Publications by authors named "Ming Kong"

233 Publications

Influence of phosphorus on the NH-SCR performance of CeO-TiO catalyst for NO removal from co-incineration flue gas of domestic waste and municipal sludge.

J Colloid Interface Sci 2021 Nov 15. Epub 2021 Nov 15.

Research Center for Atmospheric Environment, Key Laboratory of Reservoir Aquatic Environment of CAS, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, PR China; College of Resources and Environment, Chongqing School, University of Chinese Academy of Sciences (UCAS Chongqing), Chongqing 400714, PR China. Electronic address:

Domestic waste and municipal sludge are two major solid hazardous substances generated from human daily life. Co-incineration technology is regarded as an effective method for the treatment of them. However, the emitted NO-containing exhaust with high content of phosphorus should purified strictly. CeO-TiO is a promising catalyst for removal of NO by NH-SCR technology, but the effect of phosphorous in the exhaust is ambiguous. Therefore, the effect of phosphorus on NH-SCR performance and physicochemical properties of CeO-TiO catalyst was investigated in our present work. It was found that phosphorus decreased the NH-SCR activity below 300 °C. Interestingly, it suppressed the formation of NO and NO caused by NH over-oxidation above 300 °C. The reason might be that phosphorus induced Ti to migrate from CeO-TiO solid solution and form crystalline TiO, which led to the destruction of Ti-O-Ce structure in the catalyst. So, the transfer of electrons between Ti and Ce ions, the relative contents of Ce, and surface adsorbed oxygen, as well as the redox performance were limited, which further inhibited the over-oxidation of NH. In addition, phosphorus weakened the NH adsorption on Lewis acid sites and the adsorption performance of NO + O, while increased the Brønsted acid sites. Finally, the reaction mechanism over CeO-TiO catalyst did not change after introducing phosphorus, L-H and E-R mechanisms co-existed on the surface of the catalysts.
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http://dx.doi.org/10.1016/j.jcis.2021.11.013DOI Listing
November 2021

An E2F5-TFDP1-BRG1 Complex Mediates Transcriptional Activation of MYCN in Hepatocytes.

Front Cell Dev Biol 2021 22;9:742319. Epub 2021 Oct 22.

Department of Hepatobiliary Surgery, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Liver regeneration is characterized by cell cycle reentrance of hepatocytes. N-Myc, encoded by MYCN, is a member of the Myc family of transcription factors. Elevation of MYCN expression has been noted in the course of liver regeneration whereas the underlying mechanism remains unclear. Here we describe that up-regulation of MYCN expression, as measured by quantitative PCR, Western blotting, and immunohistochemical staining, paralleled liver regeneration in animal and cell models. MYCN expression was up-regulated as a result of transcriptional activation. Ingenuity pathway analysis (IPA) revealed several up-stream transcriptional regulators for MYCN and RNA interference validated E2F5 and TFDP1 as essential for hepatocyte growth factor (HGF)-induced MYCN -activation. Further examination showed that deficiency of BRG1, a chromatin remodeling protein, attenuated MYCN induction during liver regeneration. BRG1 interacted with and was recruited by E2F5/TFDP1 to the MYCN promoter. Mechanistically, BRG1 might play a role regulating histone H3 acetylation and H3K4 trimethylation and facilitating/stabilizing the binding of RNA polymerase II surrounding the MYCN promoter. Over-expression of ectopic MYCN in BRG1-null hepatocytes overcame deficiency of proliferation. Importantly, a positive correlation between MYCN expression and BRG1/E2F5/TFDP1 expression was observed in human liver specimens. In conclusion, our data identify a novel epigenetic pathway where an E2F5-TFDP1-BRG1 complex regulates MYCN transcription to promote liver regeneration.
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http://dx.doi.org/10.3389/fcell.2021.742319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569672PMC
October 2021

Development of a prognostic signature of patients with esophagus adenocarcinoma by using immune-related genes.

BMC Bioinformatics 2021 Nov 1;22(1):536. Epub 2021 Nov 1.

Department of Thoracic Surgery, Jining First People's Hospital, Jining, Shandong, China.

Background: Esophageal adenocarcinoma (EAC) is an aggressive malignancy with a poor prognosis. The immune-related genes (IRGs) are crucial to immunocytes tumor infiltration. This study aimed to construct a IRG-related prediction signature in EAC.

Methods: The related data of EAC patients and IRGs were obtained from the TCGA and ImmPort database, respectively. The cox regression analysis constructed the prediction signature and explored the transcription factors regulatory network through the Cistrome database. TIMER database and CIBERSORT analytical tool were utilized to explore the immunocytes infiltration analysis.

Results: The prediction signature with 12 IRGs (ADRM1, CXCL1, SEMG1, CCL26, CCL24, AREG, IL23A, UCN2, FGFR4, IL17RB, TNFRSF11A, and TNFRSF21) was constructed. Overall survival (OS) curves indicate that the survival rate of the high-risk group is significantly shorter than the low-risk group (P = 7.26e-07), and the AUC of 1-, 3- and 5- year survival prediction rates is 0.871, 0.924, and 0.961, respectively. Compared with traditional features, the ROC curve of the risk score in the EAC patients (0.967) is significant than T (0.57), N (0.738), M (0.568), and Stage (0.768). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are accurate by the combined analysis of the risk score, Sex, M stage, and Stage (The AUC of 1- and 3-years are 0.911, and 0.853).

Conclusion: The 12 prognosis-related IRGs might be promising therapeutic targets for EAC.
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http://dx.doi.org/10.1186/s12859-021-04456-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559413PMC
November 2021

Acute-On-Chronic Liver Failure Defined by Asian Pacific Association for the Study of the Liver Should Include Decompensated Cirrhosis.

Front Med (Lausanne) 2021 15;8:750061. Epub 2021 Oct 15.

Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China.

Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver disease with high short-term mortality. The inclusion or exclusion of previously decompensated cirrhosis (DC) in the diagnostic criteria of ACLF defined by the Asian Pacific Association for the Study of the Liver (APASL-ACLF) has not been conclusive. We aimed to evaluate the prognostic impact of decompensated cirrhosis in ACLF. We retrospectively collected a cohort of patients with a diagnosis of APASL-ACLF (with or without DC) hospitalized from 2012 to 2020 at three liver units in tertiary hospitals. Baseline characteristics and survival data at 28, 90, 180, 360, 540, and 720 days were collected. Of the patients assessed using APASL-ACLF criteria without the diagnostic indicator of chronic liver disease, 689 patients were diagnosed with ACLF, of whom 435 had no decompensated cirrhosis (non-DC-ACLF) and 254 had previously decompensated cirrhosis (DC-ACLF). The 28-, 90-, 180-, 360-, 540-, and 720-day mortality were 24.8, 42.9, 48.7, 57.3, 63.4, and 68.1%, respectively, in DC-ACLF patients, which were significantly higher than in non-DC-ACLF patients ( < 0.05). DC was independently associated with long-term (180/360/540/720 days) but not short-term (28/90 days) mortality in patients with ACLF. Age, total bilirubin, international normalized ratio, and hepatic encephalopathy were independent risk factors for short- and long-term mortality risk in ACLF patients ( < 0.05). Patients with DC-ACLF have a higher mortality rate, especially long-term mortality, compared to non-DC-ACLF patients. Therefore, DC should be included in the diagnostic criteria of APASL-ACLF and treated according to the ACLF management process.
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http://dx.doi.org/10.3389/fmed.2021.750061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554226PMC
October 2021

Clinical Course and Outcome Patterns of Acute-on-chronic Liver Failure: A Multicenter Retrospective Cohort Study.

J Clin Transl Hepatol 2021 Oct 16;9(5):626-634. Epub 2021 Apr 16.

Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China.

Background And Aims: Acute-on-chronic liver failure (ACLF) is acute decompensation of liver function in the setting of chronic liver disease, and characterized by high short-term mortality. In this study, we sought to investigate the clinical course of patients at specific time points, and to propose dynamic prognostic criteria.

Methods: We assessed the clinical course of 453 patients with ACLF during a 12-week follow-up period in this retrospective multicenter study. The clinical course of patients was defined as disease recovery, improvement, worsening or steady patterns based on the variation tendency in prothrombin activity (PTA) and total bilirubin (TB) at different time points.

Results: Resolution of PTA was observed in 231 patients (51%) at 12 weeks after the diagnosis of ACLF. Among the remaining patients, 66 (14.6%) showed improvement and 156 (34.4%) showed a steady or worsening course. In patients with resolved PTA, the clinical course of TB exhibited resolved pattern in 95.2%, improved in 3.9%, and steady or worse in 0.8%. Correspondingly, in patients with improved PTA, these values for TB were 28.8%, 27.3%, and 43.9%, respectively. In patients with steady or worsening PTA, these values for TB were 5.7%, 32.3%, and 65.6%, respectively. Dynamic prognostic criteria were developed by combining the clinical course of PTA/TB and the clinical outcomes at 4 and 12 weeks after diagnosis in ACLF patients.

Conclusions: We propose the following dynamic prognostic criteria: rapid progression, slow progression, rapid recovery, slow recovery, and slow persistence, which lay the foundation for precise prediction of prognosis and the improvement of ACLF therapy.
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http://dx.doi.org/10.14218/JCTH.2020.00179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516834PMC
October 2021

Down-Regulation of CXXC5 De-Represses MYCL1 to Promote Hepatic Stellate Cell Activation.

Front Cell Dev Biol 2021 21;9:680344. Epub 2021 Sep 21.

Department of Hepatobiliary Surgery, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Liver fibrosis is mediated by myofibroblasts, a specialized cell type involved in wound healing and extracellular matrix production. Hepatic stellate cells (HSC) are the major source of myofibroblasts in the fibrotic livers. In the present study we investigated the involvement of CXXC-type zinc-finger protein 5 (CXXC5) in HSC activation and the underlying mechanism. Down-regulation of CXXC5 was observed in activated HSCs compared to quiescent HSCs both and . In accordance, over-expression of CXXC5 suppressed HSC activation. RNA-seq analysis revealed that CXXC5 influenced multiple signaling pathways to regulate HSC activation. The proto-oncogene MYCL1 was identified as a novel target for CXXC5. CXXC5 bound to the proximal MYCL1 promoter to repress MYCL1 transcription in quiescent HSCs. Loss of CXXC5 expression during HSC activation led to the removal of CpG methylation and acquisition of acetylated histone H3K9/H3K27 on the MYCL1 promoter resulting in MYCL1 trans-activation. Finally, MYCL1 knockdown attenuated HSC activation whereas MYCL1 over-expression partially relieved the blockade of HSC activation by CXXC5. In conclusion, our data unveil a novel transcriptional mechanism contributing to HSC activation and liver fibrosis.
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http://dx.doi.org/10.3389/fcell.2021.680344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490686PMC
September 2021

Enhancement of efficiency on the Pancharatnam-Berry geometric phase metalens in the terahertz region.

Appl Opt 2021 Sep;60(26):7849-7857

Traditional terahertz lenses face high thickness, low transmittance, difficult processing, and other problems that are not conducive to mass production and integration. Here, we propose a wideband all-dielectric Pancharatnam-Berry geometric phase cell structure to construct a metasurface flat lens. However, when the geometrical phase element structure rotates, the transmission efficiency of the periodic element structure obviously decreases, which will lead to the decrease of the efficiency of the designed flat lens. In order to improve the efficiency, we propose to add a layer of tapered microstructure on the flat substrate to greatly improve the transmission efficiency of the element structure, thus leading to the improvement of the efficiency of the metasurface lens. By comparing the metasurface lens with conical and planar substrates, the metasurfaces with conical structure can greatly improve the transmission efficiency at broadband and wide angle ranges.
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http://dx.doi.org/10.1364/AO.433115DOI Listing
September 2021

Systematic comparisons of dissolving and swelling hyaluronic acid microneedles in transdermal drug delivery.

Int J Biol Macromol 2021 Nov 28;191:783-791. Epub 2021 Sep 28.

College of Marine Life Science, Ocean University of China, 5 Yushan Road, 266003 Qingdao, China. Electronic address:

Transdermal drug delivery efficacy of hyaluronic acid dissolving microneedles (HA DMNs) is limited by low loading dose and poor drug condensation in needles. HA swelling MNs (HA SMNs) could improve the efficacy, but comparisons between the formulations is missing. In this work, DMNs and SMNs were fabricated of HA and methacrylated HA, respectively. Their properties of transdermal drug delivery were systematically compared. HA SMNs exhibited enhanced mechanical strength, fast swelling performance, and extended duration of microchannels in skin. The doxorubicin (DOX) loaded by one-step loading protocol in needles and baseplate of SMNs could be transdermally delivered through the diffusing path mediated by swollen needles, conquering the limit of poor drug condensation in DMNs needles and generated a longer Tmax but higher Cmax. The relative bioavailability of DOX/SMNs towards DOX/DMNs was 200% within 12 h. The results provide theoretical references for the application of HA MNs mediated transdermal drug delivery.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.161DOI Listing
November 2021

Error Analysis of the Combined-Scan High-Speed Atomic Force Microscopy.

Sensors (Basel) 2021 Sep 13;21(18). Epub 2021 Sep 13.

College of Metrology and Measurement Engineering, China Jiliang University, Hangzhou 310018, China.

A combined tip-sample scanning architecture can improve the imaging speed of atomic force microscopy (AFM). However, the nonorthogonality between the three scanners and the nonideal response of each scanner cause measurement errors. In this article, the authors systematically analyze the influence of the installation and response errors of the combined scanning architecture. The experimental results show that when the probe in the homemade high-speed AFM moves with the Z-scanner, the spot position on the four-quadrant detector changes, thus introducing measurement error. Comparing the experimental results with the numerical and theoretical results shows that the undesired motion of the Z-scanner introduces a large error. The authors believe that this significant error occurs because the piezoelectric actuator not only stretches along the polarization direction but also swings under nonuniform multifield coupling. This article proposes a direction for further optimizing the instrument and provides design ideas for similar high-speed atomic force microscopes.
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http://dx.doi.org/10.3390/s21186139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471258PMC
September 2021

Redox-sensitive activation of CCL7 by BRG1 in hepatocytes during liver injury.

Redox Biol 2021 10 24;46:102079. Epub 2021 Jul 24.

Key Laboratory of Targeted Invention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, China; College of Life Sciences and Institute of Biomedical Research, Liaocheng University, China. Electronic address:

Liver injuries induced by various stimuli share in common an acute inflammatory response, in which circulating macrophages home to the liver parenchyma to participate in the regulation of repair, regeneration, and fibrosis. In the present study we investigated the role of hepatocyte-derived C-C motif ligand 7 (CCL7) in macrophage migration during liver injury focusing on its transcriptional regulation. We report that CCL7 expression was up-regulated in the liver by lipopolysaccharide (LPS) injection (acute liver injury) or methionine-and-choline-deficient (MCD) diet feeding (chronic liver injury) paralleling increased macrophage infiltration. CCL7 expression was also inducible in hepatocytes, but not in hepatic stellate cells or in Kupffer cells, by LPS treatment or exposure to palmitate in vitro. Hepatocyte-specific deletion of Brahma-related gene 1 (BRG1), a chromatin remodeling protein, resulted in a concomitant loss of CCL7 induction and macrophage infiltration in the murine livers. Of interest, BRG1-induced CCL7 transcription and macrophage migration was completely blocked by the antioxidant N-acetylcystine. Further analyses revealed that BRG1 interacted with activator protein 1 (AP-1) to regulate CCL7 transcription in hepatocytes in a redox-sensitive manner mediated in part by casein kinase 2 (CK2)-catalyzed phosphorylation of BRG1. Importantly, a positive correlation between BRG1/CCL7 expression and macrophage infiltration was identified in human liver biopsy specimens. In conclusion, our data unveil a novel role for BRG1 as a redox-sensitive activator of CCL7 transcription.
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http://dx.doi.org/10.1016/j.redox.2021.102079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406035PMC
October 2021

Interactions of heavy metal elements across sediment-water interface in Lake Jiaogang.

Environ Pollut 2021 Oct 12;286:117578. Epub 2021 Jun 12.

Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing, 210042, China.

Heavy metal pollution in lake systems has arisen plenty of threats for public health because of its high toxicity, persistence, and bioaccumulation. Whereas heavy metals are inextricably linked with bioavailability in pore water and overlying water. Lake Jiaogang is classified as an important water-carrying lake situated in the northern part of the Anhui Province China. In recent years, water quality in this lake declined due to increasing fishery aquaculture, livestock, and tourism. This study aims to bring insight into the interactions of heavy metal elements across sediment-water interface in Lake Jiaogang. Four representative regions were selected, more than ten heavy metals were chosen to quantify by the Community Bureau of Reference, diffusive gradient in thin-film (DGT), and high-resolution pore water equilibrators. The results showed that most heavy metals corresponded with the reducible fraction, acid-soluble fraction, and oxidizable fraction in the Eastern area (sample 3) and aquaculture area (sample 4) were higher than that of emergent plant area (sample 1), and floating plant area (sample 2). The average fluxes of heavy metals (except Ni and Zn in sample 3, F value > 0 pg/cm/d) in the four sampling sites were observed in the lower reaches (F value < 0 pg/cm/d). The vertical distribution of heavy metals was extracted by DGT, such as As (exclude 2), Co, Fe, Mn, and Zn (contain 4) showed an increased content with increasing depth in the four sampling sites. In the pore and overlying water, concentrations of heavy metals from the sample 3 and 4 were higher than those of sample 1 and 2. Heavy metal pollution in anthropogenic activity areas was higher than those in areas with ecological vegetation, and risk control in this area should be strengthened.
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http://dx.doi.org/10.1016/j.envpol.2021.117578DOI Listing
October 2021

Efficacy and safety of transcatheter arterial chemoembolization combined with ginsenosides in hepatocellular carcinoma treatment.

Phytomedicine 2021 Oct 8;91:153700. Epub 2021 Aug 8.

Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China. Electronic address:

Background: Transcatheter arterial chemoembolization (TACE) is a standard therapy to treat hepatocellular carcinoma (HCC), but often limited for its complications. Ginsenosides, including total ginsenosides (GS), Rg3, Rh2 and CK, have been clinically used as adjuvants of TACE in HCC therapy. However, partial clinical observations concerning the efficacy and safety of the combinational treatment were contradictory.

Purpose: To investigate the efficacy and safety of TACE and ginsenosides combination for HCC therapy.

Methods: Randomized controlled trials (RCTs) regarding TACE and ginsenosides for HCC up to May 2021 were screened from six databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information and Web of Science). The outcomes of tumor response, adverse reactions (ADRs), quality of life (QOL), survival rates (OS) and liver function were extracted and evaluated by meta-analysis, respectively.

Results: A total of 18 RCTs with 1308 HCC patients were enrolled, and most of the eligible studies had unclear bias risk. Compared with TACE, combining ginsenosides improved objective response rate [ORR, risk ratio (RR) 1.39, 95% confidence intervals (CI) 1.20∼1.61], disease control rate (DCR, RR 1.21, 95% CI 1.12∼1.30), QOL (RR 1.54, 95% CI 1.25∼1.90), one- (RR 1.37, 95% CI 1.16∼1.62) and two- (RR 1.43, 95% CI 1.06∼1.95) year OS, and A level of Child-pugh, as well as reduced the risks of nausea and vomiting, pyrexia, ache, hyperbilirubinemia, anorexia, fatigue, leukopenia, thrombocytopenia and myelosuppression. Subgroup analyses showed that both short- and long- treatment durations of ginsenosides enhanced the A level of Child-pugh, and reduced nausea and vomiting, ache and hyperbilirubinemia. Besides, combining Rg3 benefited DCR, ORR and QOL, and alleviated nausea and vomiting, hyperbilirubinemia, leukopenia, myelosuppression, thrombocytopenia and α-fetoprotein, while combining GS alleviated nausea and vomiting, ache and hyperbilirubinemia, combining Rh2 alleviated thrombocytopenia, and combining CK alleviated nausea and vomiting, pyrexia, ache and leukopenia, respectively.

Conclusion: The results suggested that combining ginsenosides could continuously benefit the efficacy and safety of TACE in HCC treatment, and Rg3 is the prior selection during the combination.
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http://dx.doi.org/10.1016/j.phymed.2021.153700DOI Listing
October 2021

Choline Kinase Alpha Is a Novel Transcriptional Target of the Brg1 in Hepatocyte: Implication in Liver Regeneration.

Front Cell Dev Biol 2021 6;9:705302. Epub 2021 Aug 6.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Department of Pathophysiology, Collaborative Innovation Center for Cardiovascular Translational Medicine, Nanjing Medical University, Nanjing, China.

Liver regeneration is a key compensatory process in response to liver injury serving to contain damages and to rescue liver functions. Hepatocytes, having temporarily exited the cell cycle after embryogenesis, resume proliferation to regenerate the injured liver parenchyma. In the present study we investigated the transcriptional regulation of choline kinase alpha (Chka) in hepatocytes in the context of liver regeneration. We report that Chka expression was significantly up-regulated in the regenerating livers in the partial hepatectomy (PHx) model and the acetaminophen (APAP) injection model. In addition, treatment with hepatocyte growth factor (HGF), a strong pro-proliferative cue, stimulated Chka expression in primary hepatocytes. Chka depletion attenuated HGF-induced proliferation of hepatocytes as evidenced by quantitative PCR and Western blotting measurements of pro-proliferative genes as well as EdU incorporation into replicating DNA. Of interest, deletion of Brahma-related gene 1 (Brg1), a chromatin remodeling protein, attenuated Chka induction in the regenerating livers in mice and in cultured hepatocytes. Further analysis revealed that Brg1 interacted with hypoxia-inducible factor 1 alpha (HIF-1α) to directly bind to the Chka promoter and activate Chka transcription. Finally, examination of human acute liver failure (ALF) specimens identified a positive correlation between Chka expression and Brg1 expression. In conclusion, our data suggest that Brg1-dependent trans-activation of Chka expression may contribute to liver regeneration.
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http://dx.doi.org/10.3389/fcell.2021.705302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377418PMC
August 2021

Reversible Switching of Single-Molecule Magnetic Behaviour by Desorption/Adsorption of Solvent Ligand in a New Dy(III)-Based Metal Organic Framework.

Front Chem 2021 5;9:714851. Epub 2021 Aug 5.

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.

Two metal-organic frameworks (MOFs), [Dy(BDC)(NO)(DMF)] (, HBDC = terephthalic acid) and [Dy(BDC)(NO)] (), were synthesized. The structures of MOFs and are easy to be reversibly transformed into each other by the desorption or adsorption of coordination solvent molecules. Accordingly, their magnetic properties can also be changed reversibly, which realizes our goals of manipulating on/off single-molecule magnet behaviour. MOF behaves as a single-molecule magnet either with or without DC field. Contrarily, no slow magnetic relaxation was observed in both under zero field and applied field.
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http://dx.doi.org/10.3389/fchem.2021.714851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374150PMC
August 2021

Assessment of Acute Pancreatitis Severity and Prognosis with CT-Measured Body Composition.

Int J Gen Med 2021 27;14:3971-3980. Epub 2021 Jul 27.

Department of Gastroenterology and Hepatology, The PLA Rocket Force Characteristic Medical Center, Beijing, People's Republic of China.

Objective: The aim of this study was to investigate the possible association of muscle and adipose parameters with the severity and prognosis of patients hospitalized with acute pancreatitis (AP).

Methods: A total of 392 hospitalized patients and 309 controls were enrolled in the study analysis from April 1, 2016, to February 1, 2021. The computed tomography scans of each population were evaluated for muscle and adipose parameters. The effects of parameters on developing moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP) were evaluated using univariate and multivariate logistic regression analyses. Associations with disease recurrence and death were analyzed through Cox regression analysis.

Results: The AP patients had higher levels of visceral adipose tissue (144.25 vs 97.81 cm, p < 0.001) and subcutaneous adipose tissue (135 vs 120 cm, p < 0.001) but lower levels of adipose tissue attenuation (visceral and subcutaneous) and skeletal muscle attenuation (SMA) than the controls (p < 0.05, respectively). Visceral adipose tissue (VAT) and SMA differed significantly with p-values of 0.014 and 0.003 in the different severity groups of AP. In multivariate analysis, VAT and SMA were associated with MSAP or SAP, with odds ratios of 1.003 and 0.973, respectively (95% CI 1.000-1.006, p = 0.041; 95% CI 0.953-0.993, p = 0.010). Cox regression analysis showed that low SMA was strongly associated with an increased mortality in MSAP and SAP patients (HR 10.500, 95% CI 1.344-82.025, p = 0.025). Regression analysis also showed an association of VAT loss of more than 17% with reduced 1-year recurrence of acute pancreatitis (HR 0.427, 95% CI 0.189-0.967, p = 0.041).

Conclusion: VAT and SMA were influential factors for the severity and prognosis of patients with AP. Patients should proper diet and exercise after discharge to reduce VAT and strengthen muscle function to improve prognosis.
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http://dx.doi.org/10.2147/IJGM.S322589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326933PMC
July 2021

Use of skeletal muscle index as a predictor of short-term mortality in patients with acute-on-chronic liver failure.

Sci Rep 2021 06 15;11(1):12593. Epub 2021 Jun 15.

Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, 100069, China.

Sarcopenia is a well-recognized factor affecting the prognosis of chronic liver disease, but its impact on acute decompensation underlying chronic liver disease is unknown. This study evaluated the impact of sarcopenia on short-term mortality in patients with acute-on-chronic liver failure (ACLF). One hundred and seventy-one ACLF patients who underwent abdominal CT between 2015 and 2019 were retrospectively included in this study. Skeletal muscle index at the third lumbar vertebrae (L3-SMI) was used to diagnose sarcopenia.The ACLF patients in this study had a L3-SMI of 41.2 ± 8.3 cm/m and sarcopenia was present in 95/171 (55.6%) patients. Body mass index (BMI), cirrhosis, and higher serum bilirubin were independently associated with sarcopenia. Following multivariate Cox regression analysis, cirrhosis (hazard ratio (HR) 2.758, 95%CI 1.323-5.750), serum bilirubin (HR 1.049, 95%CI 1.026-1.073), and international normalized ratio (INR) (HR 1.725, 95%CI 1.263-2.355) were associated with 3-month mortality (P < 0.05), whereas L3-SMI and sarcopenia were not. A subgroup analysis of the factors related to sarcopenia showed that sarcopenia was still not predictive of short-term outcome in ACLF patients. L3-SMI and sarcopenia are not associated with short-term mortality in patients with ACLF.
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http://dx.doi.org/10.1038/s41598-021-92087-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206330PMC
June 2021

Integrating multiple-chromatographic approaches to evaluate chemical consistency of Chang-Kang-Fang preparations from mixed-herb decoction and combined single-herb decoction.

J Pharm Biomed Anal 2021 Sep 3;203:114186. Epub 2021 Jun 3.

Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China. Electronic address:

Chang-Kang-Fang formula (CKF), a multi-herbs traditional Chinese medicine (TCM) prescription for treating irritable bowel syndrome (IBS), has been clinically applied in the traditional form of mixed-herb decoction (MHD), or in the modern form of combined single-herb decoction (cSHD, so called dispensing granule decoction) in the near decades, but the chemical consistency between the MHD and cSHD is still unknown. Herein, a new strategy by integrating multiple-chromatographic approaches to characterize both polysaccharides and small molecules was developed to compare the chemical consistency between MHD and cSHD. Sixteen small molecules were simultaneously qualified and quantified by UPLC-QTOF-MS/MS, the molecular weight distribution of polysaccharides was characterized by HPGPC-ELSD, while the monosaccharide composition and total saccharides content were determined by HPLC-PDA and UV-VIS, respectively. It was found that the molecular weight range and monosaccharide composition of polysaccharides, as well as the composition of small molecules, were identical between MHD and cSHD. However, the contents of berberine, epiberberine, coptisine, palmatine, albiflorin and paeoniflorin in MHD were significantly lower than those in cSHD, whereas the content of polysaccharides in MHD was higher than that in cSHD, indicating that there is a significant difference in the quality between MHD and cSHD, in particular for the relative contents of major small molecules and polysaccharides. Whether or not these quality variations affect the efficacy and safety of CKF deserves further investigation.
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http://dx.doi.org/10.1016/j.jpba.2021.114186DOI Listing
September 2021

Rapid differential detection of subtype H1 and H3 swine influenza viruses using a TaqMan-MGB-based duplex one-step real-time RT-PCR assay.

Arch Virol 2021 Aug 6;166(8):2217-2224. Epub 2021 Jun 6.

Animal Infectious Diseases Laboratory, College of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu, China.

Swine influenza is an economically important respiratory disease in swine, but it also constantly poses a threat to human health. Therefore, developing rapid, sensitive, and efficient detection methods for swine influenza virus (SIV) is important. By aligning the haemagglutinin (HA) gene sequences of SIVs circulating in China over a 10-year period, an H1 primer-probe set targeting both Eurasian avian-like H1N1 (EA H1N1) and pandemic 2009 H1N1 ((H1N1)pdm09) lineages plus a H3 primer-probe set targeting the prevalent human-like H3N2 (HL H3N2) subtype were designed. Subsequently, a TaqMan-MGB-based duplex one-step real-time RT-PCR (RT-qPCR) assay was established and evaluated. The duplex RT-qPCR has a detection limit of 5 copies/μL of HA plasmid for EA H1N1, (H1N1)pdm09, and HL H3N2 subtype SIVs, and its overall detection sensitivity of 100% and specificity of 91.67% matches that of traditional virus isolation through chicken embryo inoculation using experimentally infected mouse lung samples. The method showed high repeatability both within run and between runs, and there was no cross-reactivity against several other porcine viruses that are commonly circulating in China. Furthermore, the duplex RT-qPCR method revealed a higher prevalence of subtype H1 than subtype H3 in 166 nasal swabs from pigs collected from one slaughterhouse between October and December 2019. This assay could be very helpful in the rapid differential detection and routine surveillance of EA H1N1, (H1N1)pdm09, and HL H3N2 SIVs in China.
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http://dx.doi.org/10.1007/s00705-021-05127-6DOI Listing
August 2021

Frequency modulation nonlinear correction and range-extension method based on laser frequency scanning interference.

Appl Opt 2021 Apr;60(12):3446-3451

A phase spread frequency sampling method is proposed. This method can be used to correct the nonlinearity in the beat frequency of a measurement signal. The proposed method expands the phase of the auxiliary interference beat signal, thereby satisfying the Nyquist sampling theorem, correcting the nonlinearity in the beat frequency of the measured signal, and solving the problem of limited range. The conditions over which the frequency sampling method can be applied are expanded. The measurement range is flexibly expanded by performing multiple phase expansions.
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http://dx.doi.org/10.1364/AO.420663DOI Listing
April 2021

Ginseng ameliorates exercise-induced fatigue potentially by regulating the gut microbiota.

Food Funct 2021 May;12(9):3954-3964

Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, Jiangsu, People's Republic of China. and Department of Pharmaceutical Analysis, Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.

The therapeutic effects of water extract of ginseng (WEG) on exercise-induced fatigue (EF) have been reported in several previous studies, but the molecular mechanisms involved remain unexplored. In this study, the anti-EF effects of WEG were studied, and the potential mechanisms were discussed. We characterized the chemical components of WEG by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD), and then examined the anti-EF effects of WEG on a rat model of weight-loaded swimming with a focus on endogenous metabolism and gut microbiota. WEG contains abundant (90.15%, w/w) saccharides and ginsenosides with structurally diverse glycosyls. WEG taken orally showed strong anti-EF effects by ameliorating energy metabolism abnormality, oxidative stress, lipid peroxidation, inflammatory response, disorders in the metabolism of bile acid, amino acid, fatty acid and lipid, as well as the gut microbiota dysbiosis. Given that gut microbiota is significantly associated with energy expenditure, systemic inflammation and host metabolism, these findings suggest a potential central role of the gut microbiota in mediating the anti-EF effect of WEG. That is, the saccharides and ginsenosides in WEG serve as energy substrates for specific intestinal bacteria, thereby beneficially regulating the gut microbiota, and the reshaped gut microbial ecosystem then triggers several molecular and cellular signaling pathways (e.g. butyrate or TGR5 signals) to achieve the therapeutic effects on EF. The outcomes highlighted here enable deeper insight into how WEG overcomes EF.
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http://dx.doi.org/10.1039/d0fo03384gDOI Listing
May 2021

High-accuracy deflectometric microscope system with a large slope range.

Opt Lett 2021 May;46(9):2011-2014

We propose an off-axis deflectometric microscope system for microscopic surface testing with both high measurement accuracy and a large slope dynamic range. A high-luminance liquid crystal display directly illuminates the tested sample with coded fringes, and then the reflected fringes passing through a microscope objective are captured by a pinhole camera, from which the deflectometric microscopic testing with a large slope range can be achieved. The accuracy of the proposed system is validated numerically and experimentally, and a large measurable slope dynamic range is also demonstrated. The proposed system provides a feasible way with the slope range in the order of sub-radians and sag resolution better than 0.05 nm.
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http://dx.doi.org/10.1364/OL.420447DOI Listing
May 2021

Dual cure (thermal/photo) composite hydrogel derived from chitosan/collagen for in situ 3D bioprinting.

Int J Biol Macromol 2021 Jul 16;182:689-700. Epub 2021 Apr 16.

College of Marine Life Science, Ocean University of China, 5 Yushan Road, 266003 Qingdao, China. Electronic address:

In situ 3D printing technologies is a new frontier for highly personalized medicine, which requires suitable bioink with rheology, biocompatibility, and gelation kinetics to support the right shape and mechanical properties of the printed construct. To this end, a facile design of thermo/photo dual cure composite hydrogel was proposed using MHBC and soluble collagen in this study. M/C composite hydrogel exhibited rapid thermo-induced sol-gel transition and contraction, tunable mechanical properties, proper microstructure and biodegradability for 3D cell culture, as well as improve cyto-compatibility, all of which were dependent upon the methacrylation degree of MHBC and M/C ratios. The printability of the optimal formulation (3% MHBC/1% collagen) was validated by its mild printing condition, rapid gelation of bioink at 37 °C and simple postprocessing manipulation. Both desirable printability and cyto-compatibility enable M/C composite hydrogel a potential candidate as bioink to be applied for in situ 3D bioprinting.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.058DOI Listing
July 2021

Myocardin-related transcription factor A (MRTF-A) regulates integrin beta 2 transcription to promote macrophage infiltration and cardiac hypertrophy in mice.

Cardiovasc Res 2021 Mar 22. Epub 2021 Mar 22.

Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.

Aims: Macrophage-mediated inflammatory response represents a key pathophysiological process in a host of cardiovascular diseases including heart failure. Regardless of etiology, heart failure is invariably preceded by cardiac hypertrophy. In the present study we investigated the effect of macrophage-specific deletion of myocardin-related transcription factor A (MRTF-A) on cardiac hypertrophy and the underlying mechanism.

Methods And Results: We report that when subjected to transverse aortic constriction (TAC), macrophage MRTF-A conditional knockout (CKO) mice developed a less severe phenotype of cardiac hypertrophy compared to wild type (WT) littermates and were partially protected from the loss of heart function. In addition, there was less extensive cardiac fibrosis in the CKO mice than WT mice following the TAC procedure. Further analysis revealed that cardiac inflammation, as assessed by levels of pro-inflammatory cytokines and chemokines, was dampened in CKO mice paralleling reduced infiltration of macrophages in the heart. Mechanistically, MRTF-A deficiency attenuated the expression of integrin beta 2 (ITGB2/CD18) in macrophage thereby disrupting adhesion of macrophages to vascular endothelial cells. MRTF-A was recruited by Sp1 to the ITGB2 promoter and cooperated with Sp1 to activate ITGB2 transcription in macrophages. Administration of a CD18 blocking antibody attenuated TAC induced cardiac hypertrophy in mice. Interaction between MRTF-A and the histone demethylase KDM3A likely contributed to IGTB2 transcription and consequently adhesion of macrophages to endothelial cells.

Conclusions: Our data suggest that MRTF-A may regulate macrophage trafficking and contribute to the pathogenesis of cardiac hypertrophy by activating ITGB2 transcription.
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http://dx.doi.org/10.1093/cvr/cvab110DOI Listing
March 2021

The Chromatin Remodeling Protein BRG1 Regulates SREBP Maturation by Activating SCAP Transcription in Hepatocytes.

Front Cell Dev Biol 2021 25;9:622866. Epub 2021 Feb 25.

Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.

Sterol response element binding protein (SREBP) is a master regulator of cellular lipogenesis. One key step in the regulation of SREBP activity is its sequential cleavage and location by several different proteinases including SREBP cleavage activating protein (SCAP). We have previously reported that Brahma related gene 1 (BRG1) directly interacts with SREBP1c and SREBP2 to activate pro-lipogenic transcription in hepatocytes. We report here that BRG1 deficiency resulted in reduced processing and nuclear accumulation of SREBP in the murine livers in two different models of non-alcoholic steatohepatitis (NASH). Exposure of hepatocytes to lipopolysaccharide (LPS) and palmitate (PA) promoted SREBP accumulation in the nucleus whereas BRG1 knockdown or inhibition blocked SREBP maturation. Further analysis revealed that BRG1 played an essential role in the regulation of SCAP expression. Mechanistically, BRG1 interacted with Sp1 and directly bound to the SCAP promoter to activate SCAP transcription. Forced expression of exogenous SCAP partially rescued the deficiency in the expression of SREBP target genes in BRG1-null hepatocytes. In conclusion, our data uncover a novel mechanism by which BRG1 contributes to SREBP-dependent lipid metabolism.
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http://dx.doi.org/10.3389/fcell.2021.622866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947303PMC
February 2021

Calibration of geometrical aberration in transmitted wavefront testing of refractive optics with deflectometry.

Appl Opt 2021 Mar;60(7):1973-1981

Deflectometry, with its noticeable advantages such as simple structure, large dynamic range, and high accuracy comparable to interferometry, has been one of the powerful metrological techniques for optical surfaces in recent years. In the "null" deflectometric transmitted wavefront testing of refractive optics, ray tracing of the test system model is required, in which both the miscalibration of system geometrical parameters and optical tolerances on tested optics could introduce significant geometrical aberrations in the testing results. In this paper, the geometrical aberration introduced by a system modeling error in the transmitted wavefront testing is discussed. Besides, a calibration method based on polynomial optimization of geometrical aberration is presented for the geometrical aberration calibration. Both simulation and experiment have been performed to validate the feasibility of the proposed calibration method. The proposed method can calibrate the optical tolerances on tested optics effectively, and it is feasible even with a large geometric error, providing a viable way to address the uncertainty in system modeling in transmitted wavefront testing of freeform refractive optics with large dynamic range.
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http://dx.doi.org/10.1364/AO.415715DOI Listing
March 2021

The virulence modulator PA-X protein has minor effect on the pathogenicity of the highly pathogenic H7N9 avian influenza virus in mice.

Vet Microbiol 2021 Apr 26;255:109019. Epub 2021 Feb 26.

Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China. Electronic address:

PA-X is a novel discovered accessory protein encoded by the PA mRNA of the influenza A virus. Accumulated studies have demonstrated the crucial role of this protein in regulating the virulence of various subtypes of influenza virus, including H1N1, H5N1, H9N2, H1N2, H3N8 and H3N2 virus. However, the role of PA-X protein in regulating the virulence of the highly pathogenic avian H7N9 virus was unknown. In this study, we firstly generated two recombinant H7N9 viruses which have lower PA-X expression level than the parental H7N9 virus. We then systematically compared their difference in virus replication, polymerase activity, virulence and virus-induced host immune responses in mice. The results showed that the PA-X deficient viruses significantly increased viral replication in madin darby canine kidney cells and slightly increased viral replication in mouse lung. In addition, loss of PA-X expression significantly increased viral polymerase activity and alleviated the host-shutoff activity mediated by the parental PA protein. However, in contrast with the usual function of PA-X in regulating the virulence in different subtype influenza virus, no obvious effect on viral virulence in mice was observed by H7N9 PA-X protein. Furthermore, among the 12 kinds of cytokines and 2 kinds of complement derived components that we tested, the PA-X deficiency viruses only induced significantly higher expression levels of MX1 than the parental virus. Altogether, these results showed that PA-X has little effect on viral virulence and viral induced innate immune response of the H7N9 subtype virus. Our study adds further information for the growing understanding of the complexity of PA-X in regulating viral virulence and host innate immune response of different influenza virus.
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http://dx.doi.org/10.1016/j.vetmic.2021.109019DOI Listing
April 2021

Efficacy of ginseng and its ingredients as adjuvants to chemotherapy in non-small cell lung cancer.

Food Funct 2021 Mar;12(5):2225-2241

Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China. and Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.

Chemotherapy is applied to treat non-small cell lung cancer (NSCLC), but often limited due to its unstable therapeutic effects and adverse reactions (ADRs). Ginseng and its main ingredients (ginsenosides and polysaccharides) have been clinically used as adjuvants to chemotherapy. However, their efficacies were based on individual trials with relatively small sample sizes, and it is difficult to draw a valid conclusion. In this study, eligible randomized controlled trials (RCTs) were searched in six international and Chinese databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information and Wanfang). The outcomes of the objective response rate (ORR), disease control rate (DCR), ADRs, quality of life (QOL), survival rates and immunity were extracted using standard data extraction forms. The efficacies of ginseng and its ingredients as adjuvants to chemotherapy in NSCLC were investigated and compared by meta-analysis and subgroup meta-analysis, respectively. A total of 28 RCTs including 2503 subjects were enrolled, and most of the eligible studies were of low-to-moderate quality. For the evaluation of ginseng and its ingredients as adjuvants to chemotherapy, the risk ratio (RR) or standardized mean difference (SMD) and 95% confidence intervals (CI) of the ORR, DCR, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity, nausea and vomiting, diarrhea, CD4+/CD8+ and one- and two-year survival rates, and QOL were 1.35 (1.21,1.50), 1.20 (1.14,1.28), 0.59 (0.50, 0.70), 0.53 (0.37, 0.76), 0.30 (0.17, 0.53), 0.67 (0.52, 0.87), 0.67 (0.53, 0.86), 0.42 (0.19, 0.96), 1.39 (0.63, 2.16), 1.35 (1.13, 1.60), 3.21 (1.51, 6.81) and 1.31 (1.22, 1.41) with significant differences. Subgroup analysis showed that ginseng enhanced nausea and vomiting and QOL, ginsenosides increased ORR, DCR, QOL, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity, diarrhea, CD4+/CD8+, and one- and two-year survival rates, while polysaccharides improved ORR, DCR, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity and nausea and vomiting during chemotherapy. In conclusion, ginseng and its ingredients facilitated the therapeutic effects of chemotherapy on NSCLC patients. Ginseng had beneficial effects on alleviating ADRs and enhancing QOL, ginsenosides demonstrated beneficial effects on enhancing therapeutic effects, reducing ADRs, improving immunity, prolonging survival rates and promoting QOL, while polysaccharides showed beneficial effects on promoting therapeutic effects and reducing ADRs.
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http://dx.doi.org/10.1039/d0fo03341cDOI Listing
March 2021

BRG1 Mediates Nephronectin Activation in Hepatocytes to Promote T Lymphocyte Infiltration in ConA-Induced Hepatitis.

Front Cell Dev Biol 2020 21;8:587502. Epub 2021 Jan 21.

Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, Nanjing Medicine, Nanjing, China.

Fulminant hepatitis (FH) is a major cause of acute liver failure. Concanavalin A (ConA) belongs to the lectin family and is frequently used as an inducer of FH in animal models. ConA induced FH is characterized by massive accumulation of T lymphocytes in the liver. A host of chemoattractive substances are known to promote T cell homing to the liver during acute hepatitis. Here we investigated the involvement of Brahma-related gene 1 (BRG1), a chromatin remodeling protein, in FH. BRG1-flox mice were crossed to Alb-Cre mice to generate hepatocyte conditional BRG1 knockout (LKO) mice. The mice were peritoneally injected with a single dose of ConA to induce FH. BRG1 deficiency mitigated ConA-induced FH in mice. Consistently, there were fewer T lymphocyte infiltrates in the LKO livers compared to the wild type (WT) livers paralleling downregulation of T cell specific cytokines. Further analysis revealed that BRG1 deficiency repressed the expression of several chemokines critical for T cell homing including nephronectin (Npnt). BRG1 knockdown blocked the induction of Npnt in hepatocytes and attenuated T lymphocyte migration , which was reversed by the addition of recombinant nephronectin. Mechanistically, BRG1 interacted with β-catenin to directly bind to the promoter and activate transcription. Importantly, a positive correlation between infiltration of CD3 T lymphocyes and nephronectin expression was detected in human acute hepatitis biopsy specimens. In conclusion, our data identify a novel role for BRG1 as a promoter of T lymphocyte trafficking by activating transcription in hepatocytes. Targeting the BRG1-Npnt axis may yield novel therapeutic solutions for FH.
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http://dx.doi.org/10.3389/fcell.2020.587502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858674PMC
January 2021

A dynamic prediction model for prognosis of acute-on-chronic liver failure based on the trend of clinical indicators.

Sci Rep 2021 01 19;11(1):1810. Epub 2021 Jan 19.

Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, No. 83, Jintang Road, Hedong District, Tianjin, 300170, China.

Acute-on-chronic liver failure (ACLF) is a dynamic syndrome, and sequential assessments can reflect its prognosis more accurately. Our aim was to build and validate a new scoring system to predict short-term prognosis using baseline and dynamic data in ACLF. We conducted a retrospective cohort analysis of patients with ACLF from three different hospitals in China. To construct the model, we analyzed a training set of 541 patients from two hospitals. The model's performance was evaluated in a validation set of 130 patients from another center. In the training set, multivariate Cox regression analysis revealed that age, WGO type, basic etiology, total bilirubin, creatinine, prothrombin activity, and hepatic encephalopathy stage were all independent prognostic factors in ACLF. We designed a dynamic trend score table based on the changing trends of these indicators. Furthermore, a logistic prediction model (DP-ACLF) was constructed by combining the sum of dynamic trend scores and baseline prognostic parameters. All prognostic scores were calculated based on the clinical data of patients at the third day, first week, and second week after admission, respectively, and were correlated with the 90-day prognosis by ROC analysis. Comparative analysis showed that the AUC value for DP-ACLF was higher than for other prognostic scores, including Child-Turcotte-Pugh, MELD, MELD-Na, CLIF-SOFA, CLIF-C ACLF, and COSSH-ACLF. The new scoring model, which combined baseline characteristics and dynamic changes in clinical indicators to predict the course of ACLF, showed a better prognostic ability than current scoring systems. Prospective studies are needed to validate these results.
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http://dx.doi.org/10.1038/s41598-021-81431-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815739PMC
January 2021

M2-like macrophages exert hepatoprotection in acute-on-chronic liver failure through inhibiting necroptosis-S100A9-necroinflammation axis.

Cell Death Dis 2021 01 18;12(1):93. Epub 2021 Jan 18.

Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, the Fourth Department of hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China.

Necroptosis has emerged as a novel and crucial player in acute and chronic liver diseases. Necroptotic cells lead to the release of DAMPs including S100A9, followed by the development of necroinflammation. We previously have documented the beneficial hepatoprotection conferred by M2-like macrophages in acute-on-chronic liver failure (ACLF) in vitro and in vivo, namely, M2-like macrophages protect hepatocytes against apoptosis. Herein, we integrated necroptosis, S100A9, and necroinflammation into this hepatoprotection, and hypothesized M2-like macrophages exert a hepatoprotective effect through inhibiting necroptosis-S100A9-necroinflammation axis. To testify this hypothesis, control mice were pre-treated with necroptosis or S100A9 inhibitors followed by D-GalN/LPS challenge. The extent of liver injury and M1/M2 macrophage activation was assessed. Necroptosis signaling and S100A9 expression were analysed and compared in control and fibrotic mice with or without acute insult. To document the pivotal role of M2-like macrophages in necroptosis and S100A9 inhibition, loss-of-function and gain-of-function experiments were performed. In addition, necroinflammation and its dependence on necroptosis and S100A9 were analysed. Moreover, the inhibitory effects of M2-like macrophages on necroinflammation were investigated in vivo and in vitro. We found that: firstly, the inhibition of necroptosis signaling and S100A9 expression alleviated D-GalN/LPS-induced hepatic damage, which was accompanied by M2-like macrophage activation; secondly, fibrosis inhibited necroptosis signaling and S100A9 expression, which could be attributed to M2-like macrophage activation; thirdly, S100A9 may function as a downstream player of necroptosis signaling; fourthly, fibrosis suppressed necroptosis- and S100A9-dependent necroinflammation; and finally, M2-like macrophages inhibited NLRP3 inflammasome activation and resultant necroinflammation via IL-10. Therefore, M2-like macrophages exert a beneficial hepatoprotection by inhibiting necroptosis-S100A9-necroinflammation axis in ACLF. Our findings provide novel insight for treating ACLF patients by specially targeting this signaling axis.
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http://dx.doi.org/10.1038/s41419-020-03378-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814003PMC
January 2021
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