Publications by authors named "Li Jiang"

2,921 Publications

  • Page 1 of 1

The Validity of Neutrophil/lymphocyte Ratio as A Predictive Factor for Systemic Inflammatory Response Syndrome after Flexible Ureteroscopy Lithotripsy.

Urol J 2021 06 15. Epub 2021 Jun 15.

Department of Urology, the Second Affiliated Hospital of Chongqing Medical University, China 74#Linjiang Road, Chongqing, CN 400010.

Purpose: To explore the risk factors and predictive factors of systemic inflammatory response syndrome (SIRS) after flexible ureteroscopy (fURS) for upper urinary tract stones.

Materials And Methods: Patients experienced fURS from January 2014 to September 2019 were retrospectively analyzed, which were divided into the SIRS group and non-SIRS group. Clinical data of all patients, including gender, age, American society of anesthesia score, diabetes, etc., were collected. Univariate and multivariate logistic regression was used to determine the independent risk factors for SIRS after fURS, and the receiver operating characteristic (ROC) curve was drawn to verify the validity of results. In addition, patients from October 2019 to January 2020 were prospectively collected to verify the results.

Results: A total of 369 patients were retrospectively included. Univariate analysis showed significant differences in postoperative stone residuals (P = 0.039), preoperative neutrophil/ lymphocyte ratio (NLR) (P < 0.001), and lymphocyte/monocyte ratio (LMR) (P = 0.001) between two groups. Further, preoperative NLR and postoperative stone residuals were independent according to multivariate logistic regression analysis. The optimal cut-off value of preoperative NLR by ROC curve was 2.61, and the area under ROC curve was 77.9%. Prospective analysis based on 53 patients showed that the incidence of SIRS in patients with NLR > 2.61 was significantly higher than that in other patients. (RR = 4.932, P = 0.040).

Conclusion: Preoperative NLR can be used as a predictive factor for SIRS in patients with fURS according to our study. It may provide an evidence for clinicians to make preoperative decisions or medical plans.
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http://dx.doi.org/10.22037/uj.v18i.6570DOI Listing
June 2021

Different Responses of Soil Bacterial and Fungal Communities to 3 Years of Biochar Amendment in an Alkaline Soybean Soil.

Front Microbiol 2021 26;12:630418. Epub 2021 May 26.

Department of Bioengineering, College of Life Science, Huaibei Normal University, Huaibei, China.

Biochar as a soil amendment has been regarded as a promising way to improve soil fertility. However, the response of microbial community after biochar and biochar compound fertilizer (BCF) application has not been thoroughly elucidated. This study evaluated the changes in abundance and composition of bacterial and fungal communities using quantitative real-time PCR (qPCR) and Illumina MiSeq amplicon sequencing. The field experiment ran for 3 years and comprised five treatments: chemical fertilizer as control (CK), straw-returning combined with chemical fertilizer (CS), low biochar application combined with chemical fertilizer (LB), high biochar application combined with chemical fertilizer (HB) and BCF. The results showed that biochar amendment results no changes in the abundance and diversity of bacteria in the bulk and rhizosphere soils. However, the abundance of soil fungi was significantly increased by biochar amendment (LB and HB). LB treatment significantly increased the fungal alpha diversity, while there was no significant change under HB. Furthermore, the dominant bacterial phyla found in the samples were , , and . Biochar addition increased the relative abundance of in both bulk and rhizosphere soils. The dominant fungal phyla were , , and . The relative abundance of significantly decreased, but significantly increased in LB and HB. In addition, redundancy analysis indicated that the changes in bacterial and fungal communities are associated with soil properties such as SOC and TN, which are crucial contributors in regulating the community composition. This study is expected to provide significant theoretical and practical knowledge for the application of biochar in agricultural ecosystem.
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http://dx.doi.org/10.3389/fmicb.2021.630418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187762PMC
May 2021

Identification of an Autoantibody Against ErbB-3-Binding Protein-1 in the Sera of Patients With Chronic Hepatitis B Virus Infection.

Front Immunol 2021 25;12:640335. Epub 2021 May 25.

Department of Immunology & Institute of Immunology, Army Medical University (Third Military Medical University), Chongqing, China.

Background: Studies have shown that autoimmune response contributes to chronic hepatitis B (CHB) development.

Aim: This study aimed to identify autoantibodies in the sera of patients with CHB and to investigate the association of autoimmune response with disease severity in CHB.

Methods: Proteins from human liver carcinoma cell line HepG2 were separated by two-dimensional electrophoresis. The candidate autoantigens were recognized by serum autoantibodies from Chinese CHB patients. Immunohistochemical staining was performed to determine the hepatic expression of the autoantigen in CHB patients with different inflammatory grades. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the prevalence and the levels of serum autoantibody in CHB patients with different disease severity. Flow cytometry analysis was carried out to assess the autoreactive T cell response in the peripheral circulation of CHB patients.

Results: ErbB-3-binding protein-1 (EBP-1) was identified as an autoantigen of serum autoantibodies in CBP patients. EBP-1 protein expression was upregulated in the liver of CHB patients with high-grade hepatic inflammation. The prevalence and levels of serum anti-EBP1 IgG were significantly increased in CHB patients with severe diseases compared with those with mild or moderate diseases, but none was detectable in the healthy controls. EBP-1 peptides induced proinflammatory cytokine expression in CD4 T cells from CHB patients.

Conclusion: Our results demonstrate the presence of an autoantibody against EBP-1 in the sera as well as EBP-1-reactive T cells in the peripheral blood of CHB patient. EBP-1-induced autoimmune response is positively associated with the disease severity, suggesting that EBP-1-induced autoimmune response possibly contributes to progressive liver failure.
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http://dx.doi.org/10.3389/fimmu.2021.640335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185336PMC
May 2021

Associations between female lung cancer risk and sex steroid hormones: a systematic review and meta-analysis of the worldwide epidemiological evidence on endogenous and exogenous sex steroid hormones.

BMC Cancer 2021 Jun 10;21(1):690. Epub 2021 Jun 10.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.

Background: Published findings suggest sex differences in lung cancer risk and a potential role for sex steroid hormones. Our aim was to perform a meta-analysis to investigate the effects of sex steroid hormone exposure specifically on the risk of lung cancer in women.

Methods: The PubMed, MEDLINE, Web of Science, and EMBASE databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for female lung cancer risk associated with sex steroid hormones were calculated overall and by study design, publication year, population, and smoking status. Sensitivity analysis, publication bias, and subgroup analysis were performed.

Results: Forty-eight studies published between 1987 and 2019 were included in the study with a total of 31,592 female lung cancer cases and 1,416,320 subjects without lung cancer. Overall, higher levels of sex steroid hormones, both endogenous (OR: 0.92, 95% CI: 0.87-0.98) and exogenous (OR: 0.86, 95% CI: 0.80-0.93), significantly decreased the risk of female lung cancer by 10% (OR: 0.90, 95% CI: 0.86-0.95). The risk of lung cancer decreased more significantly with a higher level of sex steroid hormones in non-smoking women (OR: 0.88, 95% CI: 0.78-0.99) than in smoking women (OR: 0.98, 95% CI: 0.77-1.03), especially in Asia women (OR: 0.84, 95% CI: 0.74-0.96).

Conclusions: Our meta-analysis reveals an association between higher levels of sex steroid hormone exposure and the decreased risk of female lung cancer. Surveillance of sex steroid hormones might be used for identifying populations at high risk for lung cancer, especially among non-smoking women.
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http://dx.doi.org/10.1186/s12885-021-08437-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194027PMC
June 2021

Silicon/2D-material photodetectors: from near-infrared to mid-infrared.

Light Sci Appl 2021 Jun 9;10(1):123. Epub 2021 Jun 9.

State Key Laboratory for Modern Optical Instrumentation, Zhejiang Provincial Key Laboratory for Sensing Technologies, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Zijingang Campus, Hangzhou, 310058, China.

Two-dimensional materials (2DMs) have been used widely in constructing photodetectors (PDs) because of their advantages in flexible integration and ultrabroad operation wavelength range. Specifically, 2DM PDs on silicon have attracted much attention because silicon microelectronics and silicon photonics have been developed successfully for many applications. 2DM PDs meet the imperious demand of silicon photonics on low-cost, high-performance, and broadband photodetection. In this work, a review is given for the recent progresses of Si/2DM PDs working in the wavelength band from near-infrared to mid-infrared, which are attractive for many applications. The operation mechanisms and the device configurations are summarized in the first part. The waveguide-integrated PDs and the surface-illuminated PDs are then reviewed in details, respectively. The discussion and outlook for 2DM PDs on silicon are finally given.
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http://dx.doi.org/10.1038/s41377-021-00551-4DOI Listing
June 2021

Deep learning-based identification of acute ischemic core and deficit from non-contrast CT and CTA.

J Cereb Blood Flow Metab 2021 Jun 8:271678X211023660. Epub 2021 Jun 8.

Human Phenome Institute, Fudan University, Shanghai, China.

The accurate identification of irreversible infarction and salvageable tissue is important in planning the treatments for acute ischemic stroke (AIS) patients. Computed tomographic perfusion (CTP) can be used to evaluate the ischemic core and deficit, covering most of the territories of anterior circulation, but many community hospitals and primary stroke centers do not have the capability to perform CTP scan in emergency situation. This study aimed to identify AIS lesions from widely available non-contrast computed tomography (NCCT) and CT angiography (CTA) using deep learning. A total of 345AIS patients from our emergency department were included. A multi-scale 3D convolutional neural network (CNN) was used as the predictive model with inputs of NCCT, CTA, and CTA+ (8 s delay after CTA) images. An external cohort with 108 patients was included to further validate the generalization performance of the proposed model. Strong correlations with CTP-RAPID segmentations ( = 0.84 for core,  = 0.83 for deficit) were observed when NCCT, CTA, and CTA+ images were all used in the model. The diagnostic decisions according to DEFUSE3 showed high accuracy when using NCCT, CTA, and CTA+ (0.90±0.04), followed by the combination of NCCT and CTA (0.87±0.04), CTA-alone (0.76±0.06), and NCCT-alone (0.53±0.09).
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http://dx.doi.org/10.1177/0271678X211023660DOI Listing
June 2021

Neat1 decreases neuronal apoptosis after oxygen and glucose deprivation.

Neural Regen Res 2022 Jan;17(1):163-169

Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Studies have shown that downregulation of nuclear-enriched autosomal transcript 1 (Neat1) may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice. Whether Neat1 has protective or inhibitory effects on neuronal cell apoptosis after secondary brain injury remains unclear. Therefore, the effects of Neat1 on neuronal apoptosis were observed. C57BL/6 primary neurons were obtained from the cortices of newborn mice and cultured in vitro, and an oxygen and glucose deprivation cell model was established to simulate the secondary brain injury that occurs after traumatic brain injury in vitro. The level of Neat1 expression in neuronal cells was regulated by constructing a recombinant adenovirus to infect neurons, and the effects of Neat1 expression on neuronal apoptosis after oxygen and glucose deprivation were observed. The experiment was divided into four groups: the control group, without any treatment, received normal culture; the oxygen and glucose deprivation group were subjected to the oxygen and glucose deprivation model protocol; the Neat1 overexpression and Neat1 downregulation groups were treated with Neat1 expression intervention techniques and were subjected to the in oxygen and glucose deprivation protocol. The protein expression levels of neurons p53-induced death domain protein 1 (PIDD1, a pro-apoptotic protein), caspase-2 (an apoptotic priming protein), cytochrome C (a pro-apoptotic protein), and cleaved caspase-3 (an apoptotic executive protein) were measured in each group using the western blot assay. To observe changes in the intracellular distribution of cytochrome C, the expression levels of cytochrome C in the cytoplasm and mitochondria of neurons from each group were detected by western blot assay. Differences in the cell viability and apoptosis rate between groups were detected by cell-counting kit 8 assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, respectively. The results showed that the apoptosis rate, PIDD1, caspase-2, and cleaved caspase-3 expression levels significantly decreased, and cell viability significantly improved in the Neat1 overexpression group compared with the oxygen and glucose deprivation group; however, Neat1 downregulation reversed these changes. Compared with the Neat1 downregulation group, the cytosolic cytochrome C level in the Neat1 overexpression group significantly decreased, and the mitochondrial cytochrome C level significantly increased. These data indicate that Neat1 upregulation can reduce the release of cytochrome C from the mitochondria to the cytoplasm by inhibiting the PIDD1-caspase-2 pathway, reducing the activation of caspase-3, and preventing neuronal apoptosis after oxygen and glucose deprivation, which might reduce secondary brain injury after traumatic brain injury. All experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China, on December 19, 2020 (approval No. 2020-895).
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http://dx.doi.org/10.4103/1673-5374.314313DOI Listing
January 2022

Ghost spintronic THz-emitter-array microscope.

Light Sci Appl 2020 Jun 8;9(1):99. Epub 2020 Jun 8.

Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang, 621900, Sichuan, China.

Terahertz (THz) waves show great potential in nondestructive testing, biodetection and cancer imaging. Despite recent progress in THz wave near-field probes/apertures enabling raster scanning of an object's surface, an efficient, nonscanning, noninvasive, deep subdiffraction imaging technique remains challenging. Here, we demonstrate THz near-field microscopy using a reconfigurable spintronic THz emitter array (STEA) based on the computational ghost imaging principle. By illuminating an object with the reconfigurable STEA followed by computing the correlation, we can reconstruct an image of the object with deep subdiffraction resolution. By applying an external magnetic field, in-line polarization rotation of the THz wave is realized, making the fused image contrast polarization-free. Time-of-flight (TOF) measurements of coherent THz pulses further enable objects at different distances or depths to be resolved. The demonstrated ghost spintronic THz-emitter-array microscope (GHOSTEAM) is a radically novel imaging tool for THz near-field imaging, opening paradigm-shifting opportunities for nonintrusive label-free bioimaging in a broadband frequency range from 0.1 to 30 THz (namely, 3.3-1000 cm).
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http://dx.doi.org/10.1038/s41377-020-0338-4DOI Listing
June 2020

Sub-Classification of Cirrhosis Affects Surgical Outcomes for Early Hepatocellular Carcinoma Independent of Portal Hypertension.

Front Oncol 2021 20;11:671313. Epub 2021 May 20.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Severity of liver cirrhosis is distinct from clinical portal hypertension because there exist different degrees of liver cirrhosis in hepatocellular carcinoma (HCC) patients without significant clinical portal hypertension. Whether severity of cirrhosis affects surgical outcomes for HCC patients in absence of portal hypertension or not remains unclear. This study aims to analyze the effect of cirrhotic severity on surgical outcomes for HCC patients with hepatitis B virus (HBV) infection in absence of portal hypertension. This retrospective study enrolled 166 patients who underwent curative resection for a single HCC ≤5 cm in absence of portal hypertension between February 2011 and December 2013. Liver cirrhosis was sub-classified into no/mild (no/F4A) and moderate/severe (F4B/F4C) according to the Laennec scoring system. The surgical outcomes and complications were analyzed. The surgical mortality was zero in this study. Major complications were apparently higher in the F4B/F4C group than in the no/F4A group (17.0% vs 7.4%, 0.001). The 1-year, 3-year and 5-year overall survival (OS) rates were 98.5, 88.1 and 80%, respectively, in the no/F4A group, which were significantly higher than those in the F4B/F4C group (98.0, 69.2 and 54.7%, = 0.001). Microscopic vascular invasion, absence of tumor capsule and severity of liver cirrhosis were independent risk factors of surgical outcomes for HCC patients without portal hypertension. In conclusion, severity of liver cirrhosis affected surgical outcomes for early-stage HCC patients independent of portal hypertension.
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http://dx.doi.org/10.3389/fonc.2021.671313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173036PMC
May 2021

Melanotic Neuroectodermal Tumor of Infancy: A Clinicopathological and V600E Mutation Study of 11 Cases.

Front Oncol 2021 20;11:668505. Epub 2021 May 20.

Department of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China.

Purpose: To investigate the clinicopathological features and V600E mutation of melanotic neuroectodermal tumor of infancy (MNTI).

Materials And Methods: Eleven cases of MNTI diagnosed at the Department of Oral Pathology were collected. Clinicopathological characteristics were obtained from the medical records. Immunostaining was performed by immunohistochemistry (IHC). Amplification-Refractory Mutation System-qPCR (ARMS-qPCR) and Sanger Sequencing were used to detect V600E mutation.

Results: Of the 11 cases, 3 cases were female and 8 cases were male. The mean age of the first symptoms was 3.2 months (range: 1 to 6 months). Ten cases (90.9%) located in maxilla but only one (9.1%) in mandible. Most of the cases demonstrated well-defined mass with lytic bone destruction and tooth germ affecting radiologically. Histologically, MNTI was consisted of large polygonal melanin-producing epithelioid cells and small round neuroblast-like cells which arranged in irregular alveolar, tubuloglandular and fissured architecture. The epithelioid cells expressed Vim, Pan-CK, NSE and HMB45, while the smalls cells expressed Syn, NSE and scattered Vim. Most cases showed low Ki-67 index (range: <1% to 50%). None of the MNTI cases showed V600E mutation. Most cases were treated with enucleation (45.4%) or curettage (36.4%). Among the 11 cases, 6 cases had follow-up information, and 2 cases had recurrence lesions after surgery.

Conclusion: MNTI, an extremely rare tumor, mainly affects male infants with strong preference for maxilla. Distinct histopathological features and immunohistochemical profile are helpful to distinguish from other melanin-containing tumors and small round cell tumors. No V600E mutation in MNTI is detected in the present study and needs further investigations. The factors that contribute to the local recurrence of MNTI are controversial, but the close follow-up for the patients is recommended.
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http://dx.doi.org/10.3389/fonc.2021.668505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173088PMC
May 2021

Construction of a ceRNA Network and a Prognostic lncRNA Signature associated with Vascular Invasion in Hepatocellular Carcinoma based on Weighted Gene Co-Expression Network Analysis.

J Cancer 2021 5;12(13):3754-3768. Epub 2021 May 5.

Hepatic Surgery Center, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Understanding risk factors for vascular invasion (VI) is crucial for assessing the risk of recurrence and overall prognosis of hepatocellular carcinoma (HCC). This study aimed to construct a prognostic long non-coding RNA (lncRNA) signature and a ceRNA Network associated with vascular invasion in HCC. Differentially expressed genes (DEGs) of HCC patients associated with VI were identified by analyzing data from TCGA. Weighted gene co-expression network analysis (WGCNA) was used to identify associations between gene expression modules and clinical features. A VI-related prognostic lncRNA signature was then established using univariate, LASSO and multivariate Cox proportional hazards regression analyses. Based on the hub modules identified by the WGCNA, we constructed a VI-related lncRNA-miRNA-mRNA ceRNA network and screened hub lncRNAs for further research. Finally, we conducted and experiments to determine the biological roles of the identified hub gene BBOX1-AS1. The key module related to VI and OS was identified using WGCNA, after which a prognostic model consisting of eight lncRNAs was established, and verified using time-dependent receiver operating characteristic (ROC) curve analysis. BBOX1-AS1 was confirmed to be highly expressed in HCC tissues, and its expression was significantly correlated with a poor prognosis. Silencing BBOX1-AS1 significantly suppressed the proliferation, migration and invasion of HCC cells. experiments demonstrated that knocking down of BBOX1-AS1 could result in significant decrease of tumor volume and tumor weight. The VI-related lncRNA signature established in this study can be used to predict the clinical outcomes of HCC patients. In addition, we constructed a VI-related lncRNA-miRNA-mRNA ceRNA network and demonstrated that BBOX1-AS1 might be a novel biomarker associated with VI in HCC.
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http://dx.doi.org/10.7150/jca.57260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176257PMC
May 2021

MicroRNA expression profiling involved in doxorubicin-induced cardiotoxicity using high-throughput deep-sequencing analysis.

Oncol Lett 2021 Jul 26;22(1):560. Epub 2021 May 26.

Department of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China.

MicroRNAs (miRNAs/miRs) are sensitive biomarkers and endogenous repressors of gene expression by decreasing mRNA stability and interfering with mRNA translation. Despite a number of investigations revealing the dysregulation of miRNA expression associated with cardiotoxicity induced by doxorubicin (Dox), perturbation of miRNAs directly resulting from Dox at early stage in cardiomyocytes and the target gene interaction remain largely unknown. In the present study, high-throughput deep-sequencing was used to analyze changes in global miRNA expression in H9c2 cardiomyocytes exposed to 5 µg/ml Dox for 0, 12 or 24 h. Compared with the 0-h time point, the expression levels of 386 unique miRNAs were altered. Based on miRNA expression and fold-change, the target genes of 76 selected miRNAs were further analyzed using gene interaction networks and pathway enrichment analysis. These miRNAs were involved in the regulation of different pathways, whose functions included apoptosis, cell proliferation, extracellular matrix remodeling, oxidative stress and lipid metabolism. These differentially expressed miRNAs included let-7 family, miR-29b-3p, miR-378-3/5p, miR-351-3p, miR-664-3p, miR-455-3p, miR-298-3p, miR-702-5p, miR-128-1-5p, miR-671 and miR-421-5p. The present data indicated that global wide miRNA profiling in Dox-induced cardiomyocytes may provide a novel mechanistic insight into understanding Dox-induced heart failure and cardiotoxicity, as well as novel biomarkers and therapeutic targets.
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http://dx.doi.org/10.3892/ol.2021.12821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170198PMC
July 2021

Development and validation of a new prognostic score for hepatitis B virus-related acute-on-chronic liver failure.

J Hepatol 2021 Jun 3. Epub 2021 Jun 3.

Institute of Pharmaceutical Biotechnology and the First Affiliated Hospital Department of Radiation Oncology, Zhejiang University School of Medicine, Hangzhou, China; Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Zhejiang University, Hangzhou, China. Electronic address:

Background & Aims: The early prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important to decrease its high mortality. This study aims to develop a new simplified prognostic score to accurately predict the outcome of these patients.

Methods: The prospective clinical data of 2409 hospitalized patients with acute deterioration of HBV-related chronic liver disease were used to develop a new prognostic score that was validated by an external group.

Results: A total of 954 enrolled patients with HBV-ACLF were diagnosed based on the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) criteria. Six predictive factors were significantly related to the 28-day mortality and constituted a new prognostic score (=1.649×ln(international normalized ratio)+0.457×hepatic encephalopathy score+0.425×ln(neutrophil)+0.396×ln(total bilirubin)+0.576×ln(serum urea)+0.033×age). The C-indices of the new score for 28-/90-day mortality (0.826/0.809) were significantly higher than those of four other scores (COSSH-ACLFs, 0.793/0.784; CLIF-C ACLFs, 0.792/0.770; MELDs, 0.731/0.727; MELD-Nas, 0.730/0.726; all p<0.05). The prediction error rates of the new score for 28-day mortality were significantly lower than those of the COSSH-ACLFs (15.9%), CLIF-C ACLFs (16.3%), MELDs (35.3%) and MELD-Nas (35.6%). The probability density function evaluation and risk stratification of the new score also showed the highest predictive values for mortality. The external group further validated these results.

Conclusion: The new prognostic score based on six predictors without an assessment of organ failure can accurately predict and easily stratify the short-term mortality of patients with HBV-ACLF and might be used for early prognosis to decrease the high mortality.

Lay Summary: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complex syndrome with a high short-term mortality rate. We developed a simplified prognostic score for these patients based on a prospective multicentre cohort that showed the best predictive performance compared with four other generic prognostic scores (COSSH-ACLFs, CLIF-C ACLFs, MELDs and MELD-Nas).
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http://dx.doi.org/10.1016/j.jhep.2021.05.026DOI Listing
June 2021

A deep transfer learning framework for the automated assessment of corneal inflammation on in vivo confocal microscopy images.

PLoS One 2021 3;16(6):e0252653. Epub 2021 Jun 3.

Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology, Ophthalmology Department, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.

Purpose: Infiltration of activated dendritic cells and inflammatory cells in cornea represents an important marker for defining corneal inflammation. Deep transfer learning has presented a promising potential and is gaining more importance in computer assisted diagnosis. This study aimed to develop deep transfer learning models for automatic detection of activated dendritic cells and inflammatory cells using in vivo confocal microscopy images.

Methods: A total of 3453 images was used to train the models. External validation was performed on an independent test set of 558 images. A ground-truth label was assigned to each image by a panel of cornea specialists. We constructed a deep transfer learning network that consisted of a pre-trained network and an adaptation layer. In this work, five pre-trained networks were considered, namely VGG-16, ResNet-101, Inception V3, Xception, and Inception-ResNet V2. The performance of each transfer network was evaluated by calculating the area under the curve (AUC) of receiver operating characteristic, accuracy, sensitivity, specificity, and G mean.

Results: The best performance was achieved by Inception-ResNet V2 transfer model. In the validation set, the best transfer system achieved an AUC of 0.9646 (P<0.001) in identifying activated dendritic cells (accuracy, 0.9319; sensitivity, 0.8171; specificity, 0.9517; and G mean, 0.8872), and 0.9901 (P<0.001) in identifying inflammatory cells (accuracy, 0.9767; sensitivity, 0.9174; specificity, 0.9931; and G mean, 0.9545).

Conclusions: The deep transfer learning models provide a completely automated analysis of corneal inflammatory cellular components with high accuracy. The implementation of such models would greatly benefit the management of corneal diseases and reduce workloads for ophthalmologists.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252653PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174724PMC
June 2021

Transition from Bosentan to Ambrisentan in Pulmonary Arterial Hypertension: A Single-Center Prospective Study.

Int J Gen Med 2021 26;14:2101-2107. Epub 2021 May 26.

Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, People's Republic of China.

Background: Pulmonary hypertension patients experienced a high financial burden due to the high cost of drug therapy, high incidence of comorbidities and hospitalizations. Endothelin receptor antagonists (ERAs) in PAH treatment showed a high cost. While ambrisentan has been covered by medical insurance of a local government of China, there has been a drug transition from bosentan to ambrisentan in treating PAH patients. We evaluated the safety, efficacy and tolerability of ambrisentan after drug transition.

Methods: Liver and renal functions were inspected at baseline, month 1, 3 and 6. NT-proBNP, echocardiographic variables, WHO functional class (WHO-FC), 6-minute walking distance (6MWD) were measured in the baseline and month 6 to evaluate the safety and efficacy. Quality of life (QOL) scale was used in the baseline and month 6 to investigate the tolerability and quality of life of PAH patients.

Results: Among 224 PAH patients, 49 stable PAH patients meet the inclusion criteria were enrolled, among which three patients discontinued during the study. Our results showed no difference in 6-minute walking distance (6MWD) of PAH patients from baseline and month 6. The liver and renal function, N-terminal pro-brain natriuretic peptide (NT-proBNP), WHO functional class (WHO-FC) showed no difference either. For echocardiography parameters, the left ventricular end-diastolic dimension (LVEDD) of month 6 decreased. Other parameters were no significant difference from the baseline. There was no difference in the QOL scale between baseline and month 6.

Conclusion: Our results suggested that it is safe and tolerable for stable PAH patients to transition from bosentan to ambrisentan without influencing hematologic parameters or heart function.
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http://dx.doi.org/10.2147/IJGM.S304992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165300PMC
May 2021

Effect of Glycemic Gap upon Mortality in Critically Ill Patients with Diabetes.

J Diabetes Investig 2021 Jun 2. Epub 2021 Jun 2.

Department of Crtical Care Medicine, Fu Xing Hospital, Capital Medical University, 20A Fuxingmenwai Street, Xicheng District Beijing, 100038, China.

Objectives: Hyperglycemia, hypoglycemia and blood glucose fluctuation are associated with the outcomes in critically ill patients, but target of blood glucose control is debatable especially in patients with diabetes regarding to the situation of blood glucose control before admission to ICU. This study is aimed to investigate the association between glycemic gap which is calculated as the mean blood glucose level during the first 7 days after admission to ICU minus the A1C-derived average glucose and outcomes of critically ill patients with diabetes.

Method: This study undertaken in two intensive care units (ICUs) with a total of 30 beds. Patients with diabetes expected to stay for more than 24hrs were enrolled, HbA1c was tested within 3 days after admission and converted to the A1C-derived average glucose (ADAG) by the equation: ADAG = [ ( HbA1c * 28.7 ) - 46.7 ] * 18-1, arterial blood glucose measurements were fourth per day routinely during the first 7 days after admission, APACHE II score within first 24 hours, the mean blood glucose level(MGL), standard deviation(SD), and coefficient of variation(CV) during first 7 days were calculated for each person, GAPadm and GAPmean were calculated as admission blood glucose and MGL minus ADAG respectively, the incidence of moderate hypoglycemia(MH) and severe hypoglycemia(SH), total dosage of glucocorticoids and average daily dosage of insulin within 7 days, duration of renal replacement therapy(RRT), ventilator-free hours, and non-ICU stay days within 28 days were also collected. Patients enrolled were divided into survival group and nonsurvival group according to survival or not at 28-day and 1-year after admission, exploration of the relationship between parameters derived from blood glucose and mortality in critically ill patients enrolled were undergone.

Results: 502 patients were enrolled and divided into survival group (n=310) and nonsurvival group (n=192). It was shown that two groups had comparable level of HbA1c, the nonsurvivors had greater APACHE II, MGL, SD, CV, GAP , GAP , and higher hypoglycemia incidences. Less duration of ventilator-free, non-ICU stay, and longer duration of RRT were recorded in nonsurvival group, of whom received less carbohydrate intake, higher insulin daily dosage, and glucocorticoid dosage. GAP had the greatest predictive power with AUC of 0.820(95%CI: 0.781-0.850), the cut-off value was 3.60mmol/L(sensitivity 78.2% and specificity 77.3%). Patients with low GAP tended to survive longer than the high GAP group 1 year after admission.

Conclusion: Glycemic GAP between the mean level of blood glucose within first 7 days after admission to ICU and A1C-derived average glucose was independently associated with 28-day mortality of critically ill patients with diabetes, the predictive power extended to 1 year. The incidence of hypoglycemia was associated with mortality either.
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http://dx.doi.org/10.1111/jdi.13606DOI Listing
June 2021

PAK1 inhibition reduces tumor size and extends the lifespan of mice in a genetically engineered mouse model of Neurofibromatosis Type 2 (NF2).

Hum Mol Genet 2021 Jun 1. Epub 2021 Jun 1.

Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.

Neurofibromatosis Type II (NF2) is an autosomal dominant cancer predisposition syndrome in which germline haploinsufficiency at the NF2 gene confers a greatly increased propensity for tumor development arising from tissues of neural crest derived origin. NF2 encodes the tumor suppressor, Merlin, and its biochemical function is incompletely understood. One well established function of Merlin is as a negative regulator of group A serine/threonine p21 activated kinases (PAKs). In these studies we explore the role of PAK1 and its closely related paralog, PAK2, both pharmacologically and genetically, in Merlin deficient Schwann cells and in a genetically engineered mouse model (GEMM) that develops spontaneous vestibular and spinal schwannomas. We demonstrate that PAK1 and PAK2 are both hyper activated in Merlin deficient murine schwannomas. In preclinical trials, a pan Group A PAK inhibitor, FRAX-1036, transiently reduced PAK1 and PAK2 phosphorylation in vitro, but had insignificant efficacy in vivo. NVS-PAK1-1, a PAK1 selective inhibitor, had a greater but still minimal effect on our GEMM phenotype. However, genetic ablation of Pak1 but not Pak2 reduced tumor formation in our NF2 GEMM. Moreover, germline genetic deletion of Pak1 was well tolerated while conditional deletion of Pak2 in Schwann cells resulted in significant morbidity and mortality. These data support the further development of PAK1-specific small molecule inhibitors and the therapeutic targeting of PAK1 in vestibular schwannomas and argue against PAK1 and PAK2 existing as functionally redundant protein isoforms in Schwann cells.
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http://dx.doi.org/10.1093/hmg/ddab106DOI Listing
June 2021

Environmental Efficiency Assessment of Heavy Pollution Industry by Data Envelopment Analysis and Malmquist Index Analysis: Empirical Evidence from China.

Int J Environ Res Public Health 2021 May 27;18(11). Epub 2021 May 27.

School of Business, Jiangsu Normal University, Xuzhou 221116, China.

Industrial waste discharged by heavy pollution industry is one of the main causes of global environmental degradation. Research on the environmental efficiency of high-polluting industry is necessary to tackle the problem of global environmental pollution. Using panel data of 19 sub-industries in China's heavy pollution industry from 2001 to 2015, this article employs Data Envelopment Analysis (DEA) and Malmquist index (MI) to measure the environmental efficiency of heavy pollution industry from both the dynamic and static perspectives. The results show that the environmental efficiency of China's heavy pollution industry maintains an upward trend but did not reach the optimal level. The general trend shows a phased trend of increasing first and then decreasing. Besides, there are inter-industry differences in the environmental efficiency across the examined sub-industries. Based on the research findings, this article proposes a set of corresponding countermeasures to solve the global pollution problem, such as reducing energy inputs and minimizing the volumes of the main categories of emissions in high-polluting industry, as well as improving the production management in the group of high environmental efficiency and strengthening technical capabilities in the group of low environmental efficiency.
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http://dx.doi.org/10.3390/ijerph18115761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198010PMC
May 2021

Comprehensive analysis of the competing endogenous circRNA-lncRNA-miRNA-mRNA network and identification of a novel potential biomarker for hepatocellular carcinoma.

Aging (Albany NY) 2021 May 28;13. Epub 2021 May 28.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.

Background: The competing endogenous RNAs (ceRNAs) hypothesis has received increasing attention as a novel explanation for tumorigenesis and cancer progression. However, there is still a lack of comprehensive analysis of the circular RNA (circRNA)-long non-coding RNA (lncRNA)-miRNA-mRNA ceRNA network in hepatocellular carcinoma (HCC).

Methods: RNA sequencing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were employed to identify Differentially Expressed mRNAs (DEmRNAs), DElncRNAs, and DEcircRNAs between HCC and normal tissues. Candidates were identified to construct networks through a comprehensive bioinformatics strategy. A prognostic mRNA signature was established based on data from TCGA database and validated using data from the GEO database. Then, the HCC prognostic circRNA-lncRNA-miRNA-mRNA ceRNA network was established. Finally, the expression and function of an unexplored hub gene, deoxythymidylate kinase (DTYMK), was explored through data mining. The results were examined using clinical samples and experiments.

Results: We constructed a prognostic signature with seven target mRNAs by univariate, lasso and multivariate Cox regression analyses, which yielded 1, 3 and 5-year AUC values of 0.797, 0.733 and 0.721, respectively, indicating its sensitivity and specificity in the prognosis of HCC. Moreover, the prognostic signature could be validated in GSE14520. The prognostic ceRNA network of 21 circRNAs, 15 lncRNAs, 5 miRNAs, and 7 mRNAs was established according to the targeting relationship between 7 hub mRNAs and other RNAs. Our experiment results indicated that the depletion of DTYMK inhibited liver cancer cell proliferation and invasion.

Conclusions: The network revealed in this study may help comprehensively elucidate the ceRNA mechanisms driving HCC, and provide novel candidate biomarkers for evaluating the prognosis of HCC.
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http://dx.doi.org/10.18632/aging.203056DOI Listing
May 2021

Targeting fibroblast growth factor receptors to combat aggressive ependymoma.

Acta Neuropathol 2021 May 27. Epub 2021 May 27.

Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.

Ependymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN. However, the underlying molecular mechanisms and their potential as therapeutic targets have not yet been investigated in detail. Making use of transcriptomic data across 467 EPN tissues, we found that FGFR1 and FGFR3 were both widely expressed across all molecular groups. FGFR3 mRNA levels were enriched in ST-RELA showing the highest expression among EPN as well as other brain tumors. We further identified high expression levels of fibroblast growth factor 1 and 2 (FGF1, FGF2) across all EPN subtypes while FGF9 was elevated in ST-EPN. Interrogation of our EPN single-cell RNA-sequencing data revealed that FGFR3 was further enriched in cycling and progenitor-like cell populations. Corroboratively, we found FGFR3 to be predominantly expressed in radial glia cells in both mouse embryonal and human brain datasets. Moreover, we detected alternative splicing of the FGFR1/3-IIIc variant, which is known to enhance ligand affinity and FGFR signaling. Dominant-negative interruption of FGFR1/3 activation in PF-A and ST-RELA cell models demonstrated inhibition of key oncogenic pathways leading to reduced cell growth and stem cell characteristics. To explore the feasibility of therapeutically targeting FGFR, we tested a panel of FGFR inhibitors in 12 patient-derived EPN cell models revealing sensitivity in the low-micromolar to nano-molar range. Finally, we gain the first clinical evidence for the activity of the FGFR inhibitor nintedanib in the treatment of a patient with recurrent ST-RELA. Together, these preclinical and clinical data suggest FGFR inhibition as a novel and feasible approach to combat aggressive EPN.
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http://dx.doi.org/10.1007/s00401-021-02327-xDOI Listing
May 2021

Fatty acid β-oxidation promotes breast cancer stemness and metastasis via the miRNA-328-3p-CPT1A pathway.

Cancer Gene Ther 2021 May 27. Epub 2021 May 27.

Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

MicroRNAs (miRNA) have been shown to be associated with tumor diagnosis, prognosis, and therapeutic response. MiR-328-3p plays a significant role in breast cancer growth; however, its actual function and how it modulates specific biological functions is poorly understood. Here, miR-328-3p was significantly downregulated in breast cancer, especially in patients with metastasis. Mitochondrial carnitine palmitoyl transferase 1a (CPT1A) is a downstream target gene in the miR-328-3p-regulated pathway. Furthermore, the miR-328-3p/CPT1A/fatty acid β-oxidation/stemness axis was shown responsible for breast cancer metastasis. Collectively, this study revealed that miR-328-3p is a potential therapeutic target for the treatment of breast cancer patients with metastasis, and also a model for the miRNA-fatty acid β-oxidation-stemness axis, which may assist inunderstanding the cancer stem cell signaling functions of miRNA.
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http://dx.doi.org/10.1038/s41417-021-00348-yDOI Listing
May 2021

Association between pre-diagnostic serum albumin and cancer risk: Results from a prospective population-based study.

Cancer Med 2021 Jun 26;10(12):4054-4065. Epub 2021 May 26.

Department of Thoracic surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Albumin is supposed to be associated with cancer risk. However, evidence on serum albumin and cancer risk among the Chinese population is sparse. This study was conducted to evaluate the association between pre-diagnostic serum albumin and cancer risk among Chinese.

Methods: A total of 82,061 participants with baseline information on serum albumin concentration in the Kailuan cohort were recruited. Cox proportional hazards models and restricted cubic spline (RCS) analyses were used to evaluate the association between pre-diagnostic serum albumin and cancer risk.

Results: Albumin levels were inversely associated with overall cancer risk (HR [95% CI]: Q2, Q3, Q4 vs. Q1: 0.91 [0.78-1.07], 0.80 [0.70-0.92], 0.73 [0.63-0.85]), and the risk of lung, colorectal, and liver cancer (HR [95% CI]: Q4 vs. Q1: lung: 0.70 [0.52-0.95], colorectal: 0.43 [0.26-0.72], liver: 0.59 [0.36-0.95]). After excluding new cancer cases within 2 years since enrollment, a more significant association was observed for liver cancer (HR [95% CI]: Q4 vs. Q1: 0.41 [0.21-0.78]), while associations converted to nonsignificant for lung and colorectal cancer. The RCS model suggested an inverse linear association between albumin and the risk of overall cancer (p-overall < 0.0001, p-nonlinear = 0.3716) and liver cancer (p-overall = 0.0002, p-nonlinear = 0.1807).

Conclusions: Our findings suggest that pre-diagnostic serum albumin is inversely and linearly associated with cancer risk among the Chinese population. This study provides evidence that albumin may be valuable to the prediction and stratification of cancer risk in the general population. However, the biological mechanism and clinical significance remain to be elucidated. Population studies with longer follow-up time as well as experimental studies are further required.
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http://dx.doi.org/10.1002/cam4.3937DOI Listing
June 2021

The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children.

Front Pediatr 2021 10;9:676616. Epub 2021 May 10.

Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

To study the genetic and clinical characteristics of Chinese children with pathogenic proline-rich transmembrane protein 2 () gene-associated disorders. Targeted next generation sequencing (NGS) was used to identify pathogenic variations in Chinese children with epilepsy and/or kinesigenic dyskinesia. Patients with confirmed -associated disorders were monitored and their clinical data were analyzed. Forty-four patients with pathogenic variants were recruited. Thirty-five of them (79.5%) had heterozygous mutations, including 30 frameshifts, three missenses, one nonsense, and one splice site variant. The c.649dupC was the most common variant (56.8%). Eight patients (18.2%) showed whole gene deletions, and one patient (2.3%) had 16p11.2 microdeletion. Thirty-four cases (97.1%) were inherited and one case (2.9%) was . Forty patients were diagnosed with benign familial infantile epilepsy (BFIE), two patients had paroxysmal kinesigenic dyskinesia (PKD) and two had infantile convulsions and choreoathetosis (ICCA). Patients with whole gene deletions had a later remission than patients with heterozygous mutations (13.9 vs. 7.1 months, = 0.001). Forty-two patients were treated with antiseizure medications (ASMs). At last follow-up, 35 patients, including one who did not receive therapy, were asymptomatic, and one patient without ASMs died of status epilepticus at 12 months of age. One patient developed autism, and one patient showed mild developmental delay/intellectual disability. Our data suggested that patients with whole gene deletions could have more severe manifestations in -associated disorders. Conventional ASMs, especially Oxcarbazepine, showed a good treatment response.
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http://dx.doi.org/10.3389/fped.2021.676616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141857PMC
May 2021

Arabidopsis OXS3 family proteins repress ABA signaling through interactions with AFP1 in the regulation of ABI4 expression.

J Exp Bot 2021 May 25. Epub 2021 May 25.

Plant Gene Engineering Center; Chinese Academy of Sciences Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement; Guangdong Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, China.

Abscisic Acid (ABA) and the AP2/ERF-type transcription factor called ABA Insensitive 4 (ABI4) play pivotal roles in the plant growth responses to environmental stress. An analysis of seedling development in Arabidopsis ABA hypersensitive mutants suggested that OXS3, OXS3b, O3L3, O3L4, and O3L6 were negative regulators of ABI4 expression. We therefore characterized the roles of the Oxidative Stress 3 (OXS3) family members in ABA signaling. All five OXS3 family proteins were found to interact with AFP1 in yeast two hybrid assays. Seven OXS3 family members were found to interact with histone H2A.X, although OXS3b, O3L3, and O3L5 showed weaker interactions. ChIP-qPCR analysis showed that the absence of some these OXS3 family proteins was associated with increased occupancy of histone γ-H2A.X at the ABI4 promoter which also corresponded to the de-repression of ABI4 expression. Repression of ABI4 expression, however, required both AFP1 and OXS3, OXS3b or O3L6. We conclude that in the absence of stress, OXS3 family proteins regulate γ-H2A.X deposition at the ABI4 promoter and that together with AFP1, OXS3 family proteins serve to prevent an ABA-induced growth arrest by co-repressing ABI4 through decreased promoter occupancy of histone γ-H2A.X.
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http://dx.doi.org/10.1093/jxb/erab237DOI Listing
May 2021

Clinical and genetic characteristics of epilepsy of infancy with migrating focal seizures in Chinese children.

Epilepsy Res 2021 Aug 12;174:106669. Epub 2021 May 12.

Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. Electronic address:

Objective: Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare and severe developmental epileptic encephalopathy. The aim of this study was to improve our understanding of EIMFS by using phenotype-genotype correlation.

Methods: We recruited, performed clinical genetic testing, and summarized the clinical features and genetic characteristics in five patients with EIMFS in China.

Results: The five recruited patients included 2 males and 3 females. The median age of seizure onset was 2 months (range, day 3 to 3 months). All patients exhibited the characteristics of clinically migrating focal motor (tonic or clonic) seizures. Typical migrating ictal electrical patterns were found in 1 patient; the remaining four patients presented with overlapping seizures with different areas of ictal onset in differing hemispheres. All the patients had the associated variants, including KCNT1, SCN1A, SCN2A, TBC1D24 and ALG1. All patients received two or more antiseizure medications, and 1 patient became seizure-free, 1 reported >75 % seizure reduction, 2 reported >50 % seizure reduction, and 1 patient showed no improvement. Varying degrees of psychomotor developmental delays were observed in all patients.

Conclusions: The course of EIMFS could be related to the type of gene variant present, and different genes may have specific clinical features. Larger cohorts are required to elucidate such potential phenotype-genotype correlations.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106669DOI Listing
August 2021

[Development in Tissue Clearing Technology and Its Application in Neurodegenerative Diseases].

Sichuan Da Xue Xue Bao Yi Xue Ban 2021 May;52(3):350-356

The Interdisciplinary Research Center, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.

Modern tissue clearing techniques have made it possible to have high-resolution imaging of cell populations and three-dimensional reconstruction of tissue structures, and we are able to obtain more complete three-dimensional brain structures and spatial connections between the various components of brain tissues through tissue clearing techniques. Over the past decade, scientists have developed and improved a number of tissue clearing techniques that are now widely used in neuroscience research, allowing us to extract important information from complex neural networks. Moreover, tissue clearing technology also provides research tools for the stem cell therapy and neurogeneration of neurodegenerative diseases. In this paper, we reviewed the major types of existing tissue clearing techniques and their respective strengths and weaknesses. We summarized the application of these techniques in neurodegenerative disease research and their unique merits. In addition, we explored the development requirements of tissue clearing technology, improvements in the supporting equipment, and its potential to be used as research tools for stem cell therapy and regenerative medicine in the future.
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http://dx.doi.org/10.12182/20210560302DOI Listing
May 2021

Clinical characteristics and outcomes of mechanically ventilated elderly patients in intensive care units: a Chinese multicentre retrospective study.

J Thorac Dis 2021 Apr;13(4):2148-2159

Department of Critical Care Medicine, Fu Xing Hospital, Capital Medical University, Beijing, China.

Background: In recent years, the number of elderly patients receiving mechanical ventilation (MV) in intensive care units (ICUs) has increased. However, the evidence on the outcomes of elderly mechanically ventilated patients is scant in China. Our objective was to evaluate the characteristics and outcomes in elderly patients (≥65 years) receiving MV in the ICU.

Methods: We performed a multicentre retrospective study involving adult patients who were admitted to the ICU and received at least 24 hours of MV. Patients were divided into three age groups: under 65, 65-79, and ≥80 years. The primary outcome was hospital mortality. We performed univariate and multivariate logistic regression analysis to identify factors associated with hospital mortality.

Results: A total of 853 patients were analysed. Of those, 61.5% were ≥65 years of age, and 26.0% were ≥80 years of age. There were significant differences in the principal reason for MV among the three age groups (P<0.001). Advanced age was significantly associated with total duration of MV, ICU length of stay (LOS), and ICU costs (all P<0.001), but not with hospital LOS and hospital costs (P>0.05). In addition, mortality rates in the ICU, hospital, and at 60 days significantly increased with age (all P<0.001). In the age group of 80 years and older, the mortality rates were 47.7%, 49.5%, and 50.0%, respectively. Multivariate logistic regression analysis had found that age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO/FiO) ratio, total duration of MV, ICU LOS, and the decision to withhold/withdraw life-sustaining treatments were independent influence factors for mortality rates.

Conclusions: Mechanically ventilated elderly patients (≥65 years) have a higher ICU and hospital mortality, but the hospital LOS and hospital costs are similar to younger patients. Advanced age should be considered as a significant independent risk factor for hospital mortality of mechanically ventilated ICU patients.
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http://dx.doi.org/10.21037/jtd-20-2748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107518PMC
April 2021

MerTK inhibits the activation of the NLRP3 inflammasome after subarachnoid hemorrhage by inducing autophagy.

Brain Res 2021 Sep 16;1766:147525. Epub 2021 May 16.

Department of Neurosurgery, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, Zhejiang, China; Department of Neurosurgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address:

The NLR family pyrin domain-containing 3 (NLRP3) multiprotein complex is associated with neuroinflammation and poor prognosis after subarachnoid hemorrhage (SAH). Accumulating evidence shows that Mer tyrosine kinase (MerTK) alleviates inflammatory responses via a negative feedback mechanism. However, the contribution and function of MerTK in SAH remain to be determined. In this study, we explored the role of MerTK during microglial NLRP3 inflammasome activation and evaluated its contribution to the outcome of SAH in mice. Activating MerTK with growth arrest-specific 6 (Gas6) alleviated brain edema, neuronal degeneration and neurological deficits after SAH by regulating neuroinflammation. Gas6 did not change the mRNA levels of Nlrp3 or Casp1 but decreased the protein expression of NLRP3, cleaved caspase1 (p20), interleukin-1β and interleukin-18. Furthermore, Gas6 increased the expression of Beclin1, the ratio of LC3-II/LC3-I and the level of autophagic flux. Inhibiting autophagy with 3-MA reversed the inhibition of NLRP3 inflammasome activation and diminished the neuroprotective effects of Gas6. Thus, MerTK activation may exert protective effects by limiting neuroinflammation and promoting neurological recovery after SAH via autophagy induction.
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http://dx.doi.org/10.1016/j.brainres.2021.147525DOI Listing
September 2021

Differential Membrane Protein Profile in Bovine X- and Y-Sperm.

J Proteome Res 2021 06 19;20(6):3031-3042. Epub 2021 May 19.

Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture & National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

The aim of this study was to understand the molecular mechanisms behind the biological differences of X- and Y-sperm and to screen the sex-specific candidate antigen proteins for sexed semen production. To this end, we investigated differential expression of total membrane proteins of the two sperm types by using high-purity X- and Y-sperm from 20 Holstein bulls and applying the label-free proteomic technique; 1521 proteins were identified. In the X-sperm group, 8 and 23 proteins were significantly up- and down-regulated, respectively. In the X- and the Y-sperm group, 151 and 88 proteins were specifically expressed, respectively. These were overexpressed in the dynamic changes of the actin cytoskeleton, and cell senescence/apoptosis induced by the immune response, and could result in differences in the state, size, and immune sensitivity of the X-/Y-sperm membranes. The prediction of transmembrane structure, subcellular localization, and Western blotting validation results showed that the CLRN3 and SCAMP1 proteins were cell surface specific antigens of X- and Y-sperm, respectively. Our findings help explain the molecular mechanism behind the biological differences of X-/Y-sperm and lay the foundation for application of immunological methods to produce sex-sorted semen and control livestock sex. Data are available via ProteomeXchange with identifier PXD019435.
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http://dx.doi.org/10.1021/acs.jproteome.0c00358DOI Listing
June 2021

A novel nomogram to predict evident histological liver injury in patients with HBeAg-positive chronic hepatitis B virus infection.

EBioMedicine 2021 May 17;67:103389. Epub 2021 May 17.

Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China. Electronic address:

Background: HBeAg-positive chronic infection is a unique phase of chronic hepatitis B virus (HBV) infection. Current guidelines advise against starting antiviral treatment for HBeAg-positive chronic hepatitis B virus (HBV) infection patients, some data suggest treating such patients may reduce the risk of hepatocellular carcinoma. We aimed to explore whether these patients can have evident histological liver injury (EHLI), and develop a non-invasive model for identifying EHLI in such patients.

Method: We assessed whether HBeAg-positive chronic HBV infection patients can have EHLI defined by Ishak fibrosis stage ≥3 and/or histologic activity index ≥ 9 in a prospective multicenter study. Logistic and Lasso regression was used to select the optimal predictors. We used Akaike information criterion, discrimination improvement, net reclassification improvement to develop and validate models predicting EHLI risk in training cohort and two external validation cohorts.

Findings: Of these 336 patients met the inclusion criteria, 181(54%) were HBeAg-positive chronic HBV infection, of whom 60 patients (33%) had EHLI, the proportion of significant fibrosis was higher than that of significant inflammation (33% vs. 8%, P < 0.001). Age, liver stiffness measurement, ALT, alkaline phosphatase, and albumin were identified as independent predictors for EHLI and used to develop a nomogram that have been demonstrated having a good performance in predicting EHLI with AUROCs of 0.92(95%CI: 0.86-0.99) in the training cohort (n = 233) and 0.90(95%CI: 0.84-0.95) in validation cohort 1(n = 103), significant correcting current guidelines recommendations overestimating insignificant or significant histological disease. After 72-weeks entecavir treatment for HBeAg-positive chronic HBV infection patients with EHLI identified by nomogram, histological improvement occurred in 40 of 49(82%), 38(78%) had fibrosis reversal, and 35(73%) no longer had EHLI.

Interpretation: In HBeAg-positive chronic HBV infection patients, 33% has EHLI. The nomogram developed in this study can accurately identify HBeAg-positive chronic HBV infection patients with EHLI, and that responded very well to antiviral therapy.

Funding: This study was funded by the State Key Projects Specialized on Infectious Disease, Chinese Ministry of science and technology (2013ZX10005002; 2018ZX10725506), National Natural Science Foundation of China (81970525) and Beijing Key Research Project of Special Clinical Application (Z151100004015221).
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http://dx.doi.org/10.1016/j.ebiom.2021.103389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141676PMC
May 2021