Identification and diagnosis of mammographic malignant architectural distortion using a deep learning based mask regional convolutional neural network.

Background: Architectural distortion (AD) is a common imaging manifestation of breast cancer, but is also seen in benign lesions. This study aimed to construct deep learning models using mask regional convolutional neural network (Mask-RCNN) for AD identification in full-field digital mammography (FFDM) and evaluate the performance of models for malignant AD diagnosis. Methods: This retrospective diagnostic study was conducted at the Second Affiliated Hospital of Guangzhou University of Chinese Medicine between January 2011 and December 2020. Patients with AD in the breast in FFDM were included. Machine learning models for AD identification were developed using the Mask RCNN method. Receiver operating characteristics (ROC) curves, their areas under the curve (AUCs), and recall/sensitivity were used to evaluate the models. Models with the highest AUCs were selected for malignant AD diagnosis. Results: A total of 349 AD patients (190 with malignant AD) were enrolled. EfficientNetV2, EfficientNetV1, ResNext, and ResNet were developed for AD identification, with AUCs of 0.89, 0.87, 0.81 and 0.79. The AUC of EfficientNetV2 was significantly higher than EfficientNetV1 (0.89 vs. 0.78, P=0.001) for malignant AD diagnosis, and the recall/sensitivity of the EfficientNetV2 model was 0.93. Conclusion: The Mask-RCNN-based EfficientNetV2 model has a good diagnostic value for malignant AD.

Assessing whether serum ceruloplasmin promotes non-alcoholic steatohepatitis via regulating iron metabolism.

Background: Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD). The diagnostic gold standard for detecting NASH still relies upon an invasive pathological biopsy. There is, therefore, a need to identify non-invasive diagnostic markers. Oxidative stress mediates fatty liver progression to NASH. Imbalanced iron metabolism produces many reactive oxygen species (ROS). Ceruloplasmin is associated with oxidase and iron metabolism-related activities. The current study aimed to determine whether there was a correlation between ceruloplasmin levels and NASH and whether such a relationship may be associated with altered iron metabolism in NASH patients. Methods: A total of 135 NAFLD patients were enrolled in this study. A pathological biopsy confirmed that 60 of those patients had NAFLD activity scores (NAS) 5, while the remaining 75 had NAS<5. Results: Receiver operating characteristic (ROC) curves confirmed that serum ceruloplasmin and ferritin levels were predictors of NAS 5 and NAS<5, with area under the curve (AUC) values of 0.80 and 0.81, respectively. The serum ceruloplasmin levels in NAS 5 patients were significantly lower than those in NAS<5 patients (p< 0.001). Serum ceruloplasmin levels were also negatively correlated with ferritin levels. Lower serum ceruloplasmin levels were associated with more severe histopathological findings. Conclusions: Low serum ceruloplasmin and high serum ferritin are correlated with NASH. A high concentration of serum ferritin is a viable clinical biomarker of NASH, and low serum ceruloplasmin may participate in the occurrence of NASH by regulating iron load, which can be used as a non-invasive diagnostic marker of NASH.

Deep learning for screening primary osteopenia and osteoporosis using spine radiographs and patient clinical covariates in a Chinese population.

Purpose: Many high-risk osteopenia and osteoporosis patients remain undiagnosed. We proposed to construct a convolutional neural network model for screening primary osteopenia and osteoporosis based on the lumbar radiographs, and to compare the diagnostic performance of the CNN model adding the clinical covariates with the image model alone. Methods: A total of 6,908 participants were collected for analysis, including postmenopausal women and men aged 50-95 years, who performed conventional lumbar x-ray examinations and dual-energy x-ray absorptiometry (DXA) examinations within 3 months. All participants were divided into a training set, a validation set, test set 1, and test set 2 at a ratio of 8:1:1:1. The bone mineral density (BMD) values derived from DXA were applied as the reference standard. A three-class CNN model was developed to classify the patients into normal BMD, osteopenia, and osteoporosis. Moreover, we developed the models integrating the images with clinical covariates (age, gender, and BMI), and explored whether adding clinical data improves diagnostic performance over the image mode alone. The receiver operating characteristic curve analysis was performed for assessing the model performance. Results: As for classifying osteoporosis, the model based on the anteroposterior+lateral channel performed best, with the area under the curve (AUC) range from 0.909 to 0.937 in three test cohorts. The models with images alone achieved moderate sensitivity in classifying osteopenia, in which the highest AUC achieved 0.785. The performance of models integrating images with clinical data shows a slight improvement over models with anteroposterior or lateral images input alone for diagnosing osteoporosis, in which the AUC increased about 2%-4%. Regarding categorizing osteopenia and the normal BMD, the proposed models integrating images with clinical data also outperformed the models with images solely. Conclusion: The deep learning-based approach could screen osteoporosis and osteopenia based on lumbar radiographs.

An MRI-Based Radiomic Model for Individualized Prediction of Hepatocellular Carcinoma in Patients With Hepatitis B Virus-Related Cirrhosis.

Objective: To develop and validate a radiomic nomogram for individualized prediction of hepatocellular carcinoma (HCC) in HBV cirrhosis patients based on baseline magnetic resonance imaging examinations and clinical data. Methods: 364 patients with HBV cirrhosis from five hospitals were assigned to the training, internal validation, external validation-1 or external validation-2 cohort. All patients underwent baseline magnetic resonance image (MRI) scans and clinical follow-up within three-year time. Clinical risk factors and MRI-based features were extracted and analyzed. The radiomic signatures were built using the radiomics-score (Rad-score) that calculated for each patient as a linear weighted combination of selected MRI-based features. Prognostic performances of the clinical and radiomic nomograms were evaluated with Cox modeling in the training and validation cohorts. Results: Eighteen features were selected for inclusion in the Rad-score prognostic model. The radiomic signature from multi-sequence MRI yielded a concordance index (C-index) of 0.710, 0.681, 0.632 and 0.658 in the training, internal validation, external validation-1, external validation-2 cohorts, respectively. Sex and Child-Turcotte-Pugh (CTP) class were the most prognostic clinical risk factors in univariate Cox proportional hazards analyses. The radiomic combined nomogram that integrated the radiomic signature with the clinical factors yielded a C-index of 0.746, 0.710, and 0.641 in the training, internal validation, and external validation-1 cohorts, respectively, which was an improvement over either the clinical nomogram or radiomic signature alone. Conclusion: We developed an MRI-based radiomic combined nomogram with good discrimination ability for the individualized prediction of HCC in HBV cirrhosis patients within three-year time.

Effects of dyslipidemia on E antigen seroconversion of patients with chronic hepatitis B treated by nucleoside (acid) analogs.

BACKGROUND: The prevalence of dyslipidemia in China is increasing annually. Current studies suggest that dyslipidemia affects the antiviral efficacy of hepatitis C virus (HCV) therapies, while recent studies suggest that serum lipids influence the response rates of chronic hepatitis B (CHB) patients receiving PEGylated interferon-alpha (Peg IFN-α) treatment. However, the role of dyslipidemia in the efficacy of nucleoside (acid) analogues (NAs) in CHB patients remains unclear. METHODS: From January 2010 to December 2013, data from 179 treatment-naive patients with CHB who were hepatitis B e antigen (HBeAg)-positive and had visited the first affiliated hospital of Wenzhou Medical University were assessed. Of these patients, 68 were assigned to the dyslipidemia group (diagnosed with CHB complicated with dyslipidemia) and 111 to the normolipidemic group. The following 3 treatment strategies were performed for all CHB patients over a 5-year period: lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy, telbivudine (LdT) monotherapy, and entecavir (ETV) monotherapy. Serum assessments, blood biochemistry, HBV serological markers, HBV DNA before treatment and HBeAg serological conversion and virological responses at different timepoints after treatment were compared between the two groups. Measurement data were compared by τ tests and enumeration data by χ2 tests. Correlation analysis was performed using binary logistic regression analysis. RESULTS: The rates of HBeAg seroconversion in the dyslipidemia group at years 1, 2, 3, and 4 were 10.3, 13.2, 17.6, and 22.1%, respectively, which were not significantly lower than those of the normolipidemic group (11.7, 16.2, 18.0 and 33.3%; χ2 = 0.085, 0.293, 0.004, and 2.601, respectively; Ρ > 0.05). However, the rates of HBeAg seroconversion in the dyslipidemia group were significantly lower than those in the normolipidemic group at year 5 (27.9% vs. 43.2%, χ2 = 4.216, Ρ < 0.05). Univariate logistic regression analysis revealed significant differences in group, gender, PTA, ALT, AST, CR, and LDL-C between groups with and without seroconversion. Multivariate regression analysis demonstrated that dyslipidemia (OR = 1.993, Ρ = 0.038) and male gender (OR = 2.317, Ρ = 0.029) were risk factors associated with HBeAg seroconversion. CONCLUSIONS: During antiviral therapy, dyslipidemia affects HBeAg seroconversion in CHB patients treated with NAs, but does not affect the virological response.

Identification of novel hepatitis B virus therapeutic vaccine candidates derived from polymerase protein.

Hepatitis B virus (HBV) infection is a worldwide health problem with high morbidity and mortality rates. The therapeutic vaccine is a promising method of treatment, and HBV polymerase plays a vital role in viral replication. Therefore, a therapeutic vaccine that binds to HBV DNA polymerase may control HBV infection. We predicted and selected epitopes of polymerase using online databases and analysis software. We then performed molecular docking and peptide binding assays to evaluate the binding energies and affinities between polymerase epitopes and the HLA-A0201 molecule. Finally, we induced T cells from the peripheral blood mononuclear cells (PBMCs) of healthy donors using each epitope and quantified the functions of epitope-specific T cells by IFN-γELISPOT assay, T2 cell cytotoxicity assay, HepG2.2.15 cell cytotoxicity assay and HBV gene expression assays. Four epitopes (RVTGGVFLV, GLLGFAAPF, LLDDEAGPL and YMDDVVLGA) had low binding energy and two epitopes (RVTGGVFLV and GLLGFAAPF) had a high binding affinity. The T cells stimulated by two epitopes (GLLGFAAPF and HLYSHPIIL) had a greater ability to induce immune response and suppress HBV. The HBV DNA polymerase epitopes identified in this study are promising targets for designing an epitope-based therapeutic vaccine against HBV.

Brain Functional Mechanisms Determining the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation in Primary Insomnia.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective in the treatment of primary insomnia (PI); however, its efficacy varies considerably across individuals for reasons that are unclear. In order to clarify the underlying mechanisms, this study investigated the effects of taVNS on spontaneous neuronal activity and autonomic nervous system function by functional magnetic resonance imaging (fMRI) and measurement of heart rate variability (HRV), respectively, in patients with PI. Forty patients with PI were divided into effective (group A) and ineffective (group B) groups based on their response to taVNS as determined by Pittsburgh Sleep Quality Index score reduction rate (group A ≥ 25% and group B < 25%). Spontaneous neuronal activity was measured by fractional amplitude of low-frequency fluctuations (fALFF) and HRV values and was compared between the two groups as well as before vs after taVNS. We then analyzed the correlations among efficacy of taVNS for 4 weeks, the fALFF and HRV values during continuous taVNS state. The results showed that the HRV parameter values (i.e., root mean square of successive differences, percentage of adjacent NN intervals differing by >50 ms, and high frequency) of group A were higher than those of group B during continuous taVNS state. In the fMRI scan, the fALFF values of the right cerebellum, right medial superior frontal gyrus, and bilateral supplementary motor area-which belong to the sensorimotor network (SMN)-were lower in group A than in group B during continuous taVNS state. The correlation analysis revealed that the efficacy of continuous taVNS and HRV and fALFF values were interrelated. These findings demonstrate that differential regulation of the SMN by the autonomic nervous system may be responsible for inter-individual variations in the efficacy of taVNS and suggest that HRV and fALFF are potential biomarkers for predicting PI patients' response to taVNS treatment.

Development and validation of a noninvasive clinical scoring system to predict significant fibrosis in patients with nonalcoholic fatty liver disease.

BACKGROUND: The aims of this study were to identify risk factors for significant fibrosis (SF) by assessing physical and laboratory parameters and develop and validate a clinical score and nomogram for the prediction of SF in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This retrospective study included 225 patients with histologically confirmed NAFLD who were divided into two cohorts using 10-fold cross validation for model training and validation. The clinical score and nomogram were used to predict the NAFLD outcome. RESULTS: The model for predicting SF (stage ≥ 2) including the free T4/free T3 ratio, low-density lipoprotein cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), percentage of appendicular skeletal muscle mass and aspartate aminotransferase (AST) level in the training and validation cohorts yielded an area under the receiver operator characteristic curve (AUROC) of 0.79 and 0.78, respectively. The AUROC of the combined clinical score for the prediction of SF was 0.82 (95% CI, 0.75-0.89) at a cutoff value of 3 points, with a sensitivity (SE) of 77.19%, specificity (SP) of 82.88%, positive predictive value (PPV) of 63.77%, and negative predictive value (NPV) of 90.30%. The nomogram had good performance in quantitatively predicting the risk probability of SF. CONCLUSION: Our study showed that a noninvasive clinical scoring system using easily available physical and laboratory variables can identify patients with NAFLD with or without SF with a high degree of accuracy. Application of this system may decrease the need for staging liver biopsy specimens and allow early identification and intervention in these high-risk patients.

Alginate Suppresses Liver Fibrosis Through the Inhibition of Nuclear Factor-κB Signaling.

PURPOSE: Liver fibrosis (or liver scarring) is a causative factor for hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Alginate (Agn) isolated from brown algae is known to slow the proliferation of fibroblasts, through the mechanisms of these effects remain undefined. This study explored the benefits of Agn on hepatic health and its associated mechanism(s) of action in hepatic stellate cells (HSC-T6s). MATERIALS AND METHODS: To assess the effects of Agn, HSC-T6s were treated with PDGF and cell proliferation, colony formation, cell migration, cell invasiveness and apoptosis were assessed. Rat models of liver fibrosis were produced through 12-week injections of intraperitoneal (IP) carbon tetrachloride (CCl4). Rats were Agn-treated from weeks 8 to 12, and liver damage was assessed through Masson's and H & E staining. Gene expression profiles were assayed via RT-PCR, Western blot and commercial ELISA kits. RESULTS: Agn reduced the proliferation of HSC-T6s and increased apoptotic rates through the downregulation of the Bcl-2:Bax ratio. Agn also inhibited the invasion and migration of HSC-T6s, prevented ECM deposition, and reduced the occurrence of liver fibrosis in rat models. Agn also prevented IκBα and p65 phosphorylation. CONCLUSION: Agn prevents liver fibrosis through its attenuation of HSC activation and division through the suppression of NF-κB in in vitro and animal models. This highlights how the clinical use of Agn can prevent hepatic fibrosis.

Association of Serum Homocysteine Levels with Histological Severity of NAFLD.

BACKGROUND AND AIMS: Studies on the association between homocysteine and non-alcoholic fatty liver disease (NAFLD) have shown inconsistent results. Our study concerns the association of homocysteine with the histological severity of NAFLD, especially non-alcoholic steatohepatitis (NASH) and significant fibrosis (SF) after adjusting for other well-identified risk factors. METHODS: This study enrolled 289 patients with biopsy proven NAFLD. The association of homocysteine with the severe histological features was examined using multivariable logistic regression analysis and subgroup analysis. The area under curves (AUC) and Hosmer-Lemeshow goodness-of-fit test for the adjusted logistic regression models was analyzed. RESULTS: After multivariable regression analysis, homocysteine showed significant correlation with NASH (OR 0.79 95%CI: 0.69-0.89), p<0.001) and SF (OR 0.83 95%CI: 0.72-0.95, p=0.009). Spearman's correlation analysis showed homocysteine levels were inversely correlated with the grade of hepatocellular ballooning and the stage of liver fibrosis (Spearman's ρ=-0.13, p=0.033; Spearman's ρ=-0.16, p=0.007), but had no correlation with the severity of steatosis and lobular inflammation. The subgroup analyses showed that homocysteine was strongly associated with NASH in females but was weaker in males (female OR: 0.61 95%CI: 0.45-0.84; male 0.86 95%CI: 0.75-0.99), and on SF showed no significant differences in the subgroups. The models showed good discrimination for NASH (AUC 0.789, 95% CI: 0.736-0.843) and for SF (0.784 95%CI: 0.719-0.848) and calibration (Hosmer-Lemeshow goodness-of-fit test, p=0.346 for NASH; p=0.908 for SF). CONCLUSION: Elevated serum homocysteine levels are negatively associated with NASH and SF in subjects with NAFLD.

Determination of serum 25-hydroxyvitamin D status among population in southern China by a high accuracy LC-MS/MS method traced to reference measurement procedure.

OBJECTIVE: We aimed to describe the 25-hydroxyvitamin D (25(OH)D) status of southern Chinese individuals by a high-accuracy liquid chromatography tandem mass spectrometry (LC-MS/MS) method which can trace to reference measurement procedure. MATERIALS AND METHODS: From January 2018 to June 2019, a total of 4775 southern Chinese individuals were evaluated in our study. The serum levels of parathyroid hormone (PTH) were detected simultaneously in 162 cases. 25(OH)D was determined by LC-MS/MS, and PTH was detected using routine automated analysers. The distribution of the concentration, prevalence and seasonal variability of 25(OH)D in males and females of different age groups were studied. RESULTS: The mean 25(OH)D concentration in our study was 32.57 ng/mL (4.20-101.40 ng/mL). The global 25(OH)D concentration in males was higher than that in females of different age group. The prevalence of vitamin D deficiency (< 20 ng/mL) in females (16.65%) was higher than that in males (6.83%). The prevalence of vitamin D deficiency (< 20 ng/mL) was most common in winter (22.98% of all women and 15.49% of all men). 25(OH)D concentrations were higher in those from whom blood samples were collected in summer and autumn than in winter and spring. 25(OH)D2 was detected in 672 serum samples (14.07%). In addition, there was a negative correlation between the concentrations of 25(OH)D and serum PTH (r = - 0.149, P < 0.05). CONCLUSION: Our study demonstrated that the average serum 25(OH)D concentration in southern Chinese individuals was higher than that in other Chinese cohorts by a high-accuracy LC-MS/MS method. The global 25(OH)D concentration in males was higher than that in females of different ages, and the prevalence of vitamin D deficiency in females was higher than that in males. Seasonal change was an important aspect of 25(OH)D concentration in young and middle-aged people but became less relevant for that in older subjects. 25(OH)D2 detection was of minor practical significance in our study. In addition, we also found that there was a negative correlation between the serum levels of 25(OH)D and PTH in southern Chinese individuals.

Fibroblast growth factor 10 protects against particulate matter-induced airway inflammatory response through regulating inflammatory signaling and apoptosis.

Chronic respiratory disorders are some of the most frequent and severe chronic diseases in China. Epidemiological research has shown that particulate matter (PM) is a risk factor and is closely correlated to the progression of numerous respiratory diseases. Fibroblast growth factor 10 (FGF10) is a mesenchymal-epithelial signaling messenger essential for the development and environmental stability of several tissues. Nevertheless, its role in PM-induced airway inflammation remains unclear. The present study aimed to explore the mechanisms underlying the FGF10-related slowing of lung injury and inflammation in vivo and in vitro, as well as the therapeutic potential of these phenomena. Mice were intraperitoneally injected with a vehicle (PBS) or FGF10 (0.5 mg/kg) at one hour before intratracheal treatment with vehicle (PBS) or PM (4 mg/kg) for two consecutive days. Human airway epithelial BEAS-2B cells were exposed to a vehicle (PBS) or FGF10 (10 ng/ml) in vitro at one hour prior to incubation with a vehicle or PM (200 ug/ml) for 24 hours. Then, the impact on inflammatory molecules was investigated. In vivo, it was found that FGF10 diminished the inflammatory cell aggregation and reduced the apoptosis. Interestingly, in the PM group, the level of FGF10 increased in the bronchoalveolar lavage fluid (BALF). However, the pre-treatment with FGF10 markedly impaired the PM-induced increase in IL-6, IL-8, TNF-α and PGE2 levels in BALF and the cell supernatant. In conclusion, the present findings indicate that FGF10 attenuates PM-induced airway inflammation by inhibiting apoptosis and inflammation. This may be exploited for the prevention and management of PM-induced airway inflammation.

Hepatitis B virus-specific effector CD8+ T cells are an important determinant of disease prognosis: A meta-analysis.

BACKGROUND: Hepatitis B virus (HBV)-specific effector CD8+ T cells are critical for viral clearance. To determine the effects of HBV-specific effector CD8+ T cells on HBV infection, we performed a meta-analysis of the available literature. METHODS: Electronic database searches identified appropriately designed studies that detected specific CD8+ T cells in HBV-infected patients. Our main endpoints were the course of infection, seroconversion of HBV "e" antigen (HBeAg), the level of HBVDNA, and alanine aminotransferase (ALT) activity. We used a fixed/random model for analysis, according to the results of a heterogeneity test (P value of Q-squared, I2). RESULTS: Our searches found five eligible articles. Pooled estimation of the reported results showed that levels of specific CD8+ T cells were significantly higher in patients with acute hepatitis B than in patients with chronic hepatitis B (odds ratio [OR] = 76.30, 95% confidence interval [CI]: 15.37-378.70). With respect to chronic hepatitis B, patients with <107 copies/ml HBVDNA had higher levels of specific CD8+ T cells relative to patients with >107 copies/ml HBVDNA, but the difference had no statistics significance (OR: 3.89, 95% CI: 0.71-21.33). Patients with negative HBeAg or positive anti-HBeAg antibody (anti-HBe) results had significantly higher levels of specific CD8+ T cells versus patients with positive HBeAg results (OR: 5.82, 95% CI: 1.41-24.13). There were no significant associations between the levels of specific CD8+ T cells and serum ALT activity (OR = 0.86, 95% CI: 0.01-74.15). CONCLUSION: HBV-specific effector CD8+ T cells influence the disease activity in HBV-infected patients in various ways and determine prognosis by eliminating the virus. Therefore, efforts of studying HBV-specific effector CD8+ T cells focused vaccine are potentially needed.

Assessing the Ecological Effects of Water Transport to a Lake in Arid Regions: A Case Study of Qingtu Lake in Shiyang River Basin, Northwest China.

With the continuous growth of economic water consumption in arid regions, many endorheic rivers and terminal lakes have desiccated. As an important ecological engineering measure, water transport in arid regions has vital ecological significance for protecting the regional ecological environment and delaying desertification. In this study, Qingtu Lake, the terminal lake of Shiyang River, was selected to analyze the ecological effects of water transport by means of remote sensing interpretations and current year field investigations. The results demonstrated that, in July 2018, the water surface had formed and recovered to 5.68 km². Additionally, Qingtu Lake formed a spatial gradient distribution in groundwater depth. The depth increased in gradient from the waterside to the desert edge. There was a significant increase in the overall regional vegetation coverage, which mainly occurred in the water areas because of the extensive growth in Phragmitesaustralis, which reached 10.54 km² in area in 2018. Furthermore, the regional vegetation formed a gradient distribution, which transitioned from hygrophytes to xerophytes. This study can provide guidelines for the protection and restoration of lakes in arid regions.

LncRNA-MEG3 protects against ganglion cell dysplasia in congenital intestinal atresia through directly regulating miR-211-5p/GDNF axis.

Background LncRNAs are known to take part in normal brain functions and nervous system diseases. Little evidence has pointed to the dysregulation of lncRNAs in congenital intestinal atresia. We aimed to investigate the underlying molecular mechanism of congenital intestinal atresia that involves in lncRNA-MEG3. Materials and methods The expressions of LncRNA-MEG3, miR-211-5p and GDNF were determined by the qRT-PCR and Western blot assay when appropriate. The results were verified in intestinal atresia Wistar rat model and bone marrow derived stem cell (BMSCs)-derived into intestinal ganglion cells. RNA immunoprecipitation and RNA pull-down assays were performed to analyze the regulatory mechanism between MEG3 and miR-211-5p. The effects of MEG3 on the cell proliferation and apoptosis of isolated intestinal ganglion cells were detected with an MTT assay and flow cytometry, respectively. Results The expression of MEG3 was detected to be declined in congenital intestinal atresia tissues at clinic and animal levels. MEG3 promoted the differentiation of BMSCs into intestinal ganglion cells and regulated GDNF expression in retinal ganglion cells (RGC-5 cells) via targeting miR-211-5p. Hypoxia induced the apoptosis of intestinal ganglion cells via MEG3/miR-211-5p/GDNF axis. Conclusion MEG3 promoted the differentiation of BMSCs into intestinal ganglion cells and inhibited the apoptosis of intestinal ganglion cells under the exposure of hypoxia to protect against CIA injury via directly regulating miR-211-5p/GDNF axis.

Water Regime Evolution of Large Seasonal Lakes: Indicators for Characterization and an Application in Poyang Lake, China.

Impacted by ongoing climate change and anthropogenic activities, large seasonal lakes experience water regime evolution, which raises challenges for the management of water resources and environment. The water regime evolution refers to the spatial and temporal alterations in the hydrological features of lakes. Characterizing the lake water regime and its alteration may help policymakers design effective adaption strategies. Therefore, total 47 hydrological indicators were proposed, considering intra-annual fluctuations, flood and drought features, and rate and frequency of water level variations. Combined with Mann-Kendall algorithm and Sen's slope, the indicators were applied in Poyang Lake, a typically large seasonal lake in China, as a case study. The results revealed temporal and spatial variations in different hydrological indicators. The most dramatic alteration was the water level decline in October and November over the entire study phase, especially over the past 30 years. This was an urgent environmental problem that Poyang Lake faced, partially caused by the increased hydraulic gradient between southern and northern lake. It could trigger the drought occurring earlier, prolong the drought duration, and impair the wetland ecosystem. Environmental water requirements of both Poyang Lake and Yangtze River were suggested for regional sustainable development. The application in Poyang Lake showed the practicability and reliability of the indicators, which are applicable in international seasonal lakes. The series of indicators can be used in whole or in part, determined by the ecohydrological characters of a specific lake and the research objectives.

An environmental flow assessment of a river's blocking effect on a lake in a river-lake system: application in the Yangtze-Poyang system.

Hydrologic regimes are essential to riverine, lacustrine, and wetland ecosystems, and every component of a hydrologic regime has a specific ecological environmental function. In an outflow lake-river system, water levels are reduced by a reservoir constructed at the river, which interferes with the river-lake interrelationships by impairing the river's blocking effect. This increases the lake-river hydraulic gradient and accelerates the lake's drainage to the river, resulting in shrinkage of the lake and damaging environmental issues. To respond to these issues, we propose an environmental flow assessment that considers the river's blocking effect on the lake. This novel methodology consists of four steps: data preparation, assessment of the lake's environmental water level, assessment of the river's environmental water level, and environmental flow assessment. We estimated the river's environmental water level through a hydraulic correlation between the lake and the river, and found that the river's blocking effect could be sustained. The Yangtze-Poyang system was selected as a case study to illustrate the methodology's procedures and applicability. The impoundment of the Three Gorges Reservoir, during the fall retreating season, decreased the Yangtze's water level and weakened the Yangtze's blocking effect on Poyang Lake. Poyang Lake's environmental water level, which ranges from 11.71 to 15.81 m in the month of October, was used to estimate the Yangtze's environmental water level as falling in a range of 11.95 to 16.17 m, which corresponds to an environmental flow range of 16,822 to 32,371 m3/s. This study offers a solution for reservoir-induced accelerated lake drainage, which may be helpful in mitigating the negative impacts of reservoirs and sustaining natural rive-lake interactions.

TNF-α induces autophagy through ERK1/2 pathway to regulate apoptosis in neonatal necrotizing enterocolitis model cells IEC-6.

Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature neonates. Tumor necrosis factor-α (TNF-α) and autophagy are associated with the pathogenesis of NEC. This study aimed to explore whether TNF-α might regulate apoptosis in neonatal NEC model cells IEC-6 via regulation of autophagy. NEC rat model was induced by hand feeding and exposure to asphyxia/cold-stress for histologic examination. The NEC in vitro model (IEC-6/NEC cells) was established by stimulating the intestinal epithelial cell line IEC-6 with lipopolysaccharide (LPS, 100 µg/mL) for 3 h to investigate the effects of TNF-α on IEC-6 proliferation and apoptosis. In this study, NEC rats showed decreased proliferating cell nuclear antigen (PCNA) expression, increased TUNEL-positive cells, higher expression of TNF-α, p-ERK1/2, and autophagy-related proteins in rat small intestine compared with their controls. Additionally, the LPS-stimulated IEC-6/NEC cells showed a significantly decreased proliferation and increased apoptosis compared with the control cells. Furthermore, the LPS-stimulated IEC-6/NEC cells exhibited enhanced autophagy level, as evidenced by a dose-dependent increase in Beclin-1 protein expression, LC3II/LC3I ratio and accumulation of MDC-positive autophagic vacuoles. Moreover, inhibition of autophagy by wortmannin or LY294002 significantly abolished the LPS-mediated decreased proliferation and increased apoptosis of IEC-6/NEC cells. Results also showed that inhibition of ERK1/2 pathway using U0126 significantly inhibited TNF-α-induced autophagy. Furthermore, the TNF-α-mediated inhibition of IEC-6 proliferation and promotion of IEC-6 apoptosis was abolished by U0126. Our findings demonstrated that TNF-α might induce autophagy through ERK1/2 pathway to regulate apoptosis in neonatal NEC cells IEC-6. Our study enhances our understanding of neonatal NEC pathogenesis.

Detection and identification of serum protein peak at 6648 m/z as a novel indicator in breast cancer based on mass spectrometry.

Breast cancer (BC) is the second-leading cause of cancer mortality after lung cancer in women owing partly to a lack of specific and sensitive tests for early screening and monitoring. The detection of novel specific BC serum indicators for screening purposes is an essential clinical need. A total of 437 serum specimens from 310 BC patients that were divided into mining and testing sets were collected in this study. In contrast with the conventional BC indicators through receiver operating characteristic, survival and hazard function curves, and multivariate Cox regression analyses, we intended to hunt for stable protein indicators from serum specimens and identify their diagnostic and prognostic potential for BC. We identified a unique serum peptide located at 6648 Da originated from apoC-III with a validated correlation with BC tumorigenesis with confirmation in a substantive testing set and minimization of systematic bias by pre-analytical parameters. We found that the diagnostic efficacy of this peptide is better than the present conventional BC diagnostic indicators either alone or in combination with conventional indicators in distinguishing BC patients from control volunteers. Moreover, this peptide denotes a stronger prognostic factor for BC patients than conventional indicators. In light of these findings, we speculate that this peptide is a potential diagnostic and prognostic indicator and a supplement to conventional indicators in monitoring BC. The detection of this peptide located at 6648 Da in sera could enhance early screening and assessment of the postoperative survival opportunity for BC patients.

Evolution, opportunity and challenges of transboundary water and energy problems in Central Asia.

Central Asia is one of the regions that suffer the most prominent transboundary water and energy problems in the world. Effective transboundary water-energy resource management and cooperation are closely related with socioeconomic development and stability in the entire Central Asia. Similar to Central Asia, Northwest China has an arid climate and is experiencing a water shortage. It is now facing imbalanced supply-demand relations of water and energy resources. These issues in Northwest China and Central Asia pose severe challenges in the implementation of the Silk Road Economic Belt strategy. Based on the analysis of water and energy distribution characteristics in Central Asia as well as demand characteristics of different countries, the complexity of local transboundary water problems was explored by reviewing corresponding historical problems of involved countries, correlated energy issues, and the evolution of inter-country water-energy cooperation. With references to experiences and lessons of five countries, contradictions, opportunities, challenges and strategies for transboundary water-energy cooperation between China and Central Asia were discussed under the promotion of the Silk Road Economic Belt construction based on current cooperation conditions.