Publications by authors named "Jingjing Ding"

71 Publications

The Immune Subtypes and Landscape of Gastric Cancer and to Predict Based on the Whole-Slide Images Using Deep Learning.

Front Immunol 2021 28;12:685992. Epub 2021 Jun 28.

Department of General Practice, Tongren Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

Background: Gastric cancer (GC) is a highly heterogeneous tumor with different responses to immunotherapy. Identifying immune subtypes and landscape of GC could improve immunotherapeutic strategies.

Methods: Based on the abundance of tumor-infiltrating immune cells in GC patients from The Cancer Genome Atlas, we used unsupervised consensus clustering algorithm to identify robust clusters of patients, and assessed their reproducibility in an independent cohort from Gene Expression Omnibus. We further confirmed the feasibility of our immune subtypes in five independent pan-cancer cohorts. Finally, functional enrichment analyses were provided, and a deep learning model studying the pathological images was constructed to identify the immune subtypes.

Results: We identified and validated three reproducible immune subtypes presented with diverse components of tumor-infiltrating immune cells, molecular features, and clinical characteristics. An immune-inflamed subtype 3, with better prognosis and the highest immune score, had the highest abundance of CD8+ T cells, CD4+ T-activated cells, follicular helper T cells, M1 macrophages, and NK cells among three subtypes. By contrast, an immune-excluded subtype 1, with the worst prognosis and the highest stromal score, demonstrated the highest infiltration of CD4+ T resting cells, regulatory T cells, B cells, and dendritic cells, while an immune-desert subtype 2, with an intermediate prognosis and the lowest immune score, demonstrated the highest infiltration of M2 macrophages and mast cells, and the lowest infiltration of M1 macrophages. Besides, higher proportion of EVB and MSI of TCGA molecular subtyping, over expression of CTLA4, PD1, PDL1, and TP53, and low expression of JAK1 were observed in immune subtype 3, which consisted with the results from Gene Set Enrichment Analysis. These subtypes may suggest different immunotherapy strategies. Finally, deep learning can predict the immune subtypes well.

Conclusion: This study offers a conceptual frame to better understand the tumor immune microenvironment of GC. Future work is required to estimate its reference value for the design of immune-related studies and immunotherapy selection.
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http://dx.doi.org/10.3389/fimmu.2021.685992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273735PMC
June 2021

Maternal smoking during pregnancy aggravated muscle phenotype in FHL1 offspring mice similar to congenital clubfoot through P2RX7-mediated pyroptosis.

Toxicol Lett 2021 Jul 16;345:54-60. Epub 2021 Apr 16.

Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, 110004, China; Medical Research Center of Shengjing Hospital, China Medical University, Shenyang, 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China. Electronic address:

Congenital clubfoot (CCF) is a common birth defect. Maternal smoking during pregnancy increases the risk of CCF. In previous research, we found muscle phenotypes similar to CCF in four and a half LIM domain protein 1 (FHLI) offspring mice (FHL1). However, the role of P2RX7-mediated pyroptosis in the effect of cigarette smoke (CS) on the skeletal muscle of FHL1 mice during pregnancy is unclear. In the present study, pregnant mice at 11 days of gestation were exposed to CS and male offspring of wild-type (WT) and FHL1 mice were divided into four groups (Control-WT, Control-KO, CS-WT, CS-KO). The histomorphology of lower limb muscles was examined using hematoxylin and eosin (H&E) staining. P2RX7, indicators of pyroptosis (NLRP3, ASC, cleaved-caspase 1, IL-1β), and cytoskeletal proteins (MYBPC2, LDB3) were also detected using immunoblotting. CS exposure during pregnancy aggravated the muscle phenotype similar to CCF in FHL1 offspring mice. FHL1 gene knockout (KO) or CS exposure during pregnancy each activated the expression of P2RX7, cell pyroptosis-related proteins (NLRP3, ASC, cleaved-caspase 1, IL-1β), a muscle injury marker (MYOD1), and cytoskeletal proteins (MYBPC2, LDB3); these two factors had an additive effect. The results showed maternal smoking during pregnancy aggravated muscle phenotype similar to CCF in FHL1 offspring mice through P2RX7-mediated pyroptosis.
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http://dx.doi.org/10.1016/j.toxlet.2021.04.014DOI Listing
July 2021

The Impact of COVID-19 on Primary Care General Practice Consultations in a Teaching Hospital in Shanghai, China.

Front Med (Lausanne) 2021 26;8:642496. Epub 2021 Mar 26.

Department of General Practice, Tongren Hospital, Shanghai, China.

The COVID-19 (2019 novel coronavirus disease) pandemic is deeply concerning because of its massive mortality and morbidity, creating adverse perceptions among patients likely to impact on their overall medical care. Thus, we evaluated the impact of the COVID-19 pandemic on the pattern of primary care consultations within a Shanghai health district. A retrospective observational cohort study was performed, with data analyzed concerning the pattern of patient visits to general practitioners within the Tongren Hospital network (the sole provider of general practice to the population of 700,000). Data from all general practice consultations for adults were collected for the first 6 months of 2020, which included a 60-day lockdown period (January 24-March 24, 2020) and compared to corresponding data from the first 6 months of 2019. We evaluated changes to the numbers and patterns of primary care consultations, including subgroup analysis based on age, sex, and primary diagnosis. A substantial reduction in patient visits, associated with increased median age, was observed during the first wave of the pandemic in the first 6 months of 2020, compared to the same interval during 2019. Additionally, reduced reappointments and waiting times, but increased costs per visit were observed. When analyzed by primary disease diagnosis, patient visits were reduced for all the major systems. The most striking visit reductions were in cardiovascular, respiratory, endocrine, and gastrointestinal diseases. However, psychological disorders were increased following lockdown, but there was also a dramatic fall in consultations for depression. Reduced monthly patient numbers correlated with both rate of reappointment and average waiting time during the first 6 months of both 2019 and 2020, but an inverse correlation was observed between cost per visit and monthly patient numbers. Specifically during the lockdown period, there was ~50% reduced patient visits. The lockdown has had a serious impact on patients' physical and psychological health. Our analysis provides objective health-related data that may inform the current controversy concerning the balance between the detrimental effects of the use of lockdown vs. the use of a more targeted approach to eliminate viral transmission. These data may improve decision-making in medical practice, policy, and education.
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http://dx.doi.org/10.3389/fmed.2021.642496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033033PMC
March 2021

Exercise-induced peptide EIP-22 protect myocardial from ischaemia/reperfusion injury via activating JAK2/STAT3 signalling pathway.

J Cell Mol Med 2021 Apr 12;25(7):3560-3572. Epub 2021 Mar 12.

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

Recent studies have revealed that exercise has myocardial protective effects, but the exact mechanism remains unclear. Studies have increasingly found that peptides play a protective role in myocardial ischaemia-reperfusion (I/R) injury. However, little is known about the role of exercise-induced peptides in myocardial I/R injury. To elucidate the effect of exercise-induced peptide EIP-22 in myocardial I/R injury, we first determined the effect of EIP-22 on hypoxia/reperfusion (H/R)- or H O -induced injury via assessing cell viability and lactate dehydrogenase (LDH) level. In addition, reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) was assessed by fluorescence microscope. Meanwhile, Western blot and TUNEL methods were used to detect apoptosis level. Then, we conducted mice I/R injury model and verified the effect of EIP-22 by measuring cardiac function, evaluating heart pathology and detecting serum LDH, CK-MB and cTnI level. Finally, the main signalling pathway was analysed by RNA-seq. In vitro, EIP-22 treatment significantly improved cells viabilities and MMP and attenuated the LDH, ROS and apoptosis level. In vivo, EIP-22 distinctly improved cardiac function, ameliorated myocardial infarction area and fibrosis and decreased serum LDH, CK-MB and cTnI level. Mechanistically, JAK/STAT signalling pathway was focussed by RNA-seq and we confirmed that EIP-22 up-regulated the expression of p-JAK2 and p-STAT3. Moreover, AG490, a selective inhibitor of JAK2/STAT3, eliminated the protective roles of EIP-22. The results uncovered that exercise-induced peptide EIP-22 protected cardiomyocytes from myocardial I/R injury via activating JAK2/STAT3 signalling pathway and might be a new candidate molecule for the treatment of myocardial I/R injury.
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http://dx.doi.org/10.1111/jcmm.16441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034444PMC
April 2021

Bmi-1 alleviates adventitial fibroblast senescence by eliminating ROS in pulmonary hypertension.

BMC Pulm Med 2021 Mar 5;21(1):80. Epub 2021 Mar 5.

Department of Forensic Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, People's Republic of China.

Objectives: Pulmonary hypertension (PH) is a life-threatening progressive disease with high mortality in the elderly. However, the pathogenesis of PH has not been fully understood and there is no effective therapy to reverse the disease process. This study aims to determine whether cellular senescence is involved in the development of PH.

Methods: The rat PH model was established by intraperitoneal injection of monocrotaline and evaluated by pulmonary arteriole wall thickness and right ventricular hypertrophy index. Human lung fibroblasts (HLFs) were treated with CoCl or hypoxia to induce cellular senescence in vitro. SA-β-gal staining and the changes of senescent markers were used to examine cellular senescence. The molecular mechanism of cellular senescence was further explored by detecting reactive oxygen species (ROS) levels and culturing cells with a conditioned medium.

Results: We revealed the cellular senescence of pulmonary adventitial fibroblasts in vivo in the rat PH model. The expression of Bmi-1, an important regulator of senescence, was decreased in the lungs of PH rats and localized in adventitial fibroblasts. The in vitro experiments showed that p16 expression was increased while Bmi-1 expression was decreased after CoCl treatment in HLFs. Mechanistically, Bmi-1 could alleviate CoCl-induced HLFs senescence by eliminating ROS which further promoted the proliferation of pulmonary artery smooth muscle cells by paracrine mode of action of HLFs.

Conclusion: Bmi-1 alleviates the cellular senescence of pulmonary fibroblasts in PH, which expands the pathogenesis of PH and provides a theoretical basis for targeting senescent cells in the treatment of PH.
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http://dx.doi.org/10.1186/s12890-021-01439-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934412PMC
March 2021

Peptidomics analysis revealed that a novel peptide VMP‑19 protects against Ang II‑induced injury in human umbilical vein endothelial cells.

Mol Med Rep 2021 04 2;23(4). Epub 2021 Mar 2.

Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

Vascular endothelial dysfunction is a vital pathological change in hypertension, which is mainly caused by apoptosis and oxidative stress injury of vascular endothelial cells. Peptidomics is a method for the direct analysis of small bioactive peptides in various biological samples using liquid chromatography‑mass spectrometry (MS)/MS. Given the advantages of the low molecular weight, optimum targeting and easy access to cells, peptides have attracted extensive attention in the field of drug research. However, to the best of our knowledge, little is currently known regarding the role of peptides in vascular endothelial injury. In order to investigate the peptides involved in vascular endothelial protection, MS was used to analyze the peptide profiles in the supernatant of human umbilical vein endothelial cells (HUVECs) stimulated by Ang II. The results revealed that 211 peptides were identified, of which six were upregulated and 13 were downregulated when compared with the control group. Subsequently, the present study analyzed the physical and chemical properties and biological functions of identified peptides by bioinformatics, and successfully screened a peptide (LLQDSVDFSLADAINTEFK) named VMP‑19 that could alleviate the apoptosis and oxidative stress injury of HUVECs induced by Ang II. In conclusion, to the best of our knowledge, the present study was the first to use peptidomics to analyze the peptide profiles of supernatant secreted by HUVECs, and revealed that the novel peptide VMP‑19 could protect HUVECs from apoptosis and oxidative stress injury. The results of the present study could provide novel insights into treatment strategies for hypertension.
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http://dx.doi.org/10.3892/mmr.2021.11937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930926PMC
April 2021

Peptide Szeto‑Schiller 31 ameliorates doxorubicin‑induced cardiotoxicity by inhibiting the activation of the p38 MAPK signaling pathway.

Int J Mol Med 2021 04 2;47(4). Epub 2021 Mar 2.

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

Oxidative stress serves a key role in doxorubicin (DOX)‑induced cardiotoxicity. The peptide Szeto‑Schiller (SS)31 is an efficacious antioxidant with the capacity to reduce mitochondrial reactive oxygen species (ROS) levels and scavenge free radicals. Although SS31 is involved in the pathophysiological process of various cardiovascular diseases, the role of SS31 in DOX‑induced cardiotoxicity remains unclear. To explore the effects of SS31 in DOX‑induced cardiotoxicity, the present study first constructed DOX‑induced cardiotoxicity models, in which H9c2 cells were incubated with 1 µM DOX for 24 h and C57BL/6 mice were administered DOX (20 mg/kg cumulative dose). The results of various assays in these models demonstrated that SS31 exhibited a cardioprotective effect and by attenuating the level of ROS, stabilizing the mitochondrial membrane potential and ameliorating myocardial apoptosis as well as fibrosis following treatment with DOX. Mechanistically, the results of the present study revealed that the p38 MAPK signaling pathway was inhibited by SS31 in DOX‑treated H9c2 cells, which was associated with the cardioprotective function of SS31. In addition, P79350, a selective agonist of p38 MAPK, reversed the protective effects of SS31. Taken together, these results demonstrated the effects of SS31 on ameliorating DOX‑induced cardiotoxicity and indicated its potential as a drug for the treatment of DOX‑induced cardiotoxicity.
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http://dx.doi.org/10.3892/ijmm.2021.4896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914074PMC
April 2021

Cytokeratin 19 fragment is associated with severity and poor prognosis of interstitial lung disease in anti-MDA5 antibody-positive dermatomyositis.

Rheumatology (Oxford) 2021 Jan 27. Epub 2021 Jan 27.

Department of Respiratory Medicine.

Objectives: In the present study, we aimed to assess the clinical significance of cytokeratin 19 fragment (CYFRA21-1) in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM-interstitial lung disease (MDA5-DM-ILD).

Methods: A total of 73 MDA5-DM-ILD patients were retrospectively analysed in this work. Their clinical characteristics, including clinical manifestations, laboratory findings, peripheral blood lymphocyte subsets and lung function, were compared between patients with acute/subacute interstitial pneumonia (A/SIP) and chronic interstitial pneumonia (CIP). The level of serum CYFRA21-1 was also compared between the above-mentioned two groups of patients, and its association with the clinical features and mortality of MDA5-DM-ILD was also evaluated.

Results: Of the 73 MDA5-DM-ILD patients, 26 patients exhibited the A/SIP pattern. The level of serum CYFRA21-1 was higher in MDA5-DM patients with A/SIP compared with the CIP group (P = 0.009). Lower oxygenation index (OI), CD3+CD4+ T cell counts and percentage of CD3+CD4+ cells were also observed in MDA5-DM patients with A/SIP compared with the CIP group. Higher serum CYFRA21-1, lower OI, and lower zone consolidation were associated with a higher risk of A/SIP in MDA5-DM-ILD. In addition, 38 decedents with MDA5-DM-ILD exhibited a greater level of CYFRA21-1 compared with 35 survivors (P < 0.001). Furthermore, it was a prognostic factor and also associated with a higher mortality rate (log-rank test, P < 0.001).

Conclusions: CYFRA21-1 could be a useful serum indicator associated with occurrence of A/SIP in MDA5-DM-ILD. Moreover, it was associated with a poor survival in MDA5-DM-ILD patients.
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http://dx.doi.org/10.1093/rheumatology/keaa843DOI Listing
January 2021

YTHDF1 Regulates Pulmonary Hypertension through Translational Control of MAGED1.

Am J Respir Crit Care Med 2021 05;203(9):1158-1172

Department of Forensic Medicine.

Posttranscriptional modifications are implicated in vascular remodeling of pulmonary hypertension (PH). mA (N-methyladenosine) is an abundant RNA modification that is involved in various biological processes. Whether mA RNA modification and mA effector proteins play a role in pulmonary vascular remodeling and PH has not been demonstrated. To determine whether mA modification and mA effectors contribute to the pathogenesis of PH. mA modification and YTHDF1 expression were measured in human and experimental PH samples. RNA immunoprecipitation analysis and mA sequencing were employed to screen mA-marked transcripts. Genetic approaches were employed to assess the respective roles of and in PH. Primary cell isolation and cultivation were used for function analysis of pulmonary artery smooth muscle cells (PASMCs). Elevated mA levels and increased YTHDF1 protein expression were found in human and rodent PH samples as well as in hypoxic PASMCs. The deletion of ameliorated PASMC proliferation, phenotype switch, and PH development both and . mA RNA immunoprecipitation analysis identified as an mA-regulated gene in PH, and genetic ablation of MAGED1 improved vascular remodeling and hemodynamic parameters in SU5416/hypoxia mice. YTHDF1 recognized and promoted translation of in an mA-dependent manner that was absent in -deficient PASMCs. In addition, silencing inhibited hypoxia-induced proliferation of PASMCs through downregulating PCNA. YTHDF1 promotes PASMC proliferation and PH by enhancing MAGED1 translation. This study identifies the mA RNA modification as a novel mediator of pathological changes in PASMCs and PH.
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http://dx.doi.org/10.1164/rccm.202009-3419OCDOI Listing
May 2021

The complete mitochondrial genome of Marsh Sandpiper (Charadriiformes, Scolopacidae).

Mitochondrial DNA B Resour 2020 Jul 11;5(3):2740-2741. Epub 2020 Jul 11.

College of Life Sciences, Jiangsu Key Laboratory for Biodiversity and Biotechnology, Nanjing Normal University, Nanjing, China.

The complete mitochondrial genome of Marsh Sandpiper was sequenced in this study. The circular mitogenome was 16,799 bp in length, which contained 13 protein-coding genes, two ribosomal RNAs (12S rRNA and 16S rRNA), 22 transfer RNA genes, and a D-loop region. The overall nucleotide composition was A: 31.51%, T: 25.45%, C: 29.51%, and G: 13.53%. Twenty-eight genes were encoded on the heavy strand, and the remaining nine genes were encoded on the light strand. The common start codon was ATG, and four stop codons and an incomplete stop codon (T-) were used in PCGs. This study improves our understanding of the mitogenomic characteristics and its phylogenetic relationships within Charadriiformes.
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http://dx.doi.org/10.1080/23802359.2020.1787895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782464PMC
July 2020

The complete mitochondrial genome of grey plover (Charadriiformes, charadriidae).

Mitochondrial DNA B Resour 2020 Jul 11;5(3):2738-2739. Epub 2020 Jul 11.

Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Jiangsu, Nanjing, China.

The complete mitochondrial genome of grey plover was obtained by next-generation sequencing. The circular genome was 16,860 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a control region. The overall nucleotide composition was A: 30.9%, T: 23.4%, C: 31.6%, G: 14.1%. Nine genes were encoded on the light strand, and the remaining 28 genes were encoded on the heavy strand. Most of the PCGs began with the ATG as the start codon, and four kinds of termination codons were used in this mitogenome. This study improves our understanding of the mitogenomic characteristics and its phylogenetic relationships within Charadriiformes.
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http://dx.doi.org/10.1080/23802359.2020.1787892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782006PMC
July 2020

Self-Activatable Photo-Extracellular Vesicle for Synergistic Trimodal Anticancer Therapy.

Adv Mater 2021 Feb 12;33(7):e2005562. Epub 2021 Jan 12.

School of Life Science, Beijing Institute of Technology, Beijing, 100081, P. R. China.

Extracellular vesicles (EVs) hold great potential in both disease treatment and drug delivery. However, accurate drug release from EVs, as well as the spontaneous treatment effect cooperation of EVs and drugs at target tissues, is still challenging. Here, an engineered self-activatable photo-EV for synergistic trimodal anticancer therapy is reported. M1 macrophage-derived EVs (M1 EVs) are simultaneously loaded with bis[2,4,5-trichloro-6-(pentyloxycarbonyl) phenyl] oxalate (CPPO), chlorin e6 (Ce6), and prodrug aldoxorubicin (Dox-EMCH). After administration, the as-prepared system actively targets tumor cells because of the tumor-homing capability of M1 EVs, wherein M1 EVs repolarize M2 to M1 macrophages, which not only display immunotherapy effects but also produce H O . The reaction between H O and CPPO generates chemical energy that activates Ce6, creating both chemiluminescence for imaging and singlet oxygen ( O ) for photodynamic therapy (PDT). Meanwhile, O -induced membrane rupture leads to the release of Dox-EMCH, which is then activated and penetrates the deep hypoxic areas of tumors. The synergism of immunotherapy, PDT, and chemotherapy results in potent anticancer efficacy, showing great promise to fight cancers.
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http://dx.doi.org/10.1002/adma.202005562DOI Listing
February 2021

A radiomics nomogram for the prediction of overall survival in patients with hepatocellular carcinoma after hepatectomy.

Cancer Imaging 2020 Nov 16;20(1):82. Epub 2020 Nov 16.

Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Army Medical University, No. 183 Xinqiao High Street, Shapingba District, Chongqing, 400037, China.

Background: Hepatocellular carcinoma (HCC) is associated with a dismal prognosis, and prediction of the prognosis of HCC can assist in therapeutic decision-makings. An increasing number of studies have shown that the texture parameters of images can reflect the heterogeneity of tumors, and may have the potential to predict the prognosis of patients with HCC after surgical resection. The aim of this study was to investigate the prognostic value of computed tomography (CT) texture parameters in patients with HCC after hepatectomy and to develop a radiomics nomogram by combining clinicopathological factors and the radiomics signature.

Methods: In all, 544 eligible patients were enrolled in this retrospective study and were randomly divided into the training cohort (n = 381) and the validation cohort (n = 163). The tumor regions of interest (ROIs) were delineated, and the corresponding texture parameters were extracted. The texture parameters were selected by using the least absolute shrinkage and selection operator (LASSO) Cox model in the training cohort, and a radiomics signature was established. Then, the radiomics signature was further validated as an independent risk factor for overall survival (OS). The radiomics nomogram was established based on the Cox regression model. The concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to evaluate the performance of the radiomics nomogram.

Results: The radiomics signature was formulated based on 7 OS-related texture parameters, which were selected in the training cohort. In addition, the radiomics nomogram was developed based on the following five variables: α-fetoprotein (AFP), platelet-to-lymphocyte ratio (PLR), largest tumor size, microvascular invasion (MVI) and radiomics score (Rad-score). The nomogram displayed good accuracy in predicting OS (C-index = 0.747) in the training cohort and was confirmed in the validation cohort (C-index = 0.777). The calibration plots also showed excellent agreement between the actual and predicted survival probabilities. The DCA indicated that the radiomics nomogram showed better clinical utility than the clinicopathologic nomogram.

Conclusion: The radiomics signature is a potential prognostic biomarker of HCC after hepatectomy. The radiomics nomogram that integrated the radiomics signature can provide a more accurate estimation of OS than the clinicopathologic nomogram for HCC patients after hepatectomy.
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http://dx.doi.org/10.1186/s40644-020-00360-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667801PMC
November 2020

Peptidomics Analysis Reveals Peptide PDCryab1 Inhibits Doxorubicin-Induced Cardiotoxicity.

Oxid Med Cell Longev 2020 13;2020:7182428. Epub 2020 Oct 13.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Doxorubicin (DOX) is limited due to dose-dependent cardiotoxicity. Peptidomics is an emerging field of proteomics that has attracted much attention because it can be used to study the composition and content of endogenous peptides in various organisms. Endogenous peptides participate in various biological processes and are important sources of candidates for drug development. To explore peptide changes related to DOX-induced cardiotoxicity and to find peptides with cardioprotective function, we compared the expression profiles of peptides in the hearts of DOX-treated and control mice by mass spectrometry. The results showed that 236 differential peptides were identified upon DOX treatment, of which 22 were upregulated and 214 were downregulated. Next, we predicted that 31 peptides may have cardioprotective function by conducting bioinformatics analysis on the domains of each precursor protein, the predicted score of peptide biological activity, and the correlation of each peptide with cardiac events. Finally, we verified that a peptide (SPFYLRPPSF) from Cryab can inhibit cardiomyocyte apoptosis, reduce the production of reactive oxygen species, improve cardiac function, and ameliorate myocardial fibrosis in vitro and vivo. In conclusion, our results showed that the expression profiles of peptides in cardiac tissue change significantly upon DOX treatment and that these differentially expressed peptides have potential cardioprotective functions. Our study suggests a new direction for the treatment of DOX-induced cardiotoxicity.
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http://dx.doi.org/10.1155/2020/7182428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582065PMC
May 2021

Swietenine extracted from Swietenia relieves myocardial hypertrophy induced by isoprenaline in mice.

Environ Toxicol 2020 Dec 20;35(12):1343-1351. Epub 2020 Jul 20.

Department of Forensic Sciences, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu, China.

As a traditional plant medicine in tropical areas, Swietenia macrophylla seeds are usually applied for some chronic diseases, including hypertension, diabetes, and so on. Few studies have been carried out to identify the effective elements in seed extract and their indications. In this study, we first investigated the functions of the swietenine, an extract from S. macrophylla seeds, using a model of myocardial hypertrophy induced by isoprenaline (ISO). At cellular level, H9c2 cell hypertrophy was also established through the treatment with ISO. The cardiac pathological remodeling was evaluated by echocardiography and histological analysis. Western blot and RT-qPCR were used to detect the expression of possible hypertrophy-promoting genes. Here, our results indicated that swietenine remarkably attenuated ISO-induced myocardial hypertrophy in vivo and in vitro. Moreover, Akt phosphorylation, ANP and BNP mRNA expression were efficiently decreased. Based on these findings, we concluded that swietenine might be a promising anti-hypertrophic agent against cardiac hypertrophy.
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http://dx.doi.org/10.1002/tox.22999DOI Listing
December 2020

Identification of Serum-Based Metabolic Feature and Characteristic Metabolites in Paraquat Intoxicated Mouse Models.

Front Physiol 2020 6;11:65. Epub 2020 Feb 6.

Department of Forensic Medicine, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.

Paraquat (PQ) is a widely used herbicide which can cause high mortality to humans. However, relatively few studies focus on metabolic feature of PQ intoxication for investigating the underlying mechanisms. Here we performed non-targeted metabolomics profiling of serum samples from acute and chronic PQ intoxicated mouse models by gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) to identify metabolic feature and characteristic metabolites of acute and chronic PQ intoxication. Results showed that 3-indolepropionic acid (IPA) and pathway of glycine, serine, and threonine metabolism were significantly altered after acute PQ intoxication; 2-hydroxybutyric acid and the ratio of L-serine/glycine were of significance between acute and chronic PQ intoxication. Then targeted metabolomics profiling was conducted by liquid chromatography-mass spectrometry (LC-MS) analysis to confirm the changes of IPA after acute PQ intoxication. Moreover, IPA-producing gut bacteria in feces were quantified by qRT-PCR to explain the varied IPA serum concentration. and were significantly suppressed after acute PQ intoxication. The data suggested that PQ caused oxidative damage partially through suppression of anti-oxidative metabolite producing gut bacteria. In conclusion, we identified characteristic metabolites and pathway of acute and chronic PQ intoxication which could be potential biomarkers and therapeutic targets.
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http://dx.doi.org/10.3389/fphys.2020.00065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017841PMC
February 2020

Lung carcinoma with diffuse cystic lesions misdiagnosed as pulmonary langerhans cell histocytosis: a case report.

BMC Pulm Med 2020 Feb 4;20(1):30. Epub 2020 Feb 4.

Department of Respiratory and Critical Care Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu, People's Republic of China.

Background: Cystic airspace is an uncommon imaging manifestation involved in non-small lung cancer (NSCLC). Diffuse cystic lesion is even rarer as pulmonary manifestation of NSCLC. In the present study, we reported a rare case of NSCLC associated with progressive diffusion of cystic lesions misdiagnosed as Pulmonary langerhans cell histocytosis (PLCH), finally diagnosed by transbronchial cryobiopsy (TBCB).

Case Presentation: A 52-year-old woman was admitted to our hospital due to cough and dyspnea. High-resolution computed tomography (HRCT) presented diffuse cystic shadow mostly, concomitantly with nodular densities in bilateral lungs. A lung biopsy revealed poorly differentiated adenocarcinoma with vascular tumor emboli. The epidermal growth factor receptor (EGFR) mutation on exon 18 (G719X, G719) was detected by mutation test. The patient received treatment of tyrosine kinase inhibitor (afatinib).

Conclusions: Diffuse cystic lesion can be a rare manifestation of lung cancer. It was important to improve the recognition of diffuse cystic lung diseases to avoid misdiagnosis.
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http://dx.doi.org/10.1186/s12890-020-1066-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001302PMC
February 2020

Trichostatin A alleviated ovarian tissue damage caused by cigarette smoke exposure.

Reprod Toxicol 2020 04 24;93:89-98. Epub 2020 Jan 24.

Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, 110004, China; Medical Research Center of Shengjing Hospital, China Medical University, Shenyang, 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China. Electronic address:

Cigarette smoke (CS) has a negative impact on women's health and fertility. Studies have shown that histone deacetylases 1 and 2 (HDAC1/2) were involved in oocyte development. However, the roles of HDAC1/2 in ovarian toxicity caused by CS exposure and the therapeutic potential of trichostatin A (TSA, a HDAC inhibitor) for ovarian tissue damage have not been investigated. In this study, Female C57BL/6 mice were exposed to CS from six cigarettes mixed with indoor air for 120 min (one cigarette for 20 min) using a whole-body mainstream smoke exposure system twice daily for 30 days. TSA (0.6 mg/kg body weight) was injected intraperitoneally into mice in the Control + TSA group and CS + TSA group every two days for 30 days. We found that exposure to CS resulted in ovarian tissue damage and HDAC1/2 over-expression. TSA alleviated the structural changes of ovarian tissue induced by smoking and prevented the activation of HDAC1/2. Exposure to CS caused autophagy inhibition and pyroptosis activation. TSA treatment restored the expression of autophagy-associated proteins and decreased the levels of pyroptosis-related proteins induced by CS exposure. The TSA effect may be mediated by inhibition of HDAC1/2 involved in autophagy and pyroptosis process.
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http://dx.doi.org/10.1016/j.reprotox.2020.01.006DOI Listing
April 2020

Coordinating bioorthogonal reactions with two tumor-microenvironment-responsive nanovehicles for spatiotemporally controlled prodrug activation.

Chem Sci 2020 Jan 13;11(8):2155-2160. Epub 2020 Jan 13.

School of Life Science, Beijing Institute of Technology No. 5 South Zhong Guan Cun Street Beijing 100081 China

Precise activation of prodrugs in tumor tissues is critical to ensuring specific antitumor efficacy, meanwhile reducing the serious adverse effects. Here, a spatiotemporally controlled prodrug activation strategy was provided by integrating the inverse electron demand Diels-Alder (IEDDA) reaction with two tumor-microenvironment-responsive nanovehicles. The prodrug (Dox-TCO) and [4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanamine (Tz) were separately camouflaged into low pH and matrix metalloproteinase 2 (MMP-2) sensitive micellar nanoparticles. After systemic administration, only in the tumor tissues could both the nanovehicles dissociate responding to two special tumor microenvironments, with Dox-TCO and Tz released and then immediately triggering the prodrug activation through the IEDDA reaction. The hierarchically regulated and locally confined Dox liberation led to dramatically decreased side-effects that were much lower than those of the clinical Doxorubicin Hydrochloride Liposomal Injection (Doxil), while the antitumor therapeutic effect was potent.
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http://dx.doi.org/10.1039/c9sc05036aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150104PMC
January 2020

Molecularly Engineered Macrophage-Derived Exosomes with Inflammation Tropism and Intrinsic Heme Biosynthesis for Atherosclerosis Treatment.

Angew Chem Int Ed Engl 2020 03 23;59(10):4068-4074. Epub 2020 Jan 23.

School of Life Science, Beijing Institute of Technology, No. 5 South Zhong Guan Cun Street, Beijing, 100081, China.

Atherosclerosis (AS) is a major contributor to cardiovascular diseases worldwide, and alleviating inflammation is a promising strategy for AS treatment. Here, we report molecularly engineered M2 macrophage-derived exosomes (M2 Exo) with inflammation-tropism and anti-inflammatory capabilities for AS imaging and therapy. M2 Exo are derived from M2 macrophages and further electroporated with FDA-approved hexyl 5-aminolevulinate hydrochloride (HAL). After systematic administration, the engineered M2 Exo exhibit excellent inflammation-tropism and anti-inflammation effects via the surface-bonded chemokine receptors and the anti-inflammatory cytokines released from the anti-inflammatory M2 macrophages. Moreover, the encapsulated HAL can undergo intrinsic biosynthesis and metabolism of heme to generate anti-inflammatory carbon monoxide and bilirubin, which further enhance the anti-inflammation effects and finally alleviate AS. Meanwhile, the intermediate protoporphyrin IX (PpIX) of the heme biosynthesis pathway permits the fluorescence imaging and tracking of AS.
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http://dx.doi.org/10.1002/anie.201913700DOI Listing
March 2020

Muscle death participates in myofibrillar abnormalities in FHL1 knockout mice.

Biochem Biophys Res Commun 2020 02 10;523(1):105-111. Epub 2019 Dec 10.

Medical Research Center of Shengjing Hospital, China Medical University, Shenyang, 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China. Electronic address:

Background: Mutations in the four and-a-half LIM domain protein 1 (FHL1) gene or FHL1 protein deletion have been identified as the cause of rare hereditary myopathies or cardiomyopathies. In our previous study, autophagy activation was associated with myofibrillar abnormalities in FHL1 knockout (KO) mice. P2RX7 induces cell death, such as autophagy, pyroptosis or apoptosis via cell-specific downstream signaling; however, the roles of P2RX7 in pyroptosis or apoptosis in myofibrillar abnormalities in FHL1 KO mice have not been well elucidated.

Methods: In this study, skeletal muscle and heart of 2.5 months old WT and FHL1 KO male mice histomorphology were examined by hematoxylin and eosin staining. The indicators for pyroptosis (NLRP3; ASC; cleaved-caspase1; IL-1β), apoptosis (Apaf-1; Bcl-2; caspase9; cleaved-caspase3), and P2RX7 were detected in the triceps (Tri), tibialis anterior muscles (TA), and heart by western blot and/or immunohistochemistry in WT and FHL1 KO male mice.

Results: Indicators for pyroptosis (ASC; cleaved-caspase1; IL-1β) and apoptosis (Apaf-1 and cleaved-caspase3), as well as P2RX7 were upregulated in Tri, tibialis TA, and heart in FHL1 KO mice, indicating pyroptosis and apoptosis play important roles in myofibrillar abnormalities in FHL1 KO mice.

Conclusions: P2RX7 may participate in myofibrillar abnormalities by activating pyroptosis and apoptosis in FHL1 KO mice. These findings have basic implications for the understanding of myopathies induced by FHL1 deficiency and provide new avenues for the treatment of these hereditary myopathies by modulating P2RX7.
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http://dx.doi.org/10.1016/j.bbrc.2019.12.026DOI Listing
February 2020

Responsive Exosome Nano-bioconjugates for Synergistic Cancer Therapy.

Angew Chem Int Ed Engl 2020 01 18;59(5):2018-2022. Epub 2019 Dec 18.

School of Life Science, Beijing Institute of Technology, Beijing, 100081, P. R. China.

Exosomes hold great potential in therapeutic development. However, native exosomes usually induce insufficient effects in vivo and simply act as drug delivery vehicles. Herein, we synthesize responsive exosome nano-bioconjugates for cancer therapy. Azide-modified exosomes derived from M1 macrophages are conjugated with dibenzocyclooctyne-modified antibodies of CD47 and SIRPα (aCD47 and aSIRPα) through pH-sensitive linkers. After systemic administration, the nano-bioconjugates can actively target tumors through the specific recognition between aCD47 and CD47 on the tumor cell surface. In the acidic tumor microenvironment, the benzoic-imine bonds of the nano-bioconjugates are cleaved to release aSIRPα and aCD47 that can, respectively, block SIRPα on macrophages and CD47, leading to abolished "don't eat me" signaling and improved phagocytosis of macrophages. Meanwhile, the native M1 exosomes effectively reprogram the macrophages from pro-tumoral M2 to anti-tumoral M1.
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http://dx.doi.org/10.1002/anie.201912524DOI Listing
January 2020

LncRNA Blnc1 expression and its effect on renal fibrosis in diabetic nephropathy.

Am J Transl Res 2019 15;11(9):5664-5672. Epub 2019 Sep 15.

Department of General Practice, Tongren Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200336, China.

Background And Objectives: Diabetic nephropathy (DN) is one of the commonest microvascular complications of diabetes and has been the major cause of end-stage renal disease in many countries. It is of great clinical significance to further explore more efficacious therapeutic strategies for DN. This study aims to explore the effect of Blnc1 on renal fibrosis in diabetic nephropathy.

Methods: In this study, mRNA level of Blnc1 was examined by RT-PCR. HE staining and Masson staining were adopted to detect kidney damage and renal fibrosis. The renal fibrosis was evaluated by the levels of PTEN, fibronectin, collagen I and collagen IV with immunofluorescence assay and western blot analysis. Oxidative Stress and inflammatory response were detected by ELISA assay. At the same time, western blot was performed to detect the proteins related to NRF2/HO-1 and NF-κB pathways.

Results: Blnc1 has higher expression in serum of DN patients, STZ-induced DN model and HG-induced HK2 cells. Blnc1 interference significantly attenuated renal fibrosis, inflammation and oxidative stress via NRF2/HO-1 and NF-κB pathways.

Conclusion: Our present study suggested that Blnc1 can affect inflammation, oxidative stress and renal fibrosis by Nrf2/HO-1 and NF-κB pathways in DN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789252PMC
September 2019

Trichostatin A inhibits skeletal muscle atrophy induced by cigarette smoke exposure in mice.

Life Sci 2019 Oct 28;235:116800. Epub 2019 Aug 28.

Medical Research Center of Shengjing Hospital, China Medical University, Shenyang 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China. Electronic address:

Aims: It is well known that cigarette smoke (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD) accompanied by skeletal muscle atrophy. Histone deacetylases (HDACs) that remove acetyl groups from target proteins are necessary for the muscle atrophy associated with skeletal muscle disuse. However, the role of HDACs and trichostatin A (TSA), a HDAC inhibitor, in skeletal muscle atrophy caused by CS exposure remains poorly understood.

Main Methods: Female mice were exposed to CS twice daily for 40 days and TSA injected intraperitoneally into CS-exposed mice on alternate days. Skeletal muscles were weighed and gastrocnemius (Gas) muscle histomorphology examined by hematoxylin and eosin staining. Histone deacetylases 1 and 2 (HDAC1/2), and markers of ubiquitin degradation, muscle differentiation, apoptosis, pyroptosis, and the cytoskeletal proteins were assessed by western blot and immunohistochemistry in Gas.

Keyfindings: CS exposure decreased body and skeletal muscle weights and triggered an increase in the percentage of fiber with centralized nuclei in Gas. HDAC1/2 proteins were upregulated in the Gas of mice exposed to CS, while TSA effectively inhibited HDAC1/2 protein levels and attenuated the loss of body weight and skeletal muscle wet weight induced by CS exposure. Markers for ubiquitin degradation, muscle differentiation, cytoskeletal proteins, apoptosis and pyroptosis were all upregulated following CS exposure and effectively restored by TSA.

Significance: TSA may inhibit skeletal muscle atrophy and histomorphological alterations induced by CS exposure by downregulating markers of ubiquitin degradation, muscle fiber differentiation, cytoskeletal proteins, apoptosis and pyroptosis via HDAC1/2 inhibition.
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http://dx.doi.org/10.1016/j.lfs.2019.116800DOI Listing
October 2019

The complete mitochondrial genome of the Spotted Greenshank (Charadriiforemes: Charadriidae).

Mitochondrial DNA B Resour 2019 Jul 12;4(2):2353-2354. Epub 2019 Jul 12.

Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, People's Republic of China.

The complete mitochondrial DNA genome of the Endangered Spotted Greenshank, , was detected using phenol-chloroform extraction procedure and polymerase chain reaction method. It is a circular molecule of 16,935 bp in size, exhibits the typical structure of mitochondrial genomes of Charadriiformes, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region. Overall base composition of the complete mitochondrial DNA is A (31.7%), T (25.5%), C (29.5%), and G (13.3%), the percentage of A and T (57.2%) is higher than G and C. The phylogenetic relationships of 34 species were reconstructed using the maximum-likelihood and Bayesian inference, and unravel is close to .
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http://dx.doi.org/10.1080/23802359.2019.1629349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687452PMC
July 2019

The role of P2X7 receptor in prognosis and metastasis of colorectal cancer.

Adv Med Sci 2019 Sep 2;64(2):388-394. Epub 2019 Jul 2.

Key Laboratory of Research and Application of Animal Models for Environmental and Metabolic Diseases, Medical Research Center of Shengjing Hospital, China Medical University, Shenyang, Liaoning Province, PR China. Electronic address:

Purpose: Colorectal cancer (CRC) is one of the leading causes of cancer mortality in the world. P2X7 receptor (P2X7R), encoded by the P2rx7 gene, is a trimeric ion channel activated by extracellular Adenosine triphosphate and is widely expressed in various types of tissues and tumors to regulate inflammation, cell proliferation, or death. The discovery of new biomarkers and understanding the role of P2X7R in CRC are therefore critical to improving the prognosis and treatment of CRC.

Materials And Methods: P2X7R expression was analyzed in CRC tumor samples and normal colorectal tissues from 97 patients and various colon cancer cell lines. The correlation of tumor antigens, survival periods, and P2X7R expression were documented.

Results: P2X7R and P2X7R populations were observed in CRC patients. P2X7R patients had relatively shorter survival periods, higher levels of serum carcinoembryonic antigen, and greater numbers of advanced tumors. In addition, P2X7R expression had a significant up-regulation in metastatic CRC and metastatic CRC cell lines, which indicates that P2X7R expression is positively associated with metastasis.

Conclusions: P2X7R expression might be a potential biomarker for prognosis and metastasis of CRC.
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http://dx.doi.org/10.1016/j.advms.2019.05.002DOI Listing
September 2019

A long-term retrospective study of patients with biopsy-proven cryptogenic organizing pneumonia.

Chron Respir Dis 2019 Jan-Dec;16:1479973119853829

1 Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical School, Nanjing, Jiangsu, China    .

Cryptogenic organizing pneumonia (COP) is characterized by good response to corticosteroids, but frequent relapses after reduction or cessation of treatment are noted. The incidence, risk factors of relapse, and long-term outcomes of patients with COP remain undetermined. Patients with COP from September 2010 to December 2017 were enrolled. Hospital and office records were used as data sources. Clinical information, lab examinations, chest radiographs, treatment courses, and follow-up data were collected. Relapse group was defined as worsening of clinical manifestations in combination with progression of radiographic abnormalities in the absence of identified causes. Eighty-seven patients with COP were enrolled. Of them, 73 patients were treated with corticosteroids with relapse rate yielding 31.5% (23 of 73). Eleven patients were treated with macrolides and none of them relapsed. Fever was more common (65.2% vs. 32.0%, p = 0.004), C-reactive protein (CRP) was higher (31.5 ± 39.4 mg/L vs. 17.5 ± 32.2 mg/L, p = 0.038), and diffusion capacity for carbon monoxide (DLCO) % predicted was lower (45.9 ± 14.2% vs. 57.6 ± 18.5%, p = 0.050) in relapse group compared to nonrelapse group. Four patients who presented with organizing pneumonia (OP) as the first manifestation were ultimately diagnosed with OP secondary to autoimmune disease in follow-up. We showed relapse was common in COP patients treated with corticosteroids, but the prognosis was favorable. Fever, elevated CRP, and a reduced DLCO were related to relapse. As OP may not always be cryptogenic, a careful follow-up should be programmed to diagnose the underlying systemic disease.
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http://dx.doi.org/10.1177/1479973119853829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547176PMC
August 2020

Trichostatin A inhibits uterine histomorphology alterations induced by cigarette smoke exposure in mice.

Life Sci 2019 Jul 1;228:112-120. Epub 2019 May 1.

Medical Research Center of Shengjing Hospital, China Medical University, Shenyang 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China. Electronic address:

Aims: Cigarette smoking results in well-known negative reproductive consequences. However, the role of histone deacetylase 1 and 2 (HDAC1/2) in the structural changes of uterine tissues induced by cigarette smoke (CS) exposure and the therapeutic potential of trichostatin A (TSA), a HDAC inhibitor, have not been investigated.

Main Methods: Female mice were exposed to CS twice daily for 30 days and TSA was injected intraperitoneally into CS-exposed mice on alternate days in the TSA-treated group. Uteri in the estrus phase were weighed and uterine histomorphology and HDAC1 cell distribution were examined by HE and immunohistochemistry. Markers associated with macro-autophagy (Beclin-1), autophagic flux (increased LC3-II and a lack of p62 accumulation), autophagy inhibiting factor (mTOR, phosphorylated mTOR and its upstream IRS, phosphorylated IRS), HDAC1/2, FOXO1 and FOXO3 were assessed by Western blot.

Key Findings: CS exposure decreased body weight and triggered uterine histomorphologic alterations, including a thinner myometrium and a reduced number of glandular and interstitial cells. HDAC1/2 were activated in uterine tissues after CS exposure and TSA effectively inhibited HDAC1/2 activation and attenuated the loss of body weight and uterine wet weight induced by CS exposure. TSA effectively restored the thickness of the myometrium and number of glandular and interstitial cells. TSA also restored the expression of markers of macro-autophagy (LC3-II and Beclin-1) and reduced phosphorylated mTOR, phosphorylated IRS, FOXO1 and FOXO3 activation.

Significance: TSA inhibited uterine histomorphologic alterations induced by CS exposure. The TSA effect might be associated with resumption of macro-autophagy via HDAC1/2 inhibition.
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http://dx.doi.org/10.1016/j.lfs.2019.04.069DOI Listing
July 2019

Pseudophosphatase STYX promotes tumor growth and metastasis by inhibiting FBXW7 function in colorectal cancer.

Cancer Lett 2019 07 11;454:53-65. Epub 2019 Apr 11.

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address:

Serine/threonine/tyrosine interacting protein (STYX), a member of protein tyrosine phosphatases, has recently been reported as a potential oncogene. However, the role of STYX in colorectal cancer (CRC) remains unknown. In this study, we found that STYX was highly expressed in CRC tissues and closely correlated with tumor development and survival of CRC patients. In vitro studies showed that overexpression of STYX promoted proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and inhibited apoptosis in CRC cells, while STYX knockdown had the opposite effects. Consistently, in vivo experiments showed that overexpression of STYX promoted tumor growth and lung metastasis. Mechanically, STYX bound to the F-box and WD repeat domain-containing7 (FBXW7) protein and inhibited its function. Co-regulation of STYX and FBXW7 expression reversed the biological changes mediated by regulation of STYX expression alone in CRC cells. Additionally, FBXW7 expression was negatively associated with STYX expression in CRC tissues, and low STYX levels accompanying high FBXW7 levels predicted favorable prognosis of CRC patients. In conclusion, our results suggest that STYX plays an oncogenic role by inhibiting FBXW7 and represents a potential therapeutic target and prognostic biomarker in CRC.
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http://dx.doi.org/10.1016/j.canlet.2019.04.014DOI Listing
July 2019
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