Publications by authors named "Yanna Liu"

102 Publications

Development and validation of a nomogram for predicting varices needing treatment in compensated advanced chronic liver disease: A multicenter study.

Saudi J Gastroenterol 2021 Jul 29. Epub 2021 Jul 29.

CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China.

Background: Only a small proportion of patients with compensated advanced chronic liver disease (cACLD) had varices needing treatment (VNT) after recommended esophagogastroduodenoscopy (EGD) screening. We aimed to create a non-invasive nomogram based on routine tests to detect VNT in cACLD patients.

Methods: The training cohort included 162 cACLD patients undergoing EGD in a university hospital, between January 2014 and September 2019. A nomogram was developed based on the independent predictors of VNT, selected using a multivariate logistic regression analysis. Thirty-three patients from eight university hospitals were prospectively enrolled as validation cohort between December 2018 and December 2019.

Results: The prevalence of VNT was 32.7% (53/162) and 39.4% (13/33) in training and validation cohorts, respectively. The univariate analysis identified six risk factors for VNT. On the multivariate analysis, four of them, i.e., gallbladder wall thickness (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 0.98-1.56), spleen diameter (OR: 1.02; 95% CI: 1.00-1.04), platelet count (OR: 0.98; 95% CI: 0.97-0.99), and international normalized ratio (OR: 0.58; 95% CI: 0.06-5.84) were independently associated with VNT. Thus, a nomogram based on the four above - mentioned variables was developed, and showed a favorable performance for detecting VNT, with an area under receiver operating characteristic curve of 0.848 (95% CI: 0.769-0.927) in training cohort. By applying a cut-off value of 105 in validation cohort, 31.0% of EGD were safely spared with 3.4% of missed VNT.

Conclusion: A nomogram based on routine clinical parameters was developed for detecting VNT and avoiding unnecessary EGD in cACLD patients.
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http://dx.doi.org/10.4103/sjg.sjg_22_21DOI Listing
July 2021

Detachable string magnetically controlled capsule endoscopy for detecting high-risk varices in compensated advanced chronic liver disease (CHESS1801): A prospective multicenter study.

Lancet Reg Health West Pac 2021 Jan 11;6:100072. Epub 2020 Dec 11.

Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Background: Gastroesophageal varices is a serious complication of compensated advanced chronic liver disease (cACLD). Primary prophylaxis to reduce the risk of variceal hemorrhage is recommended if high-risk varices (HRV) are detected. We performed this study to compare the accuracy, patients' satisfaction and safety of detection of HRV by detachable string magnetically controlled capsule endoscopy (DS-MCCE) with esophagogastroduodenoscopy (EGD) as the reference.

Methods: We prospectively recruited participants with cACLD from 12 university hospitals (11 in China and one in the United Kingdom) between November 2018 and December 2019 (ClinicalTrials.gov, NCT03749954). All participants underwent DS-MCCE, followed by EGD within a week in a blinded fashion. Following endoscopy, and on the same day, participants were asked to fill in a satisfaction questionnaire regarding their experience.

Findings: A total of 105 eligible participants were enrolled. With EGD as the reference standard, the concordance index, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of DS-MCCE in diagnosis of HRV were 0•90 (95% confidence interval [CI]: 0•83-0•95), 92% (95% CI: 78-98%), 88% (95% CI: 78-95%), 80% (95% CI: 70-92%), 95% (95% CI: 90-100%), 7•91 (95% CI: 4•10-15•30), and 0•09 (95% CI: 0•03-0•30), respectively. The kappa score of 0•78 (95% CI: 0•65-0•90) suggested substantial agreement between DS-MCCE and EGD. Moreover, in participants undergoing EGD without sedation, the satisfaction of DS-MCCE was significantly better than that of EGD ( < 0•0001,  = 1•15 [95%CI: 0•88-1•42]). All participants confirmed the excretion of the capsule, and no adverse events occurred.

Interpretation: DS-MCCE is an accurate alternative to EGD for detecting HRV in cACLD, which is safe and associated with better satisfaction.

Funding: A full list of funding can be found in the Funding Support section.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315440PMC
January 2021

Retraction Note to: XBP1S protects cells from ER stress-induced apoptosis through Erk1/2 signaling pathway involving CHOP.

Histochem Cell Biol 2021 Jul 1. Epub 2021 Jul 1.

Department of Orthopaedic Surgery and Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA.

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http://dx.doi.org/10.1007/s00418-021-02000-0DOI Listing
July 2021

Cathepsin C aggravates neuroinflammation via promoting production of CCL2 and CXCL2 in glial cells and neurons in a cryogenic brain lesion.

Neurochem Int 2021 Sep 23;148:105107. Epub 2021 Jun 23.

Department of Anatomy, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China; National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, Liaoning, China. Electronic address:

Objective: Chemokines regulate infiltration of immune cells to brain in inflammation. Cathepsin C (CatC), a lysosomal protease, has been found to participate in neuroinflammation. However, how CatC affects chemokines expression in neuroinflammation triggered by traumatic brain injury (TBI) remains unclear. Here, we investigated the effects of CatC on chemokines and neuroinflammation in TBI.

Methods: The present study used CatC knockdown (KD) and overexpression (OE) mice to generate cryogenic brain lesion model and determined effects of CatC on expression of chemokines CCL2, CCL5 and CXCL2 and infiltration of immune cells in acute and chronic phases of the lesion. Further, cellular sources of various chemokines were demonstrated in vitro. Values were compared with wild type (WT) mice.

Results: The results found that 6 h after lesion, CatC expression,IL-1β and TNF-α mRNA and protein expression were strongly induced in the lesions; CCL2 and CXCL2 mRNA and protein expression were increased in CatC OE mice, while decreased in CatC KD mice. On the 3rd day after lesion, macrophages and neutrophils were mainly infiltrated to the lesions. Simultaneously, Iba-1+ cells in CatC OE mice were increased, while MPO + cells in CatC KD mice were decreased. In contrast, on the 28th day after lesion, a few lymphocytes were infiltrated surrounding new blood vessels. CatC OE mice showed larger volumes of scar areas, higher expression of CCL2,CXCL2,IL-1β,TNF-α,IL-6 and iNOS, as well as stronger GFAP+ and Iba-1+ signals, while CatC KD mice had reversed effects. No significant differences of CCL5 expression were found in various genotype mice. Further, in vitro study demonstrated CatC-induced expression of CCL2 were mainly derived from microglia and neurons, while CXCL2 derived from microglia and astrocytes.

Conclusion: Our data indicate that CatC aggravates neuroinflammation via promoting production of CCL2 and CXCL2 in glial cells and neurons in a cryogenic brain lesion, providing potential cellular and molecular targets for future intervention of TBI and other neuroinflammatory diseases.
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http://dx.doi.org/10.1016/j.neuint.2021.105107DOI Listing
September 2021

[Genome-wide analysis of aberrant DNA methylation patterns in iPSCs derived from patients with Down syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jun;38(6):531-535

Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200040, China.

Objective: To study the correlation between DNA methylation patterns and gene expression in Down syndrome (DS).

Methods: Induced pluripotent stem cells (iPSCs) derived from normal controls and DS patients were subjected to whole genome bisulfite sequencing and differentially methylated region (DMR) screening. Statistical analysis for chromosomal and gene element distribution were carried out for DMR. Gene ontology (GO) and enrichment-based cluster analysis were used to explore the molecular function of differentially expressed genes.

Results: A total of 1569 DMR were identified in iPSCs derived from DS patients, for which the proportion of hypermethylation in promoter regions was significantly greater than that of the genebody. No DMR enrichment was noted on chromosome 21. Hypermethylation of the promoter and genebody was predicted to be inhibitory for gene expression. Functional clustering revealed the pathways related to neurodevelopmental, stem cell pluripotency and organ size regulation to be significantly correlated with differentially methylated genes.

Conclusion: Extensive and stochastic anomalies of genome-wide DNA methylation has been discovered in iPSCs derived from DS patients, for which the pattern and molecular regulation of methylation were significantly different from those of normal controls. Above findings suggested that DNA methylation pattern may play a vital role in both the pathogenesis of neurodevelopmental disorders and other phenotypic abnormalities during early embryonic development.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200422-00294DOI Listing
June 2021

Toxicity of Tetrabromobisphenol A and Its Derivative in the Mouse Liver Following Oral Exposure at Environmentally Relevant Levels.

Environ Sci Technol 2021 06 4;55(12):8191-8202. Epub 2021 Jun 4.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

As typical brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) and its derivative TBBPA-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) are ubiquitous in various environmental compartments. However, the potential health risk posed by these compounds, especially at environmentally relevant levels, remains unclear. In this study, using adult male mice, we investigated the toxicity of orally administered TBBPA and TBBPA-BDBPE at an environmentally relevant dose (57 nmol/kg body weight). After a single exposure and daily exposure, we assessed lipid metabolism homeostasis, the transcriptome, and immune cell components in the liver. We found that the single exposure to TBBPA or TBBPA-BDBPE alone increased the number of hepatic macrophages, induced alterations in the levels of lipids, including triacylglycerol and free fatty acids, and caused transcriptome perturbation. The results from the daily administration groups showed that TBBPA and TBBPA-BDBPE both significantly increased the triacylglycerol content; however, the elevation of hepatic macrophages was observed only in the TBBPA-BDBPE treatment group. This study confirmed that environmentally relevant levels of TBBPA and TBBPA-BDBPE are toxic to the liver. Our findings revealed that dysfunction of the liver is a health concern, following exposure to BFRs, even at very low concentrations. The chronic effects induced by TBBPA and its derivatives should be further investigated.
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http://dx.doi.org/10.1021/acs.est.1c01726DOI Listing
June 2021

Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2-STAT3 pathway.

Sci Rep 2021 Jun 1;11(1):11491. Epub 2021 Jun 1.

Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China.

Severe acute pancreatitis (SAP) is often associated with pulmonary inflammation leading to acute lung injury. Daphnetin, a natural coumarin derivative, has been reported to exert anti-inflammatory effects. Here, we explored the effect and possible mechanism of daphnetin in a mouse model of SAP-associated lung injury induced by an intraperitoneal injection of L-arginine. The severity of pancreatic and lung injury is determined by histology and its score. Immunostaining of inflammatory and apoptotic cells was used to demonstrate lung tissue inflammation and apoptosis; ELISA analysis of serum and tissue cytokine levels; and western blotting and immunohistochemical staining for the activated Janus kinase 2 (JAK2)-signal transducer and activator of transcription protein 3 (STAT3) signalling pathway in lung tissues. Daphnetin pretreatment significantly reduced SAP-induced pancreatic and lung tissue damage, reduced interleukin-6 and tumour necrosis factor-α concentrations in both serum and lung tissues, reduced serum amylase and myeloperoxidase activities, and reduced macrophage (CD11b) and neutrophil (Ly6G) infiltration and cell apoptosis in the lung tissue. Moreover, SAP-induced phosphorylation of JAK2 and STAT3 in the lung tissue was also significantly diminished by the daphnetin pretreatment. These results indicated that daphnetin reduces SAP-associated lung tissue damage, likely by inhibiting the activation of JAK2-STAT3 signalling.
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http://dx.doi.org/10.1038/s41598-021-91008-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169853PMC
June 2021

Cis-acting: A pattern of lncRNAs for gene regulation in induced pluripotent stem cells from patients with Down syndrome determined by integrative analysis of lncRNA and mRNA profiling data.

Exp Ther Med 2021 Jul 2;22(1):701. Epub 2021 May 2.

Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, P.R. China.

Down syndrome (DS), caused by the trisomy of chromosome 21, is one of the common chromosomal disorders, the main clinical manifestations of which are delayed nervous development and intellectual disability. Long non-coding RNAs (lncRNAs) have critical roles in various biological processes, including cell growth, cell cycle regulation and differentiation. The roles of abnormally expressed lncRNAs have been previously reported; however, the biological functions and regulatory patterns of lncRNAs in DS have remained largely elusive. The aim of the present study was to perform a whole-genome-wide identification of lncRNAs and mRNAs associated with DS. In addition, global expression profiling analysis of DS-induced pluripotent stem cells was performed and differentially expressed (DE) lncRNAs and mRNAs were screened. Furthermore, the target genes and functions of the DE lncRNAs were predicted using Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis. The results revealed that the majority of the lncRNAs exerted functions in DS via cis-acting target genes. In addition, the results of the enrichment analysis indicated that these target genes were mainly involved in nervous and muscle development in DS. In conclusion, this integrative analysis using lncRNA and mRNA profiling provided novel insight into the pathogenesis of DS and it may promote the diagnosis and development of novel therapeutics for this disease.
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http://dx.doi.org/10.3892/etm.2021.10133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120638PMC
July 2021

Impact of variceal eradication on rebleeding and prognosis in cirrhotic patients undergoing secondary prophylaxis.

Ann Transl Med 2021 Apr;9(7):540

Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Endoscopic therapy has been widely applied to prevent variceal rebleeding, but data addressing the effect of endoscopic variceal eradication (VE) are lacking. We aimed to clarify the clinical impact of VE and reveal the long-term incidence and mortality of gastrointestinal rebleeding.

Methods: This prospective study included 228 cirrhotic patients who underwent secondary prophylaxis for variceal bleeding and achieved VE through a systematic procedure we proposed as endoscopic sequential therapy (EST). Rebleeding rates before and after VE were compared and cumulative incidence of rebleeding and mortality were calculated using the Kaplan-Meier method. A logistic regression model and P for trend were used to investigate the optimal time limit for VE.

Results: During a median (interquartile range) follow-up duration of 33.0 (23.0-48.75) months, rebleeding was identified in 28 patients (12.3%) after VE and in 27 patients (11.8%) during endoscopic sessions. The cumulative incidence of rebleeding before and after VE was 8.4% and 1.8% at 6 months, and 14.9% and 4.0% at 1 year respectively (P<0.001). The long-term incidence of all-cause/variceal rebleeding following VE was 10.4%/9.1%, and 31.5%/23.5% at 2 and 5 years respectively. Eleven patients (4.8%) died and the 5-year mortality was 9.3%. VE achieved within 6 months was associated with fewer rebleeding events compared to VE achieved after 6 months (5.5% . 20.0%, P=0.002), while logistic regression revealed an overall increasing trend in the odds ratio of rebleeding ( patients with VE time ≤6 months) for patients with 6< VE time ≤12 months and VE time >12 months (P for trend <0.001).

Conclusions: VE further reduces rebleeding based on routine endoscopic prophylaxis and improves long-term prognosis. VE within 6 months seems to be the optimal timing and should therefore be advocated.
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http://dx.doi.org/10.21037/atm-20-3401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105824PMC
April 2021

MIF inhibitor ISO-1 alleviates severe acute pancreatitis-associated acute kidney injury by suppressing the NLRP3 inflammasome signaling pathway.

Int Immunopharmacol 2021 Jul 3;96:107555. Epub 2021 Apr 3.

Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou 450052, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, China; Henan Key Laboratory of Emergency and Trauma Research Medicine, China. Electronic address:

Background: Acute kidney injury (AKI) is an important complication of severe acute pancreatitis (SAP) with a poor prognosis. The methyl ester of (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1), an inhibitor of macrophage migration inhibitory factor (MIF), has protective effects against many diseases. Our previous study confirmed MIF inhibition alleviated SAP. Here, we explored the effects of ISO-1 in an experimental mouse model of SAP-associated AKI induced by l-arginine.

Methods: Mice were randomly divided into four treatment groups (n = 6 each): control (CON), SAP, SAP + ISO-1, and ISO-1. Histopathologic examination was used to observe damage in pancreatic and renal tissues. Biochemical and enzyme-linked immunosorbent assays (ELISA) kits were used to measure the serologic indicators amylase, lipase, creatinine, uric acid, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Immunohistochemistry was used to detect protein expression of NLRP3, ASC and caspase-1, and the infiltration of myeloperoxidase (MPO)-positive neutrophils in kidney tissue. Western blotting was used to detect NLRP3, ASC and caspase-1 and IL-1β protein expression, and real-time PCR was used to measure MIF, IL-6, TNF-α, IL-1β and IL-18 mRNA levels in kidney tissue.

Results: ISO-1 treatment alleviated pathological damage in pancreatic and renal tissues, and reduced the serum levels of amylase, lipase, creatinine, uric acid, IL-6 and TNF-α. ISO-1 also reduced protein expression of NLRP3, ASC, caspase-1 and IL-1β, mRNA expression of MIF, IL-6, TNF-α, IL-1β and IL-18, and the infiltration of MPO-positive neutrophils in kidney tissue.

Conclusion: ISO-1 has a protective effect against experimental SAP-associated AKI. And the mechanism may be associated with ISO-1 inhibiting NLRP3 inflammasome signaling pathway.
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http://dx.doi.org/10.1016/j.intimp.2021.107555DOI Listing
July 2021

Compartmentalization and Excretion of 2,4,6-Tribromophenol Sulfation and Glycosylation Conjugates in Rice Plants.

Environ Sci Technol 2021 03 5;55(5):2980-2990. Epub 2021 Feb 5.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P. R. China.

The most environmentally abundant bromophenol congener, 2,4,6-tribromophenol (2,4,6-TBP, 6.06 μmol/L), was exposed to rice for 5 d both in vivo (intact seedling) and in vitro (suspension cell) to systematically characterize the fate of its sulfation and glycosylation conjugates in rice. The 2,4,6-TBP was rapidly transformed to produce 6 [rice cells (3 h)] and 8 [rice seedlings (24 h)] sulfated and glycosylated conjugates. The predominant sulfation conjugate (TP, 93.0-96.7%) and glycosylation conjugate (TP, 77.1-90.2%) were excreted into the hydroponic solution after their formation in rice roots. However, the sulfation and glycosylation conjugates presented different translocation and compartmentalization behaviors during the subsequent Phase III metabolism. Specifically, the sulfated conjugate could be vertically transported into the leaf sheath and leaf, while the glycosylation conjugates were sequestered in cell vacuoles and walls, which resulted in exclusive compartmentalization within the rice roots. These results showed the micromechanisms of the different compartmentalization behaviors of 2,4,6-TBP conjugates in Phase III metabolism. Glycosylation and sulfation of the phenolic hydroxyl groups orchestrated by plant excretion and Phase III metabolism may reduce the accumulation of 2,4,6-TBP and its conjugates in rice plants.
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http://dx.doi.org/10.1021/acs.est.0c07184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232829PMC
March 2021

Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease.

Biomolecules 2021 02 2;11(2). Epub 2021 Feb 2.

Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China.

Golgi protein 73 (GP73) is upregulated in a variety of liver diseases, yet the detailed mechanism is poorly characterized. We analyzed GP73 in a retrospective cohort including 4211 patients with chronic liver disease (CLD) or hepatocellular carcinoma (HCC). The effect of deoxycholic acid (DCA) and nuclear factor-kappa B (NF-κB) on expression and release of GP73 in Huh-7 and SMMC7721 cells were studied. A mouse study was used to confirm our findings in vivo. A positive correlation was found between serum GP73 and total bile acid (TBA) in cirrhotic patients ( = 0.540, < 0.001), higher than that in non-cirrhotic CLD ( = 0.318, < 0.001) and HCC ( = 0.353, < 0.001) patients. In Huh-7 and SMMC7721 cells, DCA upregulated the expression and release of GP73 in a dose- and time-dependent manner. After overexpressing NF-κB p65, the promoter activity, GP73 messenger RNA (mRNA) level, and supernatant GP73 level were increased. The promotion effect of DCA on GP73 release was attenuated after inhibiting the NF-κB pathway. Mutating the binding sites of NF-κB in the sequence of the GP73 promoter led to a declined promoting effect of DCA on GP73. The upregulation role of DCA in GP73 expression through the NF-κB pathway was confirmed in vivo. In addition, exposure to DCA caused disassembly of Golgi apparatus. In summary, DCA upregulates the expression and release of GP73 via activating the NF-κB pathway and destroying the Golgi structure.
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http://dx.doi.org/10.3390/biom11020205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913056PMC
February 2021

Comparison of Different Ultrasound Classification Systems of Thyroid Nodules for Identifying Malignant Potential: A Cross-sectional Study.

Clinics (Sao Paulo) 2021 20;76:e2126. Epub 2021 Jan 20.

Department of Ultrasonic, The second affiliated hospital of nanchang university, Nanchang, Jiangxi, China.

Objective: In our organization, it has been necessary in our organization to calculate the risk categories according to the American Thyroid Association (ATA), the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME), and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) classification systems for each patient, from the year 2019; these are also required to be registered in the database. This creates a barrier to medical collaboration in everyday radiological practice because using multiple rating systems can be confusing for both readers and patients. For the change in routine practice, this study aimed to compare diagnostic parameters of the ATA, AACE/ACE/AME, and ACR TIRADS classification systems for the detection of suspicious thyroid nodule(s) considering the results of fine-needle aspiration cytopathology as the reference standard.

Methods: Data on ultrasound characteristics (2,000 nodules) and fine-needle aspiration cytopathology (39 nodules) were included in the analysis. The decision making of fine-needle aspiration biopsies was evaluated from the ultrasound characteristics as per the ATA, AACE/ACE/AME, and ACR TIRADS classification systems.

Results: The ATA, AACE/ACE/AME, and ACR TIRADS recommended 26, 32, and 37 nodules for fine-needle aspiration biopsies, respectively. Considering the results of fine-needle aspiration cytopathology as the reference standard, the ATA, AACE/ACE/AME, and ACR TIRADS classification systems had 0.993, 0.996, and 0.998 sensitivity, respectively. The accuracies were 0.641, 0.795, and 0.923, respectively.

Conclusion: The ACR TIRADS classification system is less invasive and can identify suspicious nodules more accurately than that of ATA and AACE/ACE/AME.
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http://dx.doi.org/10.6061/clinics/2021/e2126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798132PMC
April 2021

The Presence of Ascites Affects the Predictive Value of HVPG on Early Rebleeding in Patients with Cirrhosis.

Gastroenterol Res Pract 2020 24;2020:1329857. Epub 2020 Nov 24.

CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou 730000, China.

Background And Aims: Gastroesophageal variceal bleeding is a serious complication of portal hypertension in cirrhotic patients and could be predicted by hepatic venous pressure gradient (HVPG). However, whether the presence of ascites affects the prognostic value of HVPG for patients with acute variceal bleeding is still unknown. This retrospective study is aimed at investigating the influence of ascites on predictive performance of HVPG for early rebleeding in cirrhotic patients with acute variceal bleeding.

Methods: In this retrospective study, a total of 148 patients with cirrhosis hospitalized for acute variceal bleeding who underwent HVPG measurement and endoscopic variceal ligation (EVL) for the prevention of rebleeding were included. The receiver operating characteristic curve (ROC) and logistical regression method were employed to analyze the predictive performance of HVPG for early rebleeding. The locally weighted scatterplot smoothing approach was adopted to assess the monotonicity between bleeding risk and HVPG.

Results: A significantly higher HVPG level was observed in patients with early rebleeding compared to patients without rebleeding in the nonascites cohort. When using HVPG to predict early rebleeding, there was a lower area under curve in the ascites cohort compared to the nonascites cohort. HVPG was recognized as a risk factor for early rebleeding by a logistic regression model only in the nonascites cohort. An overall monotonicity in the trend of change in HVPG and risk for early rebleeding was observed in the nonascites cohort solely.

Conclusion: The predictive value of HVPG for early rebleeding in patients with cirrhosis that developed acute variceal bleeding is hindered by the presence of ascites.
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http://dx.doi.org/10.1155/2020/1329857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710417PMC
November 2020

Correlation between in vitro stability and pharmacokinetics of poly(ε-caprolactone)-based micelles loaded with a photosensitizer.

J Control Release 2020 12 22;328:942-951. Epub 2020 Oct 22.

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands. Electronic address:

Polymeric micelles are extensively investigated as drug delivery systems for hydrophobic drugs including photosensitizers (PSs). In order to benefit from micelles as targeted delivery systems for PS, rather than only solubilizers, the stability and cargo retention of the (PS-loaded) micelles should be properly assessed in biologically relevant media to get insight into the essential parameters predicting their in vivo performance (i.e., pharmacokinetics). In the present study, asymmetric flow field-flow fractionation (AF4) was used to investigate the in vitro stability in human plasma of empty and meta-tetra(hydroxyphenyl)chlorin (mTHPC)-loaded dithiolane-crosslinked micelles based on poly(ɛ-caprolactone)-co-poly(1,2-dithiolane‑carbonate)-b-poly(ethylene glycol) (p(CL-co-DTC)-PEG) and non (covalently)-crosslinked micelles composed of poly(ε-caprolactone)-b-poly(ethylene glycol) (pCL-PEG). AF4 allows separation of the micelles from plasma proteins, which showed that small non (covalently)-crosslinked pCL-PEG (17 nm) and pCL-PEG (22 nm) micelles had lower stability in plasma than pCL-PEG micelles with larger size (43 nm) and higher degree of crystallinity of pCL, and had also lower stability than covalently crosslinked p(CL-DTC)-PEG and p(CL-DTC)-PEG micelles with similar small sizes (~20 nm). In addition, PS (re)distribution to specific plasma proteins was observed by AF4, giving strong indications for the (in)stability of PS-loaded micelles in plasma. Nevertheless, fluorescence spectroscopy in human plasma showed that the retention of mTHPC in non (covalently)-crosslinked but semi-crystalline pCL-PEG micelles (>8 h) was much longer than that in covalently crosslinked p(CL-DTC)-PEG micelles (~4 h). In line with this, in vivo circulation kinetics showed that pCL-PEG micelles loaded with mTHPC had significantly longer half-life values (t½-β of micelles and mTHPC was 14 and 18 h, respectively) than covalently crosslinked p(CL-DTC)-PEG micelles (t½-β of both micelles and mTHPC was ~2 h). As a consequence, long circulating pCL-PEG micelles resulted in significantly higher tumor accumulation of both the micelles and loaded mTHPC as compared to short circulating p(CL-DTC)-PEG micelles. These in vivo data were in good agreement with the in vitro stability studies. In conclusion, the present study points out that AF4 and fluorescence spectroscopy are excellent tools to evaluate the (in)stability of nanoparticles in biological media and thus predict the (in)stability of drug loaded nanoparticles after i.v. administration, which is favorable to screen promising delivery systems with reduced experimental time and costs and without excessive use of animals.
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http://dx.doi.org/10.1016/j.jconrel.2020.10.040DOI Listing
December 2020

Development and validation of a radiomics signature as a non-invasive complementary predictor of gastroesophageal varices and high-risk varices in compensated advanced chronic liver disease: A multicenter study.

J Gastroenterol Hepatol 2021 Jun 18;36(6):1562-1570. Epub 2020 Nov 18.

Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Background And Aim: Gastroesophageal varices (GEV) present in compensated advanced chronic liver disease (cACLD) and can develop into high-risk varices (HRV). The gold standard for diagnosing GEV is esophagogastroduodenoscopy (EGD). However, EGD is invasive and less tolerant. This study aimed to develop and validate radiomics signatures based on noncontrast-enhanced computed tomography (CT) images for non-invasive diagnosis of GEV and HRV in patients with cACLD.

Methods: The multicenter trial enrolled 161 patients with cACLD from six university hospitals in China between January 2015 and September 2019, who underwent both EGD and noncontrast-enhanced CT examination within 14 days prior to the endoscopy. Two radiomics signatures, termed rGEV and rHRV, respectively, were built based on CT images in a training cohort of 129 patients and validated in a prospective validation cohort of 32 patients (ClinicalTrials. gov identifier: NCT03749954).

Results: In the training cohort, both rGEV and rHRV exhibited high discriminative abilities on determining the existence of GEV and HRV with the area under receiver operating characteristic curve (AUC) of 0.941 (95% confidence interval [CI] 0.904-0.978) and 0.836 (95% CI 0.766-0.905), respectively. In validation cohort, rGEV and rHRV showed high discriminative abilities with AUCs of 0.871 (95% CI 0.739-1.000) and 0.831 (95% CI 0.685-0.978), respectively.

Conclusions: This study demonstrated that rGEV and rHRV could serve as the satisfying auxiliary parameters for detection of GEV and HRV with good diagnostic performance.
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http://dx.doi.org/10.1111/jgh.15306DOI Listing
June 2021

Genome-wide profiling of BK polyomavirus integration in bladder cancer of kidney transplant recipients reveals mechanisms of the integration at the nucleotide level.

Oncogene 2021 01 13;40(1):46-54. Epub 2020 Oct 13.

Division of Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Chronic BK polyomavirus (BKPyV) infection is recognized as a potential oncogenic factor of urothelial carcinoma (UC) in renal transplant recipients. Recent studies have reported a positive correlation among BKPyV integration, persistent overexpression of viral large T antigen (TAg), and malignancy, yet little is known about the specific integration mechanisms and the impacts of viral integration. Here, we performed whole-genome sequencing (WGS) and viral capture-based sequencing on high-grade immunohistochemically TAg-positive UCs in two renal transplant recipients. A total of 181 integration sites, including the three found by WGS, were identified by viral capture-based sequencing, indicating its enhanced sensitivity and ability in identifying low-read integration sites in subpopulations of the tumor cells. The microhomologies between human and BKPyV genomes were significantly enriched in the flanking regions of 84.5% the integration sites, with a median length of 7 bp. Notably, 75 human genes formed fusion sequences due to viral insertional integration. Among them, the expression of 15 genes were statistically associated with UC based on GEO2R expression analysis. Our results indicated a multisite and multifragment linear integration pattern and a potential microhomology or nonhomologous end joining integration mechanism at the single-nucleotide level. We put forward a potential selection mechanism driven by immunity and centered on viral integration in the carcinogenesis of BKPyV.
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http://dx.doi.org/10.1038/s41388-020-01502-wDOI Listing
January 2021

Nontarget analysis reveals gut microbiome-dependent differences in the fecal PCB metabolite profiles of germ-free and conventional mice.

Environ Pollut 2021 Jan 25;268(Pt A):115726. Epub 2020 Sep 25.

Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA, 52242-5000, USA. Electronic address:

Mammalian polychlorinated biphenyl (PCB) metabolism has not been systematically explored with nontarget high-resolution mass spectrometry (Nt-HRMS). Here we investigated the importance of the gut microbiome in PCB biotransformation by Nt-HRMS analysis of feces from conventional (CV) and germ-free (GF) adult female mice exposed to a single oral dose of an environmental PCB mixture (6 mg/kg or 30 mg/kg in corn oil). Feces were collected for 24 h after PCB administration, PCB metabolites were extracted from pooled samples, and the extracts were analyzed by Nt-HRMS. Twelve classes of PCB metabolites were detected in the feces from CV mice, including PCB sulfates, hydroxylated PCB sulfates (OH-PCB sulfates), PCB sulfonates, and hydroxylated methyl sulfone PCBs (OH-MeSO-PCBs) reported previously. We also observed eight additional PCB metabolite classes that were tentatively identified as hydroxylated PCBs (OH-PCBs), dihydroxylated PCBs (DiOH-PCBs), monomethoxylated dihydroxylated PCBs (MeO-OH-PCBs), methoxylated PCB sulfates (MeO-PCB sulfates), mono-to tetra-hydroxylated PCB quinones ((OH)-quinones, x = 1-4), and hydroxylated polychlorinated benzofurans (OH-PCDF). Most metabolite classes were also detected in the feces from GF mice, except for MeO-OH-PCBs, OH-MeSO-PCBs, and OH-PCDFs. Semi-quantitative analyses demonstrate that relative PCB metabolite levels increased with increasing dose and were higher in CV than GF mice, except for PCB sulfates and MeO-PCB sulfates, which were higher in GF mice. These findings demonstrate that the gut microbiome plays a direct or indirect role in the absorption, distribution, metabolism, or excretion of PCB metabolites, which in turn may affect toxic outcomes following PCB exposure.
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http://dx.doi.org/10.1016/j.envpol.2020.115726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746632PMC
January 2021

Origins and Evolution of Cuticle Biosynthetic Machinery in Land Plants.

Plant Physiol 2020 12 15;184(4):1998-2010. Epub 2020 Sep 15.

College of Life Sciences, Qingdao University, Qingdao 266071, China

The aerial epidermis of land plants is covered with a hydrophobic cuticle that protects the plant against environmental stresses. Although the mechanisms of cuticle biosynthesis have been extensively studied in model plants, particularly in seed plants, the origins and evolution of cuticle biosynthesis are not well understood. In this study, we performed a comparative genomic analysis of core components that mediate cuticle biosynthesis and characterized the chemical compositions and physiological parameters of cuticles from a broad set of embryophytes. Phylogenomic analysis revealed that the cuticle biosynthetic machinery originated in the last common ancestor of embryophytes. Coexpansion and coordinated expression are evident in core genes involved in the biosynthesis of two major cuticle components: the polymer cutin and cuticular waxes. Multispecies analyses of cuticle chemistry and physiology further revealed higher loads of both cutin and cuticular waxes in seed plants than in bryophytes as well as greater proportions of dihydroxy and trihydroxy acids, dicarboxylic acids, very-long-chain alkanes, and >C28 lipophilic compounds. This can be associated with land colonization and the formation of cuticles with enhanced hydrophobicity and moisture retention capacity. These findings provide insights into the evolution of plant cuticle biosynthetic mechanisms.
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http://dx.doi.org/10.1104/pp.20.00913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723097PMC
December 2020

[Application of immunosuppressants in patients with autosomal dominant polycystic kidney disease after kidney transplantation].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Apr;40(4):538-543

Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Objective: To investigate the optimal dose range of immunosuppressants in patients with autosomal dominant polycystic kidney disease (ADPKD) after renal transplantation.

Methods: A cohort of 68 patients with ADPKD who received their first renal transplantation between March, 2000 and January, 2018 in our institute were retrospectively analyzed, with 68 non-ADPKD renal transplant recipients matched for gender, age and date of transplant as the control group. We analyzed the differences in patient and renal survival rates, postoperative complications and concentrations of immunosuppressive agents between the two groups at different time points within 1 year after kidney transplantation. The concentrations of the immunosuppressants were also compared between the ADPKD patients with urinary tract infections (UTI) and those without UTI after the transplantation.

Results: The recipients with ADPKD and the control recipients showed no significantly difference in the overall 1-, 5-, and 10- year patient survival rates (96.6% 96.0%, 94.1% 93.9%, and 90.6% 93.9%, respectively; > 0.05), 1-, 5-, and 10-year graft survival rates (95.2% 96.0%, 90.8% 87.2%, and 79.0% 82.3%, respectively; > 0.05), or the incidences of other post- transplant complications including acute rejection, gastrointestinal symptoms, cardiovascular events, pneumonia, and neoplasms ( > 0.05). The plasma concentrations of both tacrolimus and mycophenolate mofetil (MPA) in ADPKD group were significantly lower than those in the control group at 9 months after operation ( < 0.05). The incidence of UTI was significantly higher in ADPKD patients than in the control group ( < 0.05). In patients with ADPKD, those with UTI after transplantation had a significantly higher MPA plasma concentration ( < 0.05).

Conclusions: In patients with ADPKD after renal transplant, a higher dose of MPA is associated with a increased risk of UTI, and their plasma concentrations of immunosuppressants for long-term maintenance of immunosuppression regimen can be lower than those in other kidney transplantation recipients.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.04.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225103PMC
April 2020

Dithiolane-Crosslinked Poly(ε-caprolactone)-Based Micelles: Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties.

Macromolecules 2020 Aug 3;53(16):7009-7024. Epub 2020 Aug 3.

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The Netherlands.

Dithiolanes are used to obtain dynamic and reversible crosslinks between polymer chains. Copolymers of two different dithiolane-containing cyclic carbonate monomers and ε-caprolactone (CL) were synthesized by ring-opening polymerization using a methoxy-poly(ethylene glycol) (mPEG) initiator and different catalysts (diphenyl phosphate (DPP), methanesulfonic acid (MSA), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), or Sn(Oct)). Each catalyst required a different temperature, which had a pronounced influence on the reactivity ratio of the monomers and occurrence of transesterification reactions and, therefore, the monomer sequence. Self-crosslinkable copolymers were obtained when the dithiolane units were connected closely to the polymer backbone, whereas the presence of a linker unit between the dithiolane and the backbone prevented self-crosslinking. The former amphiphilic PEGylated block copolymers formed micelles by nanoprecipitation in the aqueous environment and crosslinked spontaneously by disulfide exchange during subsequent dialysis. These dithiolane-crosslinked micelles showed reduction-responsive dissociation in the presence of 10 mM glutathione, making them promising drug delivery systems for the intracellularly triggered cargo release.
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http://dx.doi.org/10.1021/acs.macromol.0c01031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458473PMC
August 2020

Viral integration in BK polyomavirus-associated urothelial carcinoma in renal transplant recipients: multistage carcinogenesis revealed by next-generation virome capture sequencing.

Oncogene 2020 08 28;39(35):5734-5742. Epub 2020 Jul 28.

Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou, China.

BK polyomavirus (BKPyV)-associated cancer after transplantation has gained increasing attention. However, the role of BKPyV integration on oncogenesis is still unclear. In this study, next-generation virome capture sequencing of primary and metastatic tumors were performed in three patients with BKPyV-associated urothelial carcinoma after renal transplantation. As a result, a total of 332 viral integration sites were identified in the six tumors. Integration of BKPyV in both primary and metastatic tumors followed the mechanism of microhomology-mediated end joining mostly, since microhomologies between human and BKPyV genomes were significantly enriched in flanking regions of 84% of the integration sites. Viral DNA breakpoints were nonrandom and tended to assemble in large T gene, small T gene and viral protein 2 gene. There were three, one and one consensus integration sites between the primary and metastatic tumors, which affected LINC01924, eIF3c, and NEIL2 genes in the three cases respectively. Thus, we concluded that integration of BKPyV was a continuous process occurring in both primary and metastatic tumors, generating heterogenous tumor cell populations. Through this ongoing process, certain cell populations might have gained growth advantage or metastatic potential, as a result of viral integration either affecting the cellular genes where the viral DNA integrated to or altering the expression or function of the viral genes.
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http://dx.doi.org/10.1038/s41388-020-01398-6DOI Listing
August 2020

Risk factors of embolism for the cardiac myxoma patients: a systematic review and metanalysis.

BMC Cardiovasc Disord 2020 07 25;20(1):348. Epub 2020 Jul 25.

Department of Ultrasound, The Second Affiliated Hospital of Nanchang University, Minde Road No.1, Nanchang, 330006, Jiangxi, China.

Background: The risk factors contributing to embolism in cardiac myxoma (CM) are yet controversial. This systematic review and meta-analysis aimed to clarify the risk factors of embolism for the CM patients.

Methods: PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wan Fang, and Wei Pu databases were searched from inception to June 2019. Statistical analysis was conducted using Stata version 14.0. The pooled odds ratio or mean difference with 95% confidence interval was estimated for each risk factor.

Results: Herein, 12 studies, encompassing 1814 patients, were included. The pooled results suggested that New York Heart Association (NYHA) class I/II (P < 0.01), hypertension (P = 0.03), irregular tumor surface (P < 0.01), tumor in atypical location (P = 0.01), narrow base of tumor (P < 0.01), and increased fibrinogen (FIB) (P < 0.01) are significant risk factors of embolism in CM patients. However, sex, age, body mass index, smoking, left ventricular ejection fraction, diabetes, hyperlipidemia, atrial fibrillation, valvular heart disease, coronary heart disease, tumor size, platelet count, white blood cells, and hemoglobin were not associated with embolism (all P > 0.05).

Conclusions: NYHA class (I/II), hypertension, irregular tumor surface, atypical tumor location, the narrow base of tumor, and increased FIB were significant risk factors of embolism in CM patients. For CM patients with these factors, early surgery might be beneficial to prevent embolism.
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http://dx.doi.org/10.1186/s12872-020-01631-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382866PMC
July 2020

Hepatic venous pressure gradient-guided laparoscopic splenectomy and pericardial devascularisation versus endoscopic therapy for secondary prophylaxis for variceal rebleeding in portal hypertension (CHESS1803): study protocol of a multicenter randomised controlled trial in China.

BMJ Open 2020 06 23;10(6):e030960. Epub 2020 Jun 23.

CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China

Introduction: Gastro-oesophageal variceal bleeding is one of the most common and severe complications with high mortality in cirrhotic patients who developed portal hypertension. Hepatic venous pressure gradient (HVPG) is a globally recommended golden standard for the portal pressure assessment and an HVPG ≥16 mm Hg indicates a higher risk of death and rebleeding. This study aims to compare the effectiveness and safety of splenectomy and pericardial devascularisation (laparoscopic therapy) plus propranolol and endoscopic therapy plus propranolol for variceal rebleeding in cirrhotic patients with HVPG between 16 and 20 mm Hg.

Methods And Analysis: This is a multicenter, randomised, controlled clinical trial. Participants will be 1:1 assigned randomly into either laparoscopic or endoscopic groups. Forty participants whose transjugular HVPG lies between 16 and 20 mm Hg with a history of gastro-oesophageal variceal bleeding will be recruited from three sites in China. Participants will receive either endoscopic therapy plus propranolol or laparoscopic therapy plus propranolol. The primary outcome measure will be the occurrence of gastro-oesophageal variceal rebleeding. Secondary outcome measures will include overall survival, occurrence of hepatocellular carcinoma, the occurrence of venous thrombosis, the occurrence of adverse events, quality of life and tolerability of treatment. Outcome measures will be evaluated at baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks and 60 weeks. Multivariate COX regression model will be introduced for analyses of occurrence data and Kaplan-Meier analysis with the log-rank test for intergroup comparison.

Ethics And Dissemination: Ethical approval was obtained from all three participating sites. Primary and secondary outcome data will be submitted for publication in peer-reviewed journals and widely disseminated.

Trial Registration Number: NCT03783065; Pre-results.

Trial Status: Recruitment for this study started in December 2018 while the first participant was randomised in January 2019. Recruitment is estimated to stop in October 2019.
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http://dx.doi.org/10.1136/bmjopen-2019-030960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312451PMC
June 2020

RING finger ubiquitin E3 ligase gene TaSDIR1-4A contributes to determination of grain size in common wheat.

J Exp Bot 2020 09;71(18):5377-5388

National Key Facility for Crop Gene Resources and Genetic Improvement/Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Salt and drought-induced RING finger1 (SDIR1) is a RING-type E3 ubiquitin ligase that plays a key role in ABA-mediated responses to salinity and drought stress via the ubiquitination pathway in some plant species. However, its function in wheat (Triticum aestivum) is unknown. Here, we isolated a SDIR1 member in wheat, TaSDIR1-4A, and characterized its E3 ubiquitin ligase activity. DNA polymorphism assays showed the presence of two nucleotide variation sites in the promoter region of TaSDIR1-4A, leading to the detection of the haplotypes Hap-4A-1 and Hap-4A-2 in wheat populations. Association analysis showed that TaSDIR1-4A haplotypes were associated with 1000-grain weight (TGW) across a variety of different environments, including well-watered and heat-stress conditions. Genotypes with Hap-4A-2 had higher TGW than those with Hap-4A-1. Phenotypes in both gene-silenced wheat and transgenic Arabidopsis showed that TaSDIR1-4A was a negative regulator of grain size. Gene expression assays indicated that TaSDIR1-4A was most highly expressed in flag leaves, and expression was higher in Hap-4A-1 accessions than in Hap-4A-2 accessions. The difference might be attributable to the fact that TaERF3 (ethylene response factor) can act as a transcriptional repressor of TaSDIR1-4A in Hap-4A-2 but not in Hap-4A-1. Examination of modern wheat varieties shows that the favorable haplotype has been positively selected in breeding programs in China. The functional marker for TaSDIR1-4A developed in this study should be helpful for future wheat breeding.
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http://dx.doi.org/10.1093/jxb/eraa271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501821PMC
September 2020

Significance of gastrointestinal tract in the therapeutic mechanisms of exercise in depression: Synchronism between brain and intestine through GBA.

Prog Neuropsychopharmacol Biol Psychiatry 2020 12 20;103:109971. Epub 2020 May 20.

Department of Anatomy, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China; National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, Liaoning, China. Electronic address:

Researchers have made considerable progress in elucidating psychological and exercise correlates of major depressive disorder (MDD). However, as the largest immune organ, far less is known about the role of gastrointestinal (GI) tract in the therapeutic mechanisms of exercise in MDD. In addition to the sites of the digestive tract that absorb nutrients, the GI tract also serves as a protective barrier against organisms. Inflammation and other consequences caused by disrupted GI barrier integrity are considered to be one of the mechanisms of depression, and the gut-brain axis (GBA) plays a critical role in this process. In this work, we observed the depression-like behaviors, intestinal barrier, central and peripheral inflammation, and related neurotransmitters through exercise intervention in the chronic unpredictable mild stress (CUMS) model, aiming to clarify the mechanisms of exercise to improve depression through GBA. Our results revealed that, following increased expressions of pro-inflammatory factors in intestine of CUMS mice, the levels of pro-inflammatory factors were all significantly raised in serum and brain simultaneously. Further, glial cells were activated in visceral nervous system and its related brain regions at the same time, accompanied by lower expression of occludin in CUMS mice. Importantly, our findings provide the first evidence that eight weeks of running exercise effectively inhibited neuro-immune interactions along gut-brain-axis and contributed obvious improvement of intestinal epithelial barrier (IEB). Finally, multivariate analysis putatively highlighted the role of exercise-induced IEB protection on depression treatment. We hope that our findings could warrant further study of therapeutic mechanisms of exercise in depression, specifically in disentangling the roles of intestinal function and IEB protection, and for developing more targeted clinical depression interventions.
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http://dx.doi.org/10.1016/j.pnpbp.2020.109971DOI Listing
December 2020

Clinical course of COVID-19 in patients with pre-existing decompensated cirrhosis: initial report from China.

Hepatol Int 2020 Jul 22;14(4):478-482. Epub 2020 May 22.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Background: The clinical characteristics and disease course in COVID-19 patients with pre-existing decompensated cirrhosis has not been described so far.

Methods: In this case series, we report three patients with confirmed COVID-19 and pre-existing decompensated cirrhosis from three hospitals in Hubei, the epicenter of the outbreak in China.

Result: Patient 1 was a 53-year-old man with hepatitis B virus-related cirrhosis, portal hypertension, and ascites. Though receiving intensive support, he died of irreversible multiple organ dysfunction syndrome 48 days after the onset of the illness. Patient 2 was a 75-year-old woman with a history of schistosomiasis-related cirrhosis, portal hypertension, and ascites. Her family members requested that invasive rescue measures not be undertaken, and she died of acute respiratory distress syndrome 40 days after presenting with COVID-19 infection. Patient 3 was an 87-year-old man with alcohol-related cirrhosis, portal hypertension, and esophageal variceal hemorrhage. He was discharged from the hospital 29 days after illness onset.

Conclusion: The case series raise the possibility that decompensated cirrhosis may be a risk factor for a poor outcome in patients with COVID-19.
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http://dx.doi.org/10.1007/s12072-020-10051-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242176PMC
July 2020

MIF inhibitor, ISO-1, attenuates human pancreatic cancer cell proliferation, migration and invasion in vitro, and suppresses xenograft tumour growth in vivo.

Sci Rep 2020 04 21;10(1):6741. Epub 2020 Apr 21.

Department of Emergency, the First Affiliated Hospital of Zhengzhou University, Henan, 450052, China.

This study sought to investigate the biological effects of specific MIF inhibitor, ISO-1, on the proliferation, migration and invasion of PANC-1 human pancreatic cells in vitro, and on tumour growth in a xenograft tumour model in vivo. The effect of ISO-1 on PANC-1 cell proliferation was examined using CCK-8 cell proliferation assay. The effect of ISO-1 on collective cell migration and recolonization of PANC-1 cells was evaluated using the cell-wound closure migration assay. The effect of ISO-1 on the migration and invasion of individual PANC-1 cells in a 3-dimensional environment in response to a chemo-attractant was investigated through the use of Transwell migration/invasion assays. Quantitative real time PCR and western blot analyses were employed to investigate the effects of ISO-1 on MIF, NF-κB p65 and TNF-α mRNA and protein expression respectively. Finally, a xenograft tumor model in BALB/c nude mice were used to assess the in vivo effects of ISO-1 on PANC-1-induced tumor growth. We found high expression of MIF in pancreatic cancer tissues. We demonstrated that ISO-1 exerts anti-cancer effects on PANC-1 cell proliferation, migration and invasion in vitro, and inhibited PANC-1 cell-induced tumour growth in xenograft mice in vivo. Our data suggests that ISO-1 and its derivative may have potential therapeutic applications in pancreatic cancer.
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http://dx.doi.org/10.1038/s41598-020-63778-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174354PMC
April 2020

π-π-Stacked Poly(ε-caprolactone)--poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy.

Pharmaceutics 2020 Apr 9;12(4). Epub 2020 Apr 9.

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3508 TB Utrecht, The Netherlands.

To improve the in vivo stability of poly(-caprolactone)-b-poly(ethylene glycol) (PCL-PEG)-based micelles and cargo retention by π-π stacking interactions, pendant aromatic rings were introduced by copolymerization of -caprolactone with benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate (TMC-Bz). It was shown that the incorporation of aromatic rings yielded smaller micelles (18-30 nm) with better colloidal stability in PBS than micelles without aromatic groups. The circulation time of i.v. injected micelles containing multiple pendant aromatic groups was longer (t½-α: ~0.7 h; t½-β: 2.9 h) than that of micelles with a single terminal aromatic group (t½ < 0.3 h). In addition, the in vitro partitioning of the encapsulated photosensitizer (meta-tetra(hydroxyphenyl)chlorin, mTHPC) between micelles and human plasma was favored towards micelles for those that contained the pendant aromatic groups. However, this was not sufficient to fully retain mTHPC in the micelles in vivo, as indicated by similar biodistribution patterns of micellar mTHPC compared to free mTHPC, and unequal biodistribution patterns of mTHPC and the host micelles. Our study points out that more detailed in vitro methods are necessary to more reliably predict in vivo outcomes. Furthermore, additional measures beyond π-π stacking are needed to stably incorporate mTHPC in micelles in order to benefit from the use of micelles as targeted delivery systems.
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http://dx.doi.org/10.3390/pharmaceutics12040338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238042PMC
April 2020
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