Publications by authors named "Shinan Nie"

29 Publications

  • Page 1 of 1

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Front Psychiatry 2021 14;12:566990. Epub 2021 Jun 14.

Department of Emergency Medicine, The First Affiliate Hospital of Xinjiang Medical University, Wulumuqi, China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.
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http://dx.doi.org/10.3389/fpsyt.2021.566990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236535PMC
June 2021

Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway.

Front Pharmacol 2021 30;12:627716. Epub 2021 Apr 30.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and LPS-induced RAW264.7 cell ALI model. Mice were pretreated with XBJ before the CLP model was established, and serum and liver tissues were collected at the end of the experiment to assess the levels of inflammatory factors and liver injury. Results showed that XBJ pretreatment reduced liver/body weight, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum, and inhibited levels of pro-inflammatory factors in serum. Cells were treatment with XBJ and modeled by LPS modeling increased cell viability in the XBJ-treated group compared to the model group and XBJ also decreased serum pro-inflammatory factors in a dose-dependent manner. Western blot detected that XBJ also up-regulated the phosphorylated levels of glycogen synthase kinase-3β (p-GSK-3β) and cAMP-response element-binding protein (p-CREB) and down-regulated the phosphorylated level of nuclear factor kappa-B (p-NF-κB) in liver and cell. After overexpression of GSK-3β in cells, the mechanism was further investigated using CO-IP analysis. The binding of p-NF-κB and p-CREB to CREB-binding protein (CBP) was increased and decreased, respectively, indicating that GSK-3β regulated inflammation by regulating the binding of p-NF-κB and p-CREB to CBP. The present studies suggested that the hepatoprotective effect of XBJ may be through up-regulation of GSK-3β (Ser9) and increasing the binding of p-CREB to CBP, thereby alleviating the inflammatory response.
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http://dx.doi.org/10.3389/fphar.2021.627716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120308PMC
April 2021

Ferulic acid positively modulates the inflammatory response to septic liver injury through the GSK-3β/NF-κB/CREB pathway.

Life Sci 2021 Jul 4;277:119584. Epub 2021 May 4.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address:

Aims: Ferulic acid (FA) is a component found in plants that has free radical scavenging and liver-protective properties. Acute liver injury (ALI) is a serious complication of sepsis and is closely associated with changes in the levels of inflammatory factors. This study was taken to examine the role of FA in cecal ligation and perforation (CLP)-induced murine ALI and lipopolysaccharide (LPS)-induced cellular ALI models.

Materials And Methods: An in vivo ALI model was established by performing CLP surgery on C57BL/6 mice. After the ALI model was established, mice were examined for liver injury, including HE staining to observe tissue sections, the percentage of liver/body weight and inflammatory factor levels. Myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured in liver or serum using commercial kits. An in vitro ALI model was established using LPS-stimulated RAW264.7 cells. Cell viability was measured by MTT method and the intracellular levels of IL-10, IL-1β, IL-6, IL-12 and TNF-α inflammatory factors were measured using kits. The expression of GSK-3β, NF-κB and CREB was measured by western blot or immunofluorescence.

Key Findings: FA pretreatment significantly reduced liver/body weight ratio, decreased MPO, AST and ALT activity, alleviated the inflammatory responses and improved CLP-induced histopathological changes in liver. In addition, in vitro results showed that FA could dose-dependently increase the viability of RAW264.7 cells and decrease the levels of pro-inflammatory factors.

Significance: In conclusion, our data suggest that FA can ameliorate ALI-induced inflammation via the GSK-3β/NF-κB/CREB pathway, suggesting that FA can be used to protect the liver against ALI.
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http://dx.doi.org/10.1016/j.lfs.2021.119584DOI Listing
July 2021

Arctigenin Suppressed Epithelial-Mesenchymal Transition Through Wnt3a/β-Catenin Pathway in PQ-Induced Pulmonary Fibrosis.

Front Pharmacol 2020 16;11:584098. Epub 2020 Dec 16.

Department of Emergency Medicine, Jinling Clinical College of Nanjing Medical University, Nanjing, China.

Arctigenin (ATG), a major bioactive substance of Fructus Arctii, counters renal fibrosis; however, whether it protects against paraquat (PQ)-induced lung fibrosis remains unknown. The present study was to determine the effect of ATG on PQ-induced lung fibrosis in a mouse model and the underlying mechanism. Firstly, we found that ATG suppressed PQ-induced pulmonary fibrosis by blocking the epithelial-mesenchymal transition (EMT). ATG reduced the expressions of Vimentin and α-SMA (lung fibrosis markers) induced by PQ and restored the expressions of E-cadherin and Occludin (two epithelial markers) and . Besides, the Wnt3a/β-catenin signaling pathway was significantly activated in PQ induced pulmonary fibrosis. Further analysis showed that pretreatment of ATG profoundly abrogated PQ-induced EMT-like phenotypes and behaviors in A549 cells. The Wnt3a/β-catenin signaling pathway was repressed by ATG treatment. The overexpression of Wnt3a could weaken the therapeutic effect of ATG in A549 cells. These findings suggested that ATG could serve as a new therapeutic candidate to inhibit or even reverse EMT-like changes in alveolar type II cells during PQ-induced lung fibrosis, and unraveled that the Wnt3a/β-catenin pathway might be a mechanistic tool for ATG to control pulmonary fibrosis.
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http://dx.doi.org/10.3389/fphar.2020.584098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772408PMC
December 2020

The influence of coronavirus disease 2019 on emergency department visits in Nanjing, China: A multicentre cross-sectional study.

Am J Emerg Med 2020 Oct 9;38(10):2101-2109. Epub 2020 Aug 9.

Department of Emergency, Nanjing Central Hospital, 116, Chengxian Street, Nanjing, Jiangsu 210018, People's Republic of China.

Introduction: Influenza has been linked to the crowding in emergency departments (ED) across the world. The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on China EDs has been quite different from those during past influenza outbreaks. Our objective was to determine if COVID-19 changed ED visit disease severity during the pandemic.

Methods: This was a retrospective cross sectional study conducted in Nanjing, China. We captured ED visit data from 28 hospitals. We then compared visit numbers from October 2019 to February 2020 for a month-to-month analysis and every February from 2017 to 2020 for a year-to-year analysis. Inter-group chi-square test and time series trend tests were performed to compare visit numbers. The primary outcome was the proportion of severe disease visits in the EDs.

Results: Through February 29 2020, there were 93 laboratory-confirmed COVID-19 patients in Nanjing, of which 40 cases (43.01%) were first seen in the ED. The total number of ED visits in Nanjing in February 2020, were dramatically decreased (n = 99,949) in compared to January 2020 (n = 313,125) and February 2019 (n = 262,503). Except for poisoning, the severe diseases in EDs all decreased in absolute number, but increased in proportion both in year-to-year and month-to-month analyses. This increase in proportional ED disease severity was greater in higher-level referral hospitals when compared year by year.

Conclusion: The COVID-19 outbreak has been associated with decreases in ED visits in Nanjing, China, but increases in the proportion of severe ED visits.
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http://dx.doi.org/10.1016/j.ajem.2020.07.086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415345PMC
October 2020

Long non-coding RNA Hsp4 alleviates lipopolysaccharide-induced apoptosis of lung epithelial cells via miRNA-466m-3p/DNAjb6 axis.

Exp Mol Pathol 2020 12 23;117:104547. Epub 2020 Sep 23.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address:

Acute lung injury (ALI), as a life-threatening syndrome, is mainly characterized with diffuse alveolar injury, excessive pulmonary inflammation, edema and apoptosis of lung epithelial cells. This study investigated the effects of LncRNA Hsp4 (Hsp4, ENSMUST00000175718) on lipopolysaccharide (LPS)-induced apoptosis of MLE-12 cells. In our research, we found that LPS treatment remarkably induced apoptosis of MLE-12 cells and decreased the expression of Hsp4. Overexpression of Hsp4 significantly reversed LPS-induced cell apoptosis through inhibiting mTOR signaling, while suppression of Hsp4 presented opposite effects. Further results showed that Hsp4 positively regulated the expression of miR-466m-3p. Knockdown of miR-466m-3p reversed LPS-induced cell apoptosis via increasing the levels of DNAjb6 which was confirmed to be the target gene of miR-466m-3p. This finding will be helpful for further understanding the critical roles of Hsp4 in ALI and may provide potential targets for ALI diagnosis and treatment.
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http://dx.doi.org/10.1016/j.yexmp.2020.104547DOI Listing
December 2020

Paraquat induces pulmonary fibrosis through Wnt/β-catenin signaling pathway and myofibroblast differentiation.

Toxicol Lett 2020 Oct 11;333:170-183. Epub 2020 Aug 11.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Southern Medical University, Nanjing, 210002, PR China. Electronic address:

Paraquat (PQ) poisoning-induced pulmonary fibrosis always results in fatal harm to patients. Our study aimed to investigate the functions of the Wnt/β-catenin pathway in PQ-induced pulmonary fibrosis. By comparing the proteomic profiles of rat lung tissues using protein array in the absence or presence of PQ, the Wnt/β-catenin signaling, as a fibrosis-related pathway, was discovered to be profoundly activated by PQ. The protein levels of Wnt/β-catenin signaling components including MMP-2, β-catenin, Wnt3a, Wnt10b, Cyclin D1, and WISP1 were increased in PQ-treated rat lung tissues. Surprisingly, PQ was found to be able to promote lung epithelial cells and fibroblasts differentiating into myofibroblasts by activating Wnt/β-catenin signaling pathway. Dickkopf-1 (DKK1), an antagonist of Wnt/β-catenin signaling pathway, could inhibit the myofibroblast differentiation and attenuate PQ-induced pulmonary fibrogenesis in vitro and in vivo. The expression levels of fibroblasts markers Vimentin, α-smooth muscle actin (α-SMA) and Collagen I was detected and found to be increased when PQ treated and restored with additional DKK1 treatment. In summary, these assays indicated that Wnt/β-catenin signaling pathway played a regulatory role in the differentiation of lung epithelial cells and fibroblasts, and the pathogenesis of pulmonary fibrosis related to PQ. Inhibition of the Wnt/β-catenin signaling pathway may be investigated further as a potential fibrosis suppressor for pulmonary fibrosis therapy.
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http://dx.doi.org/10.1016/j.toxlet.2020.08.004DOI Listing
October 2020

Schizandrin B Mitigates Rifampicin-Induced Liver Injury by Inhibiting Endoplasmic Reticulum Stress.

Biol Pharm Bull 2020 Jan 30;43(1):145-152. Epub 2019 Oct 30.

Nanjing University of Chinese Medicine.

Schisandra chinensis is widely used and effective in protecting liver. There are many mechanisms of drug-induced hepatocyte injury, among which endoplasmic reticulum (ER) stress-induced cell injury plays an important role. However, little is known about whether schisandra chinensis can inhibit rifampicin (RFP)-induced hepatocyte injury by affecting ER stress. In our study, firstly, L02 cells were treated with different concentrations of RFP for different time intervals, and the apoptosis, survival rate and endoplasmic reticulum stress gene and protein expressions of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), activating transcription factor (ATF)4, C/EBP-homologus protein (CHOP), ATF6, arginine-rich, mutated in early stage tumors (ARMET), p-inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP-1) were measured. We found that RFP increased apoptosis of L02 cells, decreased cell survival, and increased the gene and protein expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET, p-IRE1 and XBP-1, suggesting that RFP could induce hepatocyte injury, and the degree of injury was positively correlated with the dose and time of RFP. Next, we treated RFP-damaged hepatocytes with schizandrin B. We found that schizandrin B increased cell survival rate in dose-dependent and time-dependent manner, decreased cell apoptosis rate, and reduced protein and gene expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET and XBP-1. These results indicate that schizandrin B alleviates RFP-induced injury in L02 cells by inhibiting ER stress.
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http://dx.doi.org/10.1248/bpb.b19-00725DOI Listing
January 2020

Curcumin relieves paraquat‑induced lung injury through inhibiting the thioredoxin interacting protein/NLR pyrin domain containing 3‑mediated inflammatory pathway.

Mol Med Rep 2019 Dec 23;20(6):5032-5040. Epub 2019 Aug 23.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.

When paraquat (PQ) enters the human body, it increases oxidative stress and inflammation, ultimately resulting in acute lung injury (ALI). Curcumin, a naturally occurring compound, has been reported to ameliorate PQ‑induced ALI; however, the underlying molecular mechanisms remain unclear. In the present study, normal lung fibroblasts (WI‑38VA13) were treated with 10 µmol/l PQ for 48 h, followed by a further 48 h incubation with 300 µmol/l curcumin. Cells were then harvested to determine their viability. Flow cytometry was performed to analyze the levels of reactive oxygen species (ROS) and the rate of apoptosis. The levels of apoptotic proteins and activation of the thioredoxin interacting protein/NLR pyrin domain containing 3 (TXNIP/NLRP3) axis were measured via reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Proinflammatory cytokine levels were examined using enzyme‑linked immunosorbent assays. Finally, the expression levels of Notch1, extracellular signal‑regulated kinase 1/2 (ERK1/2) and phosphorylated‑ERK1/2 were evaluated via western blotting. Following treatment with curcumin, PQ‑induced increases in ROS levels and apoptosis were significantly attenuated, and Bcl‑2 expression levels were upregulated, whereas those of Bax were downregulated. It was also observed that curcumin treatment downregulated the expression levels of TXNIP, NLRP3, interleukin (IL)‑1β and IL‑18, and downstream caspase‑1 compared with PQ treatment alone. Curcumin significantly attenuated the upregulation of Notch1 without affecting ERK1/2 phosphorylation. The present findings suggested that the inhibitory effects of curcumin on TXINP1 may inhibit activation of the NLRP3 inflammasome, subsequently suppressing the upregulation of proinflammatory cytokines and ultimately improving PQ‑induced ALI.
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http://dx.doi.org/10.3892/mmr.2019.10612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854544PMC
December 2019

Advances in nanomaterials for use in photothermal and photodynamic therapeutics (Review).

Mol Med Rep 2019 Jul 9;20(1):5-15. Epub 2019 May 9.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.

Nanomaterials play crucial roles in the diagnosis and treatment of diseases. Photothermal and photodynamic therapy, as two minimally invasive therapeutic methods, have promising potential in the diagnosis and prevention of cancer. Recently, many photothermal materials (such as noble metal material, transition metal sulfur oxides, carbon material and upconversion nanomaterial) and photodynamic materials (such as phthalein cyanogen, porphyrins and other dye molecules) have been applied in photothermal therapy (PTT) and photodynamic therapy (PDT). Moreover, as nanomaterials have suitable biocompatibility, these materials have been applied in cancer therapy. In the present review, we summarized the effects of different material types, synthesis methods, material morphologies and surface modifications on the outcomes of cancer therapy. The application of nanomaterials in PTT and PDT was introduced and the advantages and disadvantages of PTT and PDT in the prevention of cancer were discussed. Finally, we discussed the application of nanomaterials in the combination of PTT and PDT in cancer treatment.
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http://dx.doi.org/10.3892/mmr.2019.10218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579972PMC
July 2019

Retrospective study of clinical features and prognosis of edaravone in the treatment of paraquat poisoning.

Medicine (Baltimore) 2019 May;98(19):e15441

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China.

To observe whether edaravone can protect organs and inhibit pulmonary fibrosis in patients with paraquat poisoning and to provide a method for clinical intervention for paraquat poisoning.Forty-four cases of paraquat poisoning were collected from March 2011 to December 2017 in our hospital. Eighteen cases from March 2011 to November 2013 did not receive edaravone treatment and were considered the control group, and 26 cases from January 2014 to December 2017 were treated with edaravone and were considered the observation group. Injuries to the central nervous system, heart, liver, kidney, and digestive system were evaluated on at 24 hours, 3 days, and 7 days after hospitalization. The expression of serum inflammatory factors (interleukin [IL]-6, IL-10, tumor necrosis factor-α [TNF-α]) and oxidative stress correlation (superoxide dismutase [SOD] and malondialdehyde [MDA]) were assayed at 24 hours, 3 days, and 7 days after being hospitalized. After 7, 14, and 30 days, the changes in pathological lung characteristics in the 2 groups were assessed, and survival rates were calculated.Edaravone significantly increased the serum levels of SOD and obviously markedly reduce the serum levels of IL-6, IL-10, TNF-α, and MDA in patients poisoned with paraquat (P < .05). Edaravone significantly protected the liver (P = .021), cardiovascular (P = .031), and renal (P = .028) organs of patients from paraquat poisoning-induced injury after 7 days but had no significant protection or improvement on respiratory and digestive tract damage. Edaravone delayed the occurrence of pulmonary fibrosis and increase the survival time of patients at 7 and 14 days (P < .05). However, the 1-month follow-up found that edaravone did not reduce pulmonary fibrosis (77.8% vs 73.1%, P = .615) and did not increase the survival rate of the patients (61.1% vs 65.3%, P = .853).Edaravone is beneficial for protecting the kidneys and liver from paraquat poisoning through reducing oxidative stress and inhibiting inflammatory response. It can also inhibit the pulmonary fibrosis process and prolong the survival time of the patients. However, no significant improvements were seen in the probability of pulmonary fibrosis and the survival rate.
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http://dx.doi.org/10.1097/MD.0000000000015441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531030PMC
May 2019

E3 ubiquitin ligase tripartite motif 7 positively regulates the TLR4-mediated immune response via its E3 ligase domain in macrophages.

Mol Immunol 2019 05 28;109:126-133. Epub 2019 Mar 28.

Department of Emergency Medicine, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China; Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address:

Members of the tripartite motif (TRIM) family as E3 ubiquitin ligases have been regarded as critical regulators of innate immunity and antiviral response. However, the role of TRIM7 is still elusive. Here, we provide evidence for the importance of TRIM7 in regulation of the TLR4-mediated innate response. In detail, we find that TRIM7 is highly expressed in antigen-presenting cells like macrophages. Knockdown of TRIM7 clearly inhibits the LPS-induced production of IFN-β, TNF-α and IL-6 in macrophages. Conversely, forced expression of TRIM7 could exert an opposite effect on these pro-inflammatory cytokines. Further analysis indicates that such effect is mediated by the TLR4-associated signaling pathways including MAPKs, NF-κB and IRF3-involved pathways. Truncation of the E3 ligase domain on TRIM7 may reduce the production of pro-inflammatory cytokines, suggesting a critical role of this domain in the regulation of LPS-initiated innate response. Taken together, we report here that TRIM7 may facilitate the TLR4-mediated innate response via its E3 ligase domain in macrophages, which provides new insight into the mechanistic role of TRIM7 in innate immunity.
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http://dx.doi.org/10.1016/j.molimm.2019.01.015DOI Listing
May 2019

Protective effect of ginsenoside Rg1 on LPS-induced apoptosis of lung epithelial cells.

Mol Immunol 2021 Aug 22;136:168-174. Epub 2018 Nov 22.

Department of Emergency Medicine, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, PR China. Electronic address:

Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity in the critical care units. Though, it was commonly accepted that inflammation and apoptosis of lung epithelial cells played an essential role in the pathogenesis of ALI, the underlying mechanism remain unknown. In our study, we found that LPS-induced cell apoptosis could be counteracted by elevated cell autophagy. In LPS-treated MLE-12 cells, suppression of autophagy via 3-MA could aggravate LPS-induced apoptosis, while activation of autophagy via Rapamycin could effectively impair the apoptosis of MLE-12 cells induced by LPS. In order to further discover the molecular regulation mechanism between apoptosis and autophagy in LPS-treated MLE-12 cells, we demonstrated that autophagy could induced the expression of Nrf2, followed with the decrease of p-p65. Targeted inhibition of Nrf2 could induce enlarged cell apoptosis via increasing the level of p-p65. In addition, we demonstrated that ginsenoside Rg1 protected MLE-12 cells from LPS-induced apoptosis via augmenting autophagy and inducing the expression of Nrf2. Our data implicates that activation of autophagy and Nrf2 by ginsenoside Rg1 may provide a preventive and therapeutic strategy for ALI.
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http://dx.doi.org/10.1016/j.molimm.2018.11.003DOI Listing
August 2021

Melatonin protects against myocardial ischemia-reperfusion injury by elevating Sirtuin3 expression and manganese superoxide dismutase activity.

Free Radic Res 2018 Aug;52(8):840-849

a Department of Emergency Medicine , Jinling Hospital, Medical School of Nanjing University , Nanjing , PR China.

Myocardial ischemia-reperfusion (MI/R) injury is a crucial cause for mortality throughout the world. Recent studies indicated that melatonin might exert profound cardio-protective effect in MI/R injury. However, the underlying mechanisms are not completely understood. In the current study, we aimed to explore the potential effect of melatonin in the pathological process of MI/R. Both in vivo MI/R model and in vitro H9c2 cell line simulated I/R (SIR) model were applied with or without melatonin supplementation. We found that Sirtuin3 (Sirt3) expression and activity were markedly decreased under MI/R and SIR conditions. Melatonin treatment significantly increased myocardial Sirt3 expression, and alleviated MI/R-induced cardiac morphology changes and cardiac dysfunction, as well as myocardial apoptosis level. In addition, DHE and JC-1 staining results demonstrated that melatonin reduced mitochondrial reactive oxygen species (ROS) generation and restored ATP production after SIR injury via elevating Sirt3 expression. By using siRNA targeting Sirt3, we confirmed that the beneficial effects of melatonin were dependent on Sirt3, which in turn deacetylated and activated manganese superoxide dismutase (MnSOD). Collectively, the current study demonstrated the protective effect of melatonin against MI/R injury via alleviating myocardial oxidative stress. Moreover, these beneficial effects were associated with the deacetylation modification of Sirt3 on MnSOD.
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http://dx.doi.org/10.1080/10715762.2018.1461215DOI Listing
August 2018

Aortic Dissection Presenting as Septic Shock: A Case Report and Literature Review.

Case Rep Emerg Med 2018 14;2018:9706290. Epub 2018 Feb 14.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.

Acute aortic dissection is a life-threatening clinical emergency, which mostly occurs in aged patients and presents with sharp chest pain. In this paper, we reported a case of acute aortic dissection, which induced septic shock in a young woman, without typical chest pain. The septic shock was possibly due to the bacterial translocation caused by aortic dissection-induced intestinal ischemia and intestinal epithelial barrier dysfunction. Our case appeared as the first case report of aortic dissection presenting as septic shock. This case is rare but can serve as a reminder that aortic dissection may be accompanied by septic shock, and this could result in a grave outcome.
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http://dx.doi.org/10.1155/2018/9706290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832074PMC
February 2018

[Epidemiology characteristics of crawfish related rhabdomyolysis in Nanjing, 2016: a multicenter retrospective investigation].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2017 Sep;29(9):805-809

Department of Emergency, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China (Ma SL, Xu CS, Liu SQ, Hu ZF, Liu WG); Department of Emergency, Jiangsu Provincial People's Hospital, Najing 210029 Jiangsu, China (Zhang JS, Chen XF); Department of Emergency, Nanjing General Hospital, Nanjing 210002, Jiangsu, China (Nie SN); Department of Emergency, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu, China (Zhang J, Sha DJ); Department of Emergency, Jiangsu Provincial Traditional Chinese Medicine Hospital, Nanjing 210004, Jiangsu, China (Li JJ); Department of Emergency, Jiangsu Provincial Hospital on Integration of Chinese and Western Medicine, Nanjing 210028, Jiangsu, China (Ni HB); Department of Emergency, the First Hospital of Nanjing, Nanjing 210006, Jiangsu, China (Qin HD); Department of Emergency, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, China (Gao Y); Department of Critical Care Medicine, Pukou Hospital of Nanjing, Nanjing 210031, Jiangsu, China (Wang W); Department of Emergency, Jiangbei People's Hospital, Nanjing 210048, Jiangsu, China (Wu CF); Department of Emergency, Nanjing Jiangning Hospital, Nanjing 211100, Jiangsu, China (Yu Z); Department of Emergency, Nanjing Tongren Hospital, Nanjing 211102, Jiangsu, China (Zhu CJ). Corresponding author: Xu Changsheng, Email:

Objective: To investigate the epidemiology characteristics of crawfish related rhabdomyolysis (RM) in Nanjing, 2016.

Methods: Outpatient and inpatient electronic medical system of 21 hospitals in Nanjing during 2016 were retrospectively searched, and all the patients diagnosed with RM were selected. The patients with none crayfish-related RM was excluded. The epidemiology characteristics were depicted. The geographic information system (GIS) was used to collect, manage and analyze the spatial data, to visualize it, to analyze the spatial distribution features of the disease, and to explore the cause of disease prediction. GeoDa 1.8 software was used to analyze the global and local spatial auto-correlation.

Results: A total of 1 183 patients with crawfish related RM were initially screened, excluding 59 patients with RM caused by trauma, severe exercise, heat stroke, myositis, poisoning, drugs, and genetic diseases, and 1 124 patients were enrolled. The proportion of men was 36.48% (410/1 124) with an incidence of 12.54/100 thousands; while of women was 63.52% (714/1 124) with an incidence of 21.86/100 thousands. The median age at onset was 34 (28, 43) years. From July to August, the incidence of crawfish related RM was the highest, accounting for 96.53% of the total number of cases. The top four incidence areas were Pukou (41.54/100 thousands), Jianye (25.94/100 thousands), Qixia (25.73/100 thousands), Gulou (25.04/100 thousands), all of which were adjacent to the Yangtze River. Global spatial autocorrelation analysis showed: Moran I = 0.427, Z = 2.646, P = 0.003, suggesting that the crawfish related RM had positive spatial autocorrelation. The results showed that the spatial structure of crawfish related RM existed in Nanjing in 2016. Local spatial autocorrelation analysis showed that the "high-high" concentration areas were Pukou, Jianye and Liuhe. The incidences of above three areas which were the Nanjing section of the lower reaches of the Yangtze River flowed through the region and surrounding areas were higher than the overall incidence of Nanjing.

Conclusions: The prevalence of crawfish related RM in Nanjing during 2016 had an obvious region-concentrated character and global spatial autocorrelation with the high prevalent regions mainly concentrated in the urban areas adjacent to the Yangtze River.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2017.09.008DOI Listing
September 2017

The Fab Fragment of a Human Anti-Siglec-9 Monoclonal Antibody Suppresses LPS-Induced Inflammatory Responses in Human Macrophages.

Front Immunol 2016 26;7:649. Epub 2016 Dec 26.

Department of Infectious Disease, Anhui Medical University Affiliated with Bayi Clinical College, Hefei, China; Institute of Liver Disease, Nanjing Jingdu Hospital, Nanjing, China.

Sepsis is a major cause of death for hospitalized patients and is characterized by massive overreaction of immune responses to invading pathogens which is mediated by cytokines. For decades, there has been no effective treatment for sepsis. Sialic acid-binding, Ig-like lectin-9 (Siglec-9), is an immunomodulatory receptor expressed primarily on hematopoietic cells which is involved in various aspects of inflammatory responses and is a potential target for treatment of sepsis. The aim of the present study was to develop a human anti-Siglec-9 Fab fragment, which was named hS9-Fab03 and investigate its immune activity in human macrophages. We began by constructing the hS9-Fab03 prokaryotic expression vector from human antibody library and phage display. Then, we utilized a multitude of assays, including SDS-PAGE, Western blotting, ELISA, affinity, and kinetics assay to evaluate the binding affinity and specificity of hS9-Fab03. Results demonstrated that hS9-Fab03 specifically bind to Siglec-9 antigen with high affinity, and pretreatment with hS9-Fab03 could attenuate lipopolysaccharide (LPS)-induced TNF-α, IL-6, IL-1β, IL-8, and IFN-β production in human PBMC-derived macrophages, but slightly increased IL-10 production in an early time point. We also observed similar results in human THP-1-differentiated macrophages. Collectively, we prepared the hS9-Fab03 with efficient activity for blocking LPS-induced pro-inflammatory cytokines production in human macrophages. These results indicated that ligation of Siglec-9 with hS9-Fab03 might be a novel anti-inflammatory therapeutic strategy for sepsis.
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http://dx.doi.org/10.3389/fimmu.2016.00649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183739PMC
December 2016

A Human Anti-Toll Like Receptor 4 Fab Fragment Inhibits Lipopolysaccharide-Induced Pro-Inflammatory Cytokines Production in Macrophages.

PLoS One 2016 19;11(1):e0146856. Epub 2016 Jan 19.

Huadong Medical Institute of Biotechniques, Nanjing 210002, China.

The results of clinical and experimental studies suggest that endotoxin/toll-like receptor 4 (TLR4)-mediated proinflammatory and profibrotic signaling activation is critical in the development of hepatic fibrosis. However, studies examining the role of specific TLR4 inhibitor are still lacking. The present study was aimed to prepare a human anti-TLR4 Fab fragment, named hTLR4-Fab01, and to explore its immune activity. We screened the positive clone of anti-human TLR4 phagemid from a human phage-display antibody library using recombinant TLR4 protein, which was used as template cDNA for the amplification of variable regions of the heavy (VH) chain and light chain (VL), then coupled with highly conserved regions of the heavy chain domain 1 (CH1) and the light chain (CL), respectively. Thus, the prokaryotic expression vector pETDuet-1 of hTLR4-Fab01 was constructed and transformed into Escherichia coli (E. coli) BL21. The characteristic of hTLR4-Fab01 was examined by SDS-PAGE, Western blotting, ELISA, affinity and kinetics assay. Further, our data demonstrate that hTLR4-Fab01 could specifically bind to TLR4, and its treatment obviously attenuated the proinflammatory effect, characterized by less LPS-induced TNF-α, IL-1, IL-6 and IL-8 production in human macrophages. In conclusion, we have successfully prepared the hTLR4-Fab01 with efficient activity for blocking LPS-induced proinflammatory cytokines production, suggesting that the hTLR4-Fab01 may be a potential candidate for the treatment of hepatic fibrosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146856PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718644PMC
July 2016

[A Meta analysis on the associations between air pollution and respiratory mortality in China].

Zhonghua Liu Xing Bing Xue Za Zhi 2015 Aug;36(8):889-95

Department of Emergency Medicine, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China; Email:

Objective: To analyze the associations between air pollution and adverse health outcomes on respiratory diseases and to estimate the short-term effects of air pollutions [Particulate matter with particle size below 10 microns (PM(10)), PM(10) particulate matter with particle size below 2.5 microns (PM(2.5)), nitrogen dioxide (NO₂), sulphur dioxide (SO₂) and ozone (O₃)] on respiratory mortality in China.

Methods: Data related to the epidemiological studies on the associations between air pollution and adverse health outcomes of respiratory diseases that published from 1989 through 2014 in China, were collected by systematically searching databases of PubMed, SpringerLink, Embase, Medline, CNKI, CBM and VIP in different provinces of China. Short-term effects between (PM(10), PM(2.5), NO₂, SO₂, O₃) and respiratory mortality were analyzed by Meta-analysis method, and estimations were pooled by random or fixed effect models, using the Stata 12.0 software.

Results: A total of 157 papers related to the associations between air pollution and adverse health outcomes of respiratory diseases in China were published, which covered 79.4% of all the provinces in China. Results from the Meta-analysis showed that a 10 µg/m³ increase in PM10, PM(2.5), NO₂, SO₂, and O₃was associated with mortality rates as 0.50% (95% CI: 0-0.90%), 0.50% (95% CI: 0.30%-0.70%), 1.39% (95% CI: 0.90%-1.78%), 1.00% (95% CI: 0.40%-1.59%) and 0.10% (95% CI: -1.21%-1.39%) in respiratory tracts, respectively. No publication bias was found among these studies.

Conclusion: There seemed positive associations existed between PM(10)/PM(2.5)/NO₂/SO₂and respiratory mortality in China that the relationship called for further attention on air pollution and adverse health outcomes of the respiratory diseases.
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August 2015

Chitosan layered gold nanorods as synergistic therapeutics for photothermal ablation and gene silencing in triple-negative breast cancer.

Acta Biomater 2015 Oct 17;25:194-204. Epub 2015 Jul 17.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China. Electronic address:

Unlabelled: Small interfering RNAs (siRNAs) are extensively studied due to their promising potential as therapeutic agents for a wide variety of diseases, including cancer. However, efficient delivery of siRNAs to target cells and tissues is problematic due to a lack of suitable delivery vehicles. In this work, we developed a layer-by-layer assembled chitosan-gold nanorods (Chit-Au NRs) siRNA delivery system to overcome biological barriers upon systemic injection. This platform was able to protect siRNAs form degradation upon exposure to ribonuclease (RNase) or serum. Confocal and intravital microscopy reveals that Chit-Au NRs/siRNAs are successfully delivered into target cells and tissue, and can efficiently escape from endosomal/lysosomal structures. Furthermore, Chit-Au NRs/siRNA were found to accumulate in high levels in tumor tissue. The delivery system was able to inhibit the oncogene expression (pyruvate kinase isozymeM2, PKM2) in MDA-MB-231 triple negative breast cancer cells, resulting in suppression of cell proliferation and migration. Moreover, the anticancer efficacy was further enhanced through NR-mediated photothermal ablation. In conclusion, the synergistic therapeutic properties of Chit-Au NRs/siRNA enable effective suppression of cancer growth.

Statement Of Significance: Small interfering RNA (siRNA) therapy has promising therapeutic applications, since the expression of any protein can be suppressed. However the successful implementation of siRNA has been challenging, due to rapid degradation, poor intracellular uptake and insufficient endosomal escape. Here, we have developed a gold nanorod/chitosan-based delivery vehicle for siRNA therapy. This platform successfully overcomes the afore-mentioned challenges and can simultaneously be used for photothermal therapy, due to the optical properties of gold nanorods. We show that the anticancer activity is dramatically improved by combining thermal therapy with gene silencing. Furthermore, the Au NRs carrier shows high accumulation in tumor tissue and high transfection efficiency. This manuscript has been reviewed and approved by all co-authors. The research has not been disclosed or published and is not under consideration for publication elsewhere. We would appreciate if the manuscript could be reviewed and considered for publication in Acta BIOMATERIALIA.
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http://dx.doi.org/10.1016/j.actbio.2015.07.026DOI Listing
October 2015

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

Mol Med Rep 2015 Jul 24;12(1):1091-7. Epub 2015 Mar 24.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.
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http://dx.doi.org/10.3892/mmr.2015.3537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438944PMC
July 2015

Protective effects of intestinal trefoil factor (ITF) on gastric mucosal epithelium through activation of extracellular signal-regulated kinase 1/2 (ERK1/2).

Mol Cell Biochem 2015 Jun 17;404(1-2):263-70. Epub 2015 Mar 17.

Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, People's Republic of China.

The rapid repair of gastric mucosa is critical upon exposure to injurious agents. Intestinal trefoil factor (ITF) is a member of the trefoil factor family domain peptides, which play an important role in the cytoprotection of gastric epithelium. However, the underlying molecular mechanisms that are responsible for ITF-induced gastric epithelial repair remain unclear. In the present study, we demonstrate that ITF enhances the proliferation and migration of GES-1 gastric endothelial cells in a dose- and time-dependent manner through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Furthermore, the ITF-mediated protection of GES-1 cells from a NS398 (nonsteroidal anti-inflammatory drug) was dependent on the ERK1/2 signaling pathway. Taken together, the results provide a mechanistic explanation for ITF-mediated protection of gastric epithelial mucosa cells, suggesting that activation of the ERK1/2 signaling pathway may provide a new therapeutic strategy for repairing gastric injury.
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http://dx.doi.org/10.1007/s11010-015-2386-2DOI Listing
June 2015

Spontaneous type B aortic dissection in antepartum gemellary pregnancy and endovascular repair.

Int J Clin Exp Med 2014 15;7(11):4249-52. Epub 2014 Nov 15.

Department of Emergency Medicine, Nanjing Jinling Hospital Jiangsu, China.

Background: It has been found that 50% of all aortic dissections can be attributable to pregnancy in women younger than 45 years of age. An estimated 30% of cases are type B, with half occurring in the antepartum period. To date type B aortic dissection has rarely been reported in gemellary pregnancies.

Case: A 24-year-old primigravida at 36 weeks of gemellary gestation presented symptoms of severe and persistent chest pain for 1 day, before suffering the acute type B aortic dissection. The primigravida was treated with immediate cesarean section and endovacular stent graft placement.

Conclusion: Aortic dissection is a rare complication of pregnancy, especially in gemellary pregnancies. Pregnancy is considered an independent risk factor for aortic dissection and endovascular repair may be an ideal option for the treatment of complicated type B aortic dissection during pregnancy, with reduced maternal and fetal mortality.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276197PMC
December 2014

[Logistic regression analysis on risk factors of cerebral hemorrhage complicated with stress ulcer].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2014 Oct;26(10):730-3

Department of Emergency Medicine, Nanjing General Hospital of Nanjing Military Command, PLA, Nanjing 210002, Jiangsu, China, Corresponding author: Nie Shinan, Email:

Objective: To explore the related risk factors of cerebral hemorrhage complicated with stress ulcer (SU).

Methods: The clinical data of 1 185 patients with cerebral hemorrhage admitted to Department of Emergency Medicine of Nanjing General Hospital from March 2006 to March 2014 were retrospectively analyzed. Patients were divided into two groups according to whether patients complicated with SU or not. Data was collected within 8 hours after admission in two groups including gender, age, amount of bleeding, the bleeding site (basal ganglia, thalamus, brainstem, brain lobe, ventricle, subarachnoid, and cerebellum), disturbance of consciousness, acute physiology and chronic health evaluation II (APACHEII) score, systolic blood pressure (SBP), history of hypertension, and history of cerebral hemorrhage. The statistically significant risk factors found using univariate analysis was selected and was analyzed to find independent risk factors with multivariate logistic regression analysis. The receiver operating characteristic curve (ROC curve) was plotted to analyze the independent risk factors and evaluate their power of test.

Results: 1 185 patients with cerebral hemorrhage were enrolled in the study, 293 cases occurred SU, accounting for 24.7%, and 892 cases without SU, which accounted for 75.3%. As shown by univariate analysis, risk factors for cerebral hemorrhage complicated with SU included age, amount of bleeding, the bleeding site, disturbance of consciousness, APACHEII score, SBP. As to the site of bleeding, brain, thalamus, brainstem hemorrhage complicated with SU were higher proportion, 45.3% (43/95), 39.1% (63/161), 36.9% (48/130), which were significantly higher than those of the lobes of the brain [26.2% (33/126)], cerebellum [18.8% (15/80)], basal ganglia [16.1% (78/485)], arachnoid the inferior vena cava [12.0% (13/108)]. Multivariate logistic regression analysis showed that amount of bleeding [odds ratio (OR)=3.305, P=0.001, 95% confidence interval (95%CI) 2.213-48.634], the bleeding site (OR=1.762, P=0.008, 95%CI 0.123-2.743), SBP (OR=1.223, P=0.034, 95%CI 0.245-2.812) were independent risk factors of cerebral hemorrhage complicated with SU. The area under the ROC curve (AUC) of amount of bleeding and SBP were 0.846 and 0.597, suggesting that amount of bleeding has moderate diagnostic value and SBP has low diagnostic value.

Conclusions: Cerebral hemorrhage patients with large amount of bleeding, the bleeding site in the ventricle, thalamus or brainstem, high SBP are of great risk. We should lower blood pressure and give preventive treatment for SU as soon as possible.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2014.10.011DOI Listing
October 2014

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage.

Int J Oncol 2014 Sep 27;45(3):1123-32. Epub 2014 Jun 27.

Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.

Intestinal trefoil factor (ITF, also named as trefoil factor 3, TFF3) is a member of the TFF-domain peptide family, which plays an essential role in the regulation of cell survival, cell migration and maintains mucosal epithelial integrity in the gastrointestinal tract. However, the underlying mechanisms and associated molecules remain unclear. The aim of this study was to explore the protective effects of ITF on gastric mucosal epithelium injury and its possible molecular mechanisms of action. In the present study, we show that ITF was able to promote the proliferation and migration of GES-1 cells via a mechanism that involves the PI3K/Akt signaling pathway. Western blot results indicated that ITF induced a dose- and time-dependent increase in the Akt signaling pathway. ITF also plays an essential role in the restitution of GES-1 cell damage induced by lipopolysaccharide (LPS). LPS induced the apoptosis of GES-1 cells, decreased cell viability significantly (P<0.01) and led to epithelial tight junction damage, which is attenuated via ITF treatment. The protective effect of ITF on the integrity of GES-1 was abrogated by inhibition of the PI3K/Akt pathway. Taken together, our results demonstrate that ITF promotes the proliferation and migration of gastric mucosal epithelial cells and preserves gastric mucosal epithelial integrity after damage is mediated by activation of the PI3K/Akt signaling pathway. This study suggested that the PI3K/Akt pathway could act as a key intracellular pathway in the gastric mucosal epithelium that may serve as a therapeutic target to preserve epithelial integrity during injury.
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http://dx.doi.org/10.3892/ijo.2014.2527DOI Listing
September 2014

Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis.

Int J Mol Med 2014 May 25;33(5):1097-109. Epub 2014 Feb 25.

Immunology and Reproductive Biology Laboratory, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.

Acute lung injury may lead to fibrogenesis. However, no treatment is currently available. This study was conducted to determine the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-1 and its receptor CXC chemokine receptor (CXCR)4 have been shown to participate in mobilizing MSCs. Adenovirus carrying the CXCR4 gene was used to transfect MSCs in order to increase the engraftment numbers of MSCs at injured sites. Histological examination data demonstrated that the engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis. The results showed that engraftment of MSCs almost differentiated into myofibroblasts, but rarely differentiated into lung epithelial cells. Additionally, it was demonstrated that activated canonical Wnt/β-catenin signaling in injured lung tissue regulated the myofibroblast differentiation of MSCs in vivo. The in vitro study results demonstrated that activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblast markers; however, this process was attenuated by Wnt antagonist DKK1. Therefore, the results demonstrated that the aberrant activation of Wnt signaling induces the myofibroblast differentiation of engrafted MSCs, thus contributing to pulmonary fibrosis following lung injury.
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http://dx.doi.org/10.3892/ijmm.2014.1672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020487PMC
May 2014

Pneumomediastinum from acute inhalation of chlorine gas in 2 young patients.

Am J Emerg Med 2011 Mar 13;29(3):357.e1-4. Epub 2010 Jul 13.

Department of Emergency Medicine, Nanjing Jinling Hospital and Nanjing University College of Medicine, Jiangsu, China.

Trichloroisocyanuric acid is a high-efficiency and-low toxicity fungicide and bleach. It is commonly used as disinfectant for industrial circulating water, swimming pools, restaurants, and other public places in China. When trichloroisocyanuric acid is put into water, chlorine gas is produced. Chlorine gas is a potent pulmonary irritant that causes acute damage in both the upper and lower respiratory tracts (J Toxicol Clin Toxicol. 1998;36(1-2):87-93). Pneumomediastinum is a rare complication in patients with acute chlorine gas poisoning. A small amount of gas can be asymptomatic, but a large amount of gas entering the mediastinum suddenly will lead to respiratory and circulatory disorder, mediastinal swing, or even cardiopulmonary arrest. Severe chlorine gas poisoning patients usually need mechanical ventilation; if the pneumomediastinum is not found on time, threat to life would be greatly increased. It requires a high index of suspicion for diagnosis and rapid treatment. The proper use of ventilator, timely and effective treatment of original disease, and multiple system organ support had significant impact on the prognosis. The pneumomediastinum case secondary to inhalation of chlorine gas that we report here should remind all emergency department physicians to maintain a high index of suspicion for this disease and seek immediate and proper intervention when treating patients with acute chlorine gas poisoning, once diagnosed, especially in younger patients.
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http://dx.doi.org/10.1016/j.ajem.2010.04.007DOI Listing
March 2011

[Changes of rat gastric mucosal barrier under stress conditions].

Zhonghua Nei Ke Za Zhi 2002 Jun;41(6):374-7

Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433,China.

OBJECTIVE To explore the changes of rat gastric mucosal barrier under conditions of water immersion restraint stress. METHODS Eighty rats were randomly divided into Group A (20 rats), B (40 rats) and C (20 rats) after being fasted for 24 hours. And then Group A was divided into two subgroups with ten rats in each. The two subgroups in Group A were given normal saline or omeprazole respectively while under the stress condition. The changes of gastric acid or bicarbonate secretion were determined. Group B (40 rats) were randomly divided into four subgroups,which were subgroup control, 1h, 2h and 4h after beginning of the stress. The quantity of glandular mucosal adherent mucus, the thickness of mucus gel layer and ulcer index were measured after stress in Group B. The glandular mucosal samples were labeled by Lanthanum and observed by transmission electromicroscopy. Group C was randomly divided into two subgroups in the same way with Group A. And each subgroup received normal saline or omeprazole respectively H(+) loss in gastric lumen was calculated by determining the difference of acidity between lavage and drainage fluid H(+) concentration. RESULTS It was found that gastric alkaline secretion decreased progressively (P < 0.05), while gastric acid secretion increased progressively under stress conditions (P < 0.05). The mucus quantity(A/g) in the four subgroups in Group B were 0.137 +/- 0.030, 0.143 +/- 0.012, 0.066 +/- 0.016 and 0.016 +/- 0.016 respectively. The mucus gel thickness(microm) were 71.08 +/- 5.85, 74.50 +/- 12.85, 57.63 +/- 6.45 and 51.35 +/- 2.84 respectively. The ulcer index were 0.2 +/- 0.1,0.4 +/- 0.1,5.2 +/- 1.3 and 10.0 +/- 0.5 respectively. Statistics showed that the mucus quantity was correlated with the mucus gel thickness positively(r = 0.89), while either of them was correlated with the ulcer index negatively(r = 0.85 and "r = 0.83). And it was also found that Lanthanum rarely stained the glandular mucosa in control subgroup, while heavily in stress subgroups. In the subgroup receiving normal saline in Group C, within 5 hours after the beginning of stress, the amount of H(+) loss per hour(micromol) was 2.03 +/- 0.12, 2.00 +/- 0.20, 1.93 +/- 0.49, 2.70 +/- 0.44 and 3.37 +/- 0.35 respectively. It was demonstrated that the amount of H(+) loss was stable within 2h after stress, then increased obviously in normal saline subgroup significantly (P < 0.01). In omeprazole subgroup, the amount of H(+) loss (micromol) was 7.46 +/- 1.22, 4.56 +/- 0.35, 3.11 +/- 0.81, 2.32 +/- 1.42 and 2.13 +/- 1.60, which decreased progressively, however still higher than those in normal saline subgroup (P "< 0.01). CONCLUSIONS The results suggest that gastric bicarbonate secretion is inhibited; gastric barrier is damaged; and hydrogen permeability through gastric mucosal barrier increases under stress conditions.
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June 2002

[Role of the pS(2) in gastric mucosa adaptative cytoprotection from stress].

Zhonghua Yi Xue Za Zhi 2002 Feb;82(3):172-5

Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Center of Gastroenterology and Key Laboratory of PLA, Shanghai 200433, China.

Objective: To determine the expression of pS(2) (a member of trefoil peptides) in gastric mucosal of rats undergone WRS, and to probe the role of pS(2) in adaptive cytoprotection.

Methods: Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 days. Gastric mucosal blood flow (GMBF) was measured by LDF-3 Flowmeter. The degree of the gastric mucosal lesions (UI) was evaluated grossly and histologically. The expression of pS(2) was determined by RT-PCR and immunohistochemistry.

Results: (1) WRS applied once produced numerous gastric mucosal erosions. UI gradually declined and GMBF restored on 3 d, 5 d after stress. UI was reduced to 20.8% and GMBF increased up to 94.5% of normal value. The expression of pS(2) was increased during the healing of stress-induced ulceration. The same results were observed by immunohistochemistry (0.50 +/- 0.13 vs 0.70 +/- 0.11, P < 0.01). (2) With repeated WRS, the adaptative cytoprotection against stress was developed. UI after four consecutive WRS was 22% of UI after one WRS. GMBF after four consecutive was 94.2% of normal value. Cell proliferation in the neck regions of gastric glands was activated. The expression of pS(2) was increased by using RT-PCR (0.37 +/- 0.02 vs 0.77 +/- 0.01, P < 0.01) and immunohistochemistry (0.55 +/- 0.04 vs 2.46 +/- 0.08, P < 0.01).

Conclusion: Increased expression of pS(2) could play an important role in adaptation of gastric mucose developed after repeated WRS.
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February 2002
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