Publications by authors named "Xiao-Bo Yang"

89 Publications

miR-34c inhibits PDGF-BB-induced HAVSMCs phenotypic transformation and proliferation via PDGFR-β/SIRT1 pathway.

Mol Biol Rep 2021 Jun 10. Epub 2021 Jun 10.

Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, 25 Taiping Road, Luzhou, 646000, Sichuan, People's Republic of China.

The purpose of this study was to explore the effect of miR-34c on PDGF-BB-induced HAVSMCs phenotypic transformation and proliferation via PDGFR-β/SIRT1 pathway, so as to find a new method for early diagnosis and treatment of cardiovascular disease. HA-VSMCs were treated with platelet-derived growth factor-BB (PDGF-BB) at 0 h, 12 h, 24 h, 48 h or 36 h to explore the optimal time for phenotypic transformation of VSMCs. And then, PDGF-BB-induced HA-VSMCs were transfected with miR-34c mimics/mimics NC and pcDNA3.1-PDGFR-β/pcDNA3.1-NC to observe cell biological behaviour. CCK8 was used to detect cell proliferation activity. Transwell chamber assay was used to detect cell invasion. Early apoptosis was analyzed by flow cytometry. The expression of α-SMA and Smemb was detected by immunofluorescence staining. The expressions of PDGFR-β, IRF9, Acetyl-NF-κB/p65, Acetyl-p53 and CyclinD1 were analyzed by Western blot analysis. The expression of miR-34a, miR-34b and miR-34c was detected by RT-PCR, and the targeting relationship between miR-34c and PDGFR-β was detected by luciferase reporting assay. The results indicated the proliferation and migration of PDGF-BB-induced HA-VSMCs significantly increased, and apoptosis significantly decreased. Besides, α-SMA decreased significantly, while Smemb increased significantly. Furthermore, expressions of PDGFR-β, IRF9, Acetyl-NF-κB/p65, Acetyl-p53 and CyclinD1 increased significantly, and SIRT1 decreased significantly. Experimental results showed that, miR-34c mimics significantly inhibited cell proliferation and migration, and promoted cell apoptosis, and miR-34c inhibitor had the opposite effects. MiR-34c mimics significantly increased α-SMA expression and decreased Smemb expression, while the opposite effects were reflected after transfection with miR-34c inhibitor. Moreover, miR-34c mimics significantly decreased the expressions of PDGFR-β, IRF9, Acetyl-NF-κB/p65, Acetyl-p53 and CyclinD1, and significantly increased the expression of SIRT1, while miR-34c inhibitor had the opposite effects. Luciferase assay confirmed that PDGFR-β was a potential target of miR-34c. Subsequently, PDGF-BB-induced HA-VSMCs were co-transfected with miR-34c mimics and pcDNA3.1-PDGFR-β. The results indicated that PDGFR-β reversed the biological function of miR-34c mimic. The results revealed the potential application value of miR-34c as a marker molecule of phenotypic transformation, providing a potential target for improving phenotypic transformation.
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http://dx.doi.org/10.1007/s11033-021-06427-5DOI Listing
June 2021

Therapeutic effect of oxyberberine on obese non-alcoholic fatty liver disease rats.

Phytomedicine 2021 May 17;85:153550. Epub 2021 Mar 17.

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou 510120, PR China. Electronic address:

Background: Berberine (BBR) has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The metabolites of BBR were believed to contribute significantly to its pharmacological effects. Oxyberberine (OBB), a gut microbiota-mediated oxidative metabolite of BBR, has been firstly identified in our recent work.

Purpose: Here, we aimed to comparatively investigate the anti-NAFLD properties of OBB and BBR.

Methods: The anti-NAFLD effect was evaluated in high-fat diet-induced obese NAFLD rats with biochemical/ELISA tests and histological staining. The related gene and protein expressions were detected by qRT-PCR and Western blotting respectively. Molecular docking and dynamic simulation were also performed to provide further insight.

Results: Results indicated OBB remarkably and dose-dependently attenuated the clinical manifestations of NAFLD, which (100 mg/kg) achieved similar therapeutic effect to metformin (300 mg/kg) and was superior to BBR of the same dose. OBB significantly inhibited aberrant phosphorylation of IRS-1 and up-regulated the downstream protein expression and phosphorylation (PI3K, p-Akt/Akt and p-GSK-3β/GSK-3β) to improve hepatic insulin signal transduction. Meanwhile, OBB treatment remarkably alleviated inflammation via down-regulating the mRNA expression of MCP-1, Cd68, Nos2, Cd11c, while enhancing Arg1 mRNA expression in white adipose tissue. Moreover, OBB exhibited closer affinity with AMPK in silicon and superior hyperphosphorylation of AMPK in vivo, leading to increased ACC mRNA expression in liver and UCP-1 protein expression in adipose tissue.

Conclusion: Taken together, compared with BBR, OBB was more capable of maintaining lipid homeostasis between liver and WAT via attenuating hepatic insulin pathway and adipocyte inflammation, which was associated with its property of superior AMPK activator.
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http://dx.doi.org/10.1016/j.phymed.2021.153550DOI Listing
May 2021

LncRNA CYTOR affects the proliferation, cell cycle and apoptosis of hepatocellular carcinoma cells by regulating the miR-125b-5p/KIAA1522 axis.

Aging (Albany NY) 2020 12 9;13(2):2626-2639. Epub 2020 Dec 9.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

We aimed to investigate whether lncRNA CYTOR could sponge miR-125b-5p to affect hepatocellular carcinoma (HCC) cells through targeting KIAA1522. The expression of CYTOR, miR-125b-5p and KIAA1522 in HCC cells was detected by Real-time quantitative polymerase chain reaction (RT-qPCR) analysis. KIAA1522 expression in HCC tissues was detected by immunohistochemistry. The proliferation, cell cycle and apoptosis of HCC cells after transfection were respectively detected by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, and related protein expression was determined by Western blot analysis. As a result, The Cancer Genome Atlas (TCGA) database indicated that expression of CYTOR and KIAA1522 was increased in HCC tissues and high expression of CYTOR and KIAA1522 was related to worse overall survival. MiR-125b-5p expression was decreased in HCC tissues, which was negatively correlated with the expression of CYTOR and KIAA1522. The proliferation and cell cycle of HCC cells were suppressed by CYTOR interference while promoted by miR-125b-5p interference and KIAA1522 overexpression. The apoptosis of HCC cells was promoted by CYTOR interference while inhibited by miR-125b-5p interference and KIAA1522 overexpression. In conclusion, CYTOR interference suppressed the proliferation and cell cycle, and promoted the apoptosis of HCC cells by regulating the miR-125b-5p/KIAA1522 axis.
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http://dx.doi.org/10.18632/aging.202306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880333PMC
December 2020

Signature based on molecular subtypes of deoxyribonucleic acid methylation predicts overall survival in gastric cancer.

World J Gastroenterol 2020 Nov;26(41):6414-6430

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Background: Gastric cancer (GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early stages.

Aim: To identify the specific deoxyribonucleic acid (DNA) methylation sites that influence the prognosis of GC patients and explore the prognostic value of a model based on subtypes of DNA methylation.

Methods: Patients were randomly classified into training and test sets. Prognostic DNA methylation sites were identified by integrating DNA methylation profiles and clinical data from The Cancer Genome Atlas GC cohort. In the training set, unsupervised consensus clustering was performed to identify distinct subgroups based on methylation status. A risk score model was built based on Kaplan-Meier, least absolute shrinkage and selector operation, and multivariate Cox regression analyses. A test set was used to validate this model.

Results: Three subgroups based on DNA methylation profiles in the training set were identified using 1061 methylation sites that were significantly associated with survival. These methylation subtypes reflected differences in T, N, and M category, age, stage, and prognosis. Forty-one methylation sites were screened as specific hyper- or hypomethylation sites for each specific subgroup. Enrichment analysis revealed that they were mainly involved in pathways related to carcinogenesis, tumor growth, and progression. Finally, two methylation sites were chosen to generate a prognostic model. The high-risk group showed a markedly poor prognosis compared to the low-risk group in both the training [hazard ratio (HR) = 2.24, 95% confidence interval (CI): 1.28-3.92, < 0.001] and test (HR = 2.12, 95%CI: 1.19-3.78, = 0.002) datasets.

Conclusion: DNA methylation-based classification reflects the epigenetic heterogeneity of GC and may contribute to predicting prognosis and offer novel insights for individualized treatment of patients with GC.
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http://dx.doi.org/10.3748/wjg.v26.i41.6414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656213PMC
November 2020

Development and Verification of the Hypoxia-Related and Immune-Associated Prognosis Signature for Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2020 11;7:315-330. Epub 2020 Nov 11.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China.

Background: It has been widely suggested that the association of hypoxia with the immune status within the microenvironment of hepatocellular carcinoma (HCC) is of great clinical significance. The present work was carried out aiming to establish the hypoxia-related and immune-associated gene signature to stratify the risks in HCC.

Patients And Methods: The ssGSEA and t-SNE algorithms were utilized to estimate the immune and hypoxia statuses, respectively, using the TCGA database-derived cohort transcriptome profiles. Different immune groups are distinguished according to the ssGSEA scores, while the hypoxia-high and -low groups are inferred based on the distinct overall survival (OS) of the two groups of patients. Moreover, prognostic genes were identified using the Cox regression model in combination with the LASSO approach, which were later used to establish the hypoxia-related and immune-associated gene signature. At the same time, an ICGC cohort was used for external validation.

Results: A total of 13 genes, namely, and , were discovered by the LASSO approach for constructing a gene signature to stratify the risk of HCC. Those low-risk cases showed superior prognosis (OS) to the high-risk counterparts (p<0.05). Moreover, it was suggested by multivariate analysis that our constructed hypoxia-related and immune-associated prognosis signature might be used as the independent factor for prognosis prediction (p<0.001). Patients in high-risk groups had severe hypoxia, higher immune checkpoint expression such as PD-L1, and different immunocyte infiltration states (eg, higher infiltration of regulatory T cells in the high-risk group) compared with those low-risk patients.

Conclusion: Our as-constructed hypoxia-related and immune-associated prognosis signature can be used as an approach to stratify the risk of HCC.
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http://dx.doi.org/10.2147/JHC.S272109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667586PMC
November 2020

Molecular subtypes based on immune-related genes predict the prognosis for hepatocellular carcinoma patients.

Int Immunopharmacol 2021 Jan 7;90:107164. Epub 2020 Nov 7.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. Electronic address:

Background: Hepatocellular carcinoma (HCC) is a malignancy exhibiting the highest lethality. The present study aimed to identify different immune-related clusters in HCC and a robust tumor gene signature to facilitate the prognosis prediction for HCC patients.

Methods: For the 375 HCC cases collected from the dataset of Cancer Genome Atlas (TCGA), their overall survival (OS) and immune-related genes (IRGs) expression patterns were collected. Thereafter, consensus clustering was employed for grouping and functional enrichment, whereas the ESTIMATE algorithm and the CIBERSORT algorithm were used in subsequent assessment. Immunohistochemistry (IHC) was conducted to verify the protein expression of model genes in HCC and adjacent tissues.

Results: According to consensus clustering with 93-survival related IRGs, a total of five subgroups were found. These five clusters had different prognoses, immune statuses, and expression of immune checkpoints. Afterwards, 11 genes were enrolled for constructing the OS-related prediction model for TCGA HCC cases, which was then validated using the database of International Cancer Genome Consortium (ICGC). The protein expression of LCN2, S100A10, FABP6, PLXNA1, KITLG and OXTR were enhanced in HCC tissues relative to that in normal hepatic tissues, while the protein expression of S100A1, CCL26, CMTM4, IL1RN and RARG were reduced in HCC compared with normal tissues. In addition, different immunocyte infiltration levels between low- and high- groups were further examined.

Conclusions: According to our results, the IRGs-based classifications assist in explaining the HCC heterogeneity, which may help to develop the more efficient individualized treatments.
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http://dx.doi.org/10.1016/j.intimp.2020.107164DOI Listing
January 2021

Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China.

World J Gastroenterol 2020 Aug;26(30):4465-4478

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Background: Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma (aHCC). Several recent real-world studies appear to have confirmed this; however, there are etiological differences. This necessitates further real-world studies of lenvatinib across diverse populations, such as in China.

Aim: To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions.

Methods: This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy. Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Baseline characteristics and adverse events (AEs) were recorded throughout the entire study.

Results: In total, 54 HCC patients treated with lenvatinib monotherapy were included for final analysis. The objective response rate was 22% ( = 12) with a progression-free survival (PFS) of 168 d; however, AEs occurred in 92.8% of patients. Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage [hazard ratio (HR) 0.465; 95%CI: 0.23-0.93; = 0.031], portal vein tumor thrombus (HR 0.38; 95%CI: 0.15-0.94; = 0.037) and Child-Pugh classifications (HR 0.468; 95%CI: 0.22-0.97; = 0.042) were significant factors affecting PFS. The sensitivity (56.7%) and specificity (83.3%) of decreasing serum biomarkers including alpha-fetoprotein were calculated in order to predict tumor size reduction. Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib.

Conclusion: Our findings confirm previous evidence from the phase III REFLECT study. The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC. However, further analysis suggested that baseline characteristics, changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses. Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.
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http://dx.doi.org/10.3748/wjg.v26.i30.4465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438196PMC
August 2020

Construction of a lipid metabolism-related and immune-associated prognostic signature for hepatocellular carcinoma.

Cancer Med 2020 10 19;9(20):7646-7662. Epub 2020 Aug 19.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. We aimed to identify a robust lipid metabolism-related signature associated with the HCC microenvironment to improve the prognostic prediction of HCC patients.

Methods: We analyzed the gene expression profiles of lipid metabolism from Molecular Signatures Database and information of patients from The Cancer Genome Atlas. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and principal component analysis (PCA) were employed for functional annotation. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to verify the expression of model genes in HCC and adjacent tissues.

Results: As a result, a lipid metabolism-related signature consisting of acyl-CoA synthetase long-chain family member 6 (ACSL6), lysophosphatidylcholine acyltransferase 1, phospholipase A2 group 1B, lecithin-cholesterol acyltransferase (LCAT), and sphingomyelin phosphodiesterase 4 (SMPD4) was identified among HCC patients. Lysophosphatidylcholine acyltransferase 1, PLA2G1B, and SMPD4 were proved significantly high expression while ACSL6 and LCAT were remarkably low expression in our 15 pairs of matched HCC and normal tissues by qRT-PCR. Under different conditions, the overall survival (OS) of patients in low-risk group was prolonged than that in high-risk group. Moreover, the as-constructed signature was an independent factor, which was remarkably associated with gender, histologic grade, and platelet level of HCC patients. In addition, the receiver operating characteristic (ROC) curve analysis confirmed the good potency of the model. Functional enrichment analysis further revealed that lower fatty acid (FA) oxidation and higher infiltration of immunocytes were detected in patients from the high-risk group compared with those in the low-risk group.

Conclusions: Our findings indicate that the lipid metabolism-related signature shows prognostic significance for HCC.
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http://dx.doi.org/10.1002/cam4.3353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571839PMC
October 2020

[Preventing role of warmth-promotion needling in reducing intracellular Ca overload of in vitro hippocampal neuronal cells of vascular dementia rats].

Zhen Ci Yan Jiu 2020 Jun;45(6):454-60

Research Center of Gansu University of Traditional Chinese Medicine, Lanzhou 730000.

Objective: To investigate the underlying mechanisms of warming-promotion needling (WPN) for vascular dementia (VD) by observing its effect on the expression of L-type calcium channel current (Ica.L), changes of intracellular [Ca]i in neurons and pathomorphological changes of brain in VD rats.

Methods: One hundred and eight male SD rats were randomized into normal control, model, medication, WPN, uniform reinforcing-reducing needling (URRN), and needle-twirling groups (=18 in each group). The VD model was established by repeated occlusion and reperfusion of the bilateral common carotid arteries. Rats of the medication group were treated by gavage of Nimodipine twice a day for 14 days. For rats of the 3 acupuncture groups, WPN or URRN or needle-twirling was applied to "Dazhui" (GV14), "Baihui"(GV20) and "Shuigou"(GV26) for 30 min, once a day for 14 days. Changes of Ica.L in hippocampal neurons were observed by whole-cell patch clamp technique, and levels of [Ca]i in neuronal cells of living brain slice of hippocampal CA1 area were observed by laser confocal microscope. Histopathological changes of hippocampal CA1 area were observed under light microscope after H.E. stain.

Results: Compared with the normal control group, the current density of Ica.L, and the intracellular[Ca]i levels were significantly increased (<0.05), and the I-V curves of Ica.L was apparently shifted down in the model group. In comparison with the model group, the current density of Ica.L was obviously reduced (<0.05), the I-V curves of Ica.L shifted up and the intracellular Ca content notably decreased in the medication, WPN, URRN and needle-twirling groups (<0.05). The effect of WPN was significantly superior to those of URRN and needle-twiiling (<0.05). H.E. stain showed a reduction in the number of hippocampal neurons, dilation of intercellular space, swelling of cell body, karyopyknosis, disordered arrangement and increased number of gliacytes in the model group, which was apparently milder in the medication and 3 acupuncture groups (the WPN group in particular).

Conclusion: The WPN can reduce Ica.L current density and [Ca]i content of hippocampal neurons in brain slices of VD rats, which may contribute to its effect in relieving VD by suppressing calcium overload.
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http://dx.doi.org/10.13702/j.1000-0607.190191DOI Listing
June 2020

Construction of a new immune-related signature based on three lncRNAs as the factor for prognosis prediction of hepatocellular carcinoma.

Clin Transl Med 2020 Jun 11;10(2):e101. Epub 2020 Jun 11.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1002/ctm2.101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403822PMC
June 2020

Novel regulation of miR-34a-5p and HOTAIR by the combination of berberine and gefitinib  leading to inhibition of EMT in human lung cancer.

J Cell Mol Med 2020 05 5;24(10):5578-5592. Epub 2020 Apr 5.

Laboratory of Tumor Biology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.

HOTAIR is an important carcinogenic lncRNA and involves in tumorigenesis, and invasion. MiR-34a-5p functions as a tumour suppressor. However, the underlying mechanism of HOTAIR regulation especially in association with miR-34a-5p in non-small-cell lung cancer (NSCLC) has not been explored. Herein, we performed series of in vitro experiments, including viability, migration, invasion, apoptosis and in vivo xenograft model, and identified that HOTAIR was remarkably elevated in NSCLC cells. Enforced HOTAIR expression promoted migration and invasion, while depleted HOTAIR diminished the ability of migration and invasion of NSCLC cells. We also observed that miR-34a-5p was dramatically inhibited in NSCLC cells and the binding correlation between HOTAIR and miR-34a-5p was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. We also showed that induction of miR-34a-5p and reduction of HOTAIR, and the interaction between miR-34a-5p and HOTAIR resulted in the suppression of epithelial-mesenchymal transition (EMT) as illustrated by induction of key epithelial markers E-cadherin expression, reduction of vimentin and EMT-inducing transcription factor snail. Excessive expression of snail resisted miR-34a-5p-inhibited cell growth. Snail binds to E-cadherin promoter and regulates E-cadherin expression. There was a synergy in combination of berberine and gefinitib in this process. Similar findings were also observed in a tumour xenograft model. Collectively, this is the first report demonstrating reciprocal interaction of miR-34a-5p- and HOTAIR-mediated regulation of snail resulting in inhibition of EMT process by the combination of berberine and gefitinib suggesting that regulation of miR-34a-5p- and HOTAIR-mediated inhibition of EMT may provide novel treatment paradigms for lung cancer.
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http://dx.doi.org/10.1111/jcmm.15214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214156PMC
May 2020

Development of an immune-related prognostic index associated with hepatocellular carcinoma.

Aging (Albany NY) 2020 03 19;12(6):5010-5030. Epub 2020 Mar 19.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100010, China.

Liver hepatocellular carcinoma (LIHC), an inflammation-associated cancer induced by a variety of etiological factors, is still one of the most prevalent and lethal cancers in human population. In this study, the expression profiles of immune-related genes (IRGs) were integrated with the overall survival (OS) of 378 LIHC patients based on the Cancer Genome Atlas (TCGA) dataset. Moreover, the differentially expressed and survival related IRGs among LIHC patients were predicted through the computational difference algorithm and COX regression analysis. As a result, 7 genes, including HSPA4, S100A10, FABP6, CACYBP, HDAC1, FCGR2B and SHC1, were retrieved to construct a predictive model associated with the overall survival (OS) of LIHC patients. Typically, the as-constructed model performed moderately in predicting prognosis, which was also correlated with tumor grade. Functional enrichment analysis revealed that the genes of high-risk group were actively involved in mRNA binding and the spliceosome pathway. Intriguingly, the prognostic index established based on IRGs reflected infiltration by multiple types of immunocytes. Our findings screen several IRGs with clinical significance, reveal the drivers of immune repertoire, and illustrate the importance of a personalized, IRG-based immune signature in LIHC recognition, surveillance, and prognosis prediction.
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http://dx.doi.org/10.18632/aging.102926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138589PMC
March 2020

The roles of mutated SWI/SNF complexes in the initiation and development of hepatocellular carcinoma and its regulatory effect on the immune system: A review.

Cell Prolif 2020 Apr 11;53(4):e12791. Epub 2020 Mar 11.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Hepatocellular carcinoma (HCC) is a primary liver malignancy with a high global prevalence and a dismal prognosis. Studies are urgently needed to examine the molecular pathogenesis and biological characteristics of HCC. Chromatin remodelling, an integral component of the DNA damage response, protects against DNA damage-induced genome instability and tumorigenesis by triggering the signalling events that activate the interconnected DNA repair pathways. The SWI/SNF complexes are one of the most extensively investigated adenosine triphosphate-dependent chromatin remodelling complexes, and mutations in genes encoding SWI/SNF subunits are frequently observed in various human cancers, including HCC. The mutated SWI/SNF complex subunits exert dual functions by accelerating or inhibiting HCC initiation and progression. Furthermore, the abnormal SWI/SNF complexes influence the transcription of interferon-stimulated genes, as well as the differentiation, activation and recruitment of several immune cell types. In addition, they exhibit synergistic effects with immune checkpoint inhibitors in the treatment of diverse tumour types. Therefore, understanding the mutations and deficiencies of the SMI/SNF complexes, together with the associated functional mechanisms, may provide a novel strategy to treat HCC through targeting the related genes or modulating the tumour microenvironment.
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http://dx.doi.org/10.1111/cpr.12791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162795PMC
April 2020

Aberrant lipid metabolism in hepatocellular carcinoma cells as well as immune microenvironment: A review.

Cell Prolif 2020 Mar 31;53(3):e12772. Epub 2020 Jan 31.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high worldwide prevalence and poor prognosis. Researches are urgently needed on its molecular pathogenesis and biological characteristics. Metabolic reprogramming for adaptation to the tumour microenvironment (TME) has been recognized as a hallmark of cancer. Dysregulation of lipid metabolism especially fatty acid (FA) metabolism, which involved in the alternations of the expression and activity of lipid-metabolizing enzymes, is a hotspot in recent study, and it may be involved in HCC development and progression. Meanwhile, immune cells are also known as key players in the HCC microenvironment and show complicated crosstalk with cancer cells. Emerging evidence has shown that the functions of immune cells in TME are closely related to abnormal lipid metabolism. In this review, we summarize the recent findings of lipid metabolic reprogramming in TME and relate these findings to HCC progression. Our understanding of dysregulated lipid metabolism and associated signalling pathways may suggest a novel strategy to treat HCC by reprogramming cell lipid metabolism or modulating TME.
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http://dx.doi.org/10.1111/cpr.12772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106960PMC
March 2020

The Reciprocal Interaction Between LncRNA CCAT1 and miR-375-3p Contribute to the Downregulation of IRF5 Gene Expression by Solasonine in HepG2 Human Hepatocellular Carcinoma Cells.

Front Oncol 2019 18;9:1081. Epub 2019 Oct 18.

Laboratory of Tumor Biology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

Solasonine (SS), a natural glycoalkaloid component, has been shown to have potent inhibitory activity and cytotoxicity against many cancer types. However, the precise mechanisms underlying this, particularly in hepatocellular carcinoma (HCC) are poorly understood. In this study, we showed that SS inhibited growth of HCC cells. Mechanistically, we observed that SS increased the expression of miR-375-3p, whereas reducing levels of long non-coding RNAs (lncRNAs) CCAT1 was noticed in HepG2 HCC and other cells. In addition, we found that SS repressed transcription factors, SP1 and interferon regulatory factor 5 (IRF5), protein expressions. There was a reciprocal interaction among miR-375-3p, CCAT1, and SP1. Moreover, SS inhibited IRF5 promoter activity, which was not observed in cells transfected with excessive expressed SP1 vectors. Interestingly, exogenously expressed IRF5 was shown to reverse expressions of SS-inhibited CCAT1 and induced-miR-375-3p; and neutralized SS-inhibited growth of HCC cells. Similar results were also found mouse model. Collectively, our results show that SS inhibits HepG2 HCC growth through the reciprocal regulation between the miR-375-3p and lncRNA CCAT1, and this results in transcription factor SP1-mediated reduction of IRF5 expression. The regulations and interactions among miR-375-3p, CCAT1, SP1, and IRF5 axis unveil a novel molecular mechanism underlying the anti-HCC growth by SS. IRF5 may be a potential target for treatment of HCC.
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http://dx.doi.org/10.3389/fonc.2019.01081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813207PMC
October 2019

Trichostatin A modulates the macrophage phenotype by enhancing autophagy to reduce inflammation during polymicrobial sepsis.

Int Immunopharmacol 2019 Dec 31;77:105973. Epub 2019 Oct 31.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Sepsis is a syndrome of life-threatening organ dysfunction caused by dysregulated host responses to infection. Macrophage polarization is a key process involved in the pathogenesis of sepsis. Recent evidence has demonstrated that autophagy participates in the regulation of macrophage polarization in different phases of inflammation. Here, we investigated whether trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes the macrophage M2 phenotype by enhancing autophagy to counteract excessive inflammation in a cecal ligation and puncture (CLP) mouse model. TSA stimulation increased the proportions of M2 marker (CD206, CD124 and CD23)-labeled RAW264.7 macrophages. Furthermore, with increasing TSA doses, autophagy was enhanced gradually. Interestingly, the autophagy activator rapamycin (Rap), also known as an mTOR inhibitor, unexpectedly decreased the proportions of M2 marker-labeled macrophages. However, TSA treatment reversed the Rap-induced decreases in CD206-labeled macrophages. Next, we stimulated different groups of RAW264.7 cells with the autophagy inhibitors MHY1485 or 3-methyladenine (3-MA). Inhibition of autophagy at any stage in the process suppressed TSA-induced macrophage M2 polarization, but the effect was not associated with mTOR activity. In vivo, TSA administration promoted peritoneal macrophage M2 polarization, increased LC3 II expression, attenuated sepsis-induced organ (lung, liver and kidney) injury, and altered systemic inflammatory cytokine secretion. However, 3-MA abolished the protective effects of TSA in CLP mice and decreased the number of M2 peritoneal macrophages. Therefore, TSA promotes the macrophage M2 phenotype by enhancing autophagy to reduce systemic inflammation and ultimately improves the survival of mice with polymicrobial sepsis.
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http://dx.doi.org/10.1016/j.intimp.2019.105973DOI Listing
December 2019

[Warming-promotion needling improves learning-memory ability by up-regulating expression of hippocampal nicotinic acetylcholine receptor subunit in rats with vascular dementia].

Zhen Ci Yan Jiu 2019 Oct;44(10):709-14

Scientific Research and Experiment Center of Gansu University of Traditional Chinese Medicine, Lanzhou 730000.

Objective: To investigate the mechanism of Warming-promotion needling underlying improvement of vascular dementia (VD) by observing its effect on learning-memory ability and expression of hippocampal nicotinic acetylcholine receptor(nAChR)subunit proteins and mRNAs in rats with VD.

Methods: Sixty male SD rats were randomized into normal control, model, medication, warming-promotion needling(WPN), uniform reinforcing-reducing needling (URRN), and needle-twirling groups (=10 in each group). The VD model was established via repeated occlusion and reperfusion of the bilateral common carotid arteries. Rats of the medication group were fed with Nimodipine twice a day for 14 days. For rats of the 3 acupuncture groups, WPN, or URRN or needle-twirling was applied to"Dazhui"(GV14),"Baihui"(GV20) and"Shuigou"(GV26) for 30 min, once a day for 14 days. The learning-memory ability was detected by Morris water maze tests, and the expression levels of nAChR α4, α7 and β2 subunit proteins and mRNAs in the hippocampus were detected by Western blot and real-time PCR, separately.

Results: Compared with the normal group, the escape latency of Morris water maze tests was significantly prolonged (<0.05), and the number of the original safe-platform quadrant crossing was significantly reduced in the model group (<0.05). The expression levels of nAChR α4, α7, β2 subunit proteins and mRNAs (except β2 mRNA) in the hippocampus were significantly decreased in the model group relevant to the normal group (<0.05). Following the interventions, the increased escape latency, and the reduced safe-platform quadrant crossing times, and the down-regulated expression levels of hippocampal nAChR α4, α7, β2 subunit proteins and mRNAs in the medication, WPN, URRN and needle-twirling groups were all reversed (<0.05). The effects of WPN were significantly superior to those of URRN and needle-twirling in up-regulating nAChR α4, α7, β2 subunit proteins and mRNAs (<0.05).

Conclusion: The warming-promotion needling can improve the learning and memory ability in VD rats, which may be related to its effects in up-regulating the expression of nAChR su-bunits in the hippocampus.
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http://dx.doi.org/10.13702/j.1000-0607.190202DOI Listing
October 2019

Apoptosis induced by bruceine D in human non‑small‑cell lung cancer cells involves mitochondrial ROS‑mediated death signaling.

Int J Mol Med 2019 Dec 3;44(6):2015-2026. Epub 2019 Oct 3.

Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China.

Bruceine D is one of the active components of Brucea javanica (L.) Merr., which is widely used to treat cancer in China. The aim of the present study was to evaluate the potential effect of bruceine D against non‑small‑cell lung cancer (NSCLC) cells and delineate its underlying mechanisms. The results indicated that treatment with bruceine D markedly inhibited the proliferation of wild‑type NSCLC cells and epidermal growth factor receptor‑mutant cells in a dose‑ and time‑dependent manner, and significantly decreased the colony‑forming ability and migration of A549 cells. Hoechst 33342 staining and flow cytometric analysis demonstrated that treatment with bruceine D effectively induced apoptosis of A549 cells. In addition, the proapoptotic effect of bruceine D was found to be associated with G0‑G1 cell cycle arrest, accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde, depletion of glutathione levels and disruption of mitochondrial membrane potential. Additionally, pretreatment with N‑acetylcysteine, a ROS scavenger, significantly attenuated the bruceine D‑induced inhibition in A549 cells. Western blotting demonstrated that treatment with bruceine D significantly suppressed the expression of the anti‑apoptotic proteins Bcl‑2, Bcl‑xL and X‑linked inhibitor of apoptosis, enhanced the expression levels of apoptotic proteins Bax and Bak, and inhibited the expression of pro‑caspase‑3 and pro‑caspase‑8. Based on these results, it may be suggested that inhibition of A549 NSCLC cell proliferation by bruceine D is associated with the modulation of ROS‑mitochondrial‑mediated death signaling. This novel insight may provide further evidence to verify the anticancer efficacy of B. javanica, and support a role for bruceine D in the anti‑NSCLC treatment.
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http://dx.doi.org/10.3892/ijmm.2019.4363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844635PMC
December 2019

Liver graft rejection following immune checkpoint inhibitors treatment: a review.

Med Oncol 2019 Oct 11;36(11):94. Epub 2019 Oct 11.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Wangfujing, Beijing, 100730, China.

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a variety of solid tumors; nonetheless, they have not been well investigated and are still recognized as a relative contraindication for patients with a liver transplantation (LT) history, since ICIs treatment might potentially lead to graft rejection. The program death-1 (PD-1) and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways are implicated in the tolerance of transplanted organ, as well as blockade of the pathways, which contribute to eliminating tumors and may inadvertently lead to peripheral transplant rejection. Currently, no guidelines are available regarding the treatment for ICIs patients with a prior LT history. Therefore, this study was carried out to review the recent studies, attempting to introduce the ICIs-related graft rejection after LT from various aspects. We believed that ICIs could be given for the well-informed patients receiving LT and developed recurrence in a controlled setting. Typically, these patients should be treated according to a clinical care path or a prospective clinical trial, so as obtain a persistent anti-tumor immune response in the meantime of avoiding graft rejection, adjust the immunosuppression, reduce the possibility of graft loss following rejection, and have the opportunity to develop biomarkers for tumor response and transplant rejection.
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http://dx.doi.org/10.1007/s12032-019-1316-7DOI Listing
October 2019

Paraneoplastic leukemoid reaction in a patient with sarcomatoid hepatocellular carcinoma: A case report.

World J Clin Cases 2019 Jun;7(11):1330-1336

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Background: Sarcomatoid hepatocellular carcinoma (SHC) combined with paraneoplastic leukemoid reaction (PLR), which is associated with a poor prognosis, is rarely seen in the clinic. Here, we report the case of a patient in the above situation.

Case Summary: A 75-year-old female patient with a past medical history of hypertension and cerebral infarction paid a hospital visit as a result of right upper quadrant abdominal pain and anorexia for two months. Laboratory examination revealed a white blood cell (WBC) count of 43790/μL, which was then increased up to 77050/μL. In addition, the results of bone marrow examination suggested a leukemoid reaction. Computed tomography (CT) revealed a focal hepatic mass, which was confirmed through pathological examination to be an SHC postoperatively. In addition, the WBC count had fallen to a normal level before she left the hospital. However, the patient died two and a half months after the second hospital admission.

Conclusion: This is a rare case of SHC combined with PLR, both of which have an extremely poor prognosis.
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http://dx.doi.org/10.12998/wjcc.v7.i11.1330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580346PMC
June 2019

Comparison of anti-inflammatory effects of berberine, and its natural oxidative and reduced derivatives from Rhizoma Coptidis in vitro and in vivo.

Phytomedicine 2019 Jan 1;52:272-283. Epub 2018 Oct 1.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address:

Background: Berberine (BBR) is the most abundant and major active constituent of Rhizoma Coptidis (RC), which has been widely used to treat inflammatory diseases in traditional oriental medicine. Despite BBR has been found to exhibit pronounced anti-inflammatory effect, the anti-inflammatory activities of its natural derivatives were sparsely dissected out.

Purpose: To comparatively investigate the anti-inflammatory potential of BBR, and its natural oxoderivative (oxyberberine, OBB) and reduced derivative (dihydroberberine, DHBB) in vitro and in vivo, and delineate the possible underlying mechanism.

Methods: LC-MS/MS was used to identify the natural derivatives of BBR in RC. The potential anti-inflammatory properties of BBR and its natural derivatives were comparatively evaluated in vitro by lipopolysaccharide (LPS)-induced RAW264.7 macrophages cells, and in vivo via three typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by ELISA, qRT-PCR and Western blotting.

Results: LC-MS/MS led to the identification of BBR, OBB and DHBB in RC ethyl acetate extract. The in vitro assay indicated that BBR, OBB and DHBB (1.25, 2.5 and 5 μM) pretreatment significantly decreased the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandinE2 (PGE) and nitricoxide (NO), and inhibited the mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitricoxide synthase (iNOS) in a dose-dependent manner, with relative efficiency of OBB > BBR > DHBB. Furthermore, OBB, BBR and DHBB remarkably inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 and inhibitory kappa Bα (IκBα). In vivo, BBR (20 mg/kg) and OBB (5, 10, and 20 mg/kg) pretreatment significantly ameliorated the xylene-induced ear edema, carrageenan-stimulated paw edema, and acetic acid-elicited vascular permeability in mice in a dose-dependent manner, with OBB exhibiting superior anti-inflammatory effect at the same dose (20 mg/kg). Histopathological analysis indicated that OBB and BBR could markedly attenuate the inflammatory deterioration and decrease the cellular infiltration in paw tissues. Additionally, the carrageenan-induced increases in TNF-α, IL-6, IL-1β, PGE and NO productions, and COX-2 and iNOS mRNA expressions were effectually and concentration-dependently suppressed by OBB and BBR pretreatment.

Conclusion: The anti-inflammatory activity of BBR and its natural derivatives was in the order of OBB > BBR > DHBB. OBB was for the first time found to be endowed with pronounced anti-inflammatory property, which was probably associated with suppressing the activation of NF-κB signaling pathway, and the subsequent gene expressions and productions of pro-inflammatory mediators. The results might contribute to illuminating the pharmacodynamic underpinnings of RC and provide evidence for developing OBB as a safe and promising natural lead compound in inflammation treatment.
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http://dx.doi.org/10.1016/j.phymed.2018.09.228DOI Listing
January 2019

Anamorphic fractional Fourier transforms graded index lens designed using transformation optics.

Authors:
Xiao-Bo Yang Jin Hu

Opt Express 2018 Oct;26(21):27528-27544

An anamorphic fractional Fourier transform (AFrFT) lens based on graded index (GRIN) materials and designed with the help of transformation optics is proposed. Cross sections of the new lens are mapped from those of a standard quadratic GRIN lens via gradually varied conformal transformations. This lens can afford complicated anamorphic patterns in the fractional Fourier domain for any fractional order, possibly leading to many new applications. Three samples are shown, which offer higher distinguishability in the fractional Fourier domain, a more precisely recognized matched filter, and stronger security of the AFrFT-based optical encryption. With metamaterials development, including three-dimensional printing technologies, GRIN media fabrication has become more convenient; thus, the proposed lens may have vast application prospects in signal processing. The design also demonstrates the ability and flexibility of the transformation optics in exploring new Fourier optics devices.
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http://dx.doi.org/10.1364/OE.26.027528DOI Listing
October 2018

Repression of PDK1- and LncRNA HOTAIR-Mediated EZH2 Gene Expression Contributes to the Enhancement of Atractylenolide 1 and Erlotinib in the Inhibition of Human Lung Cancer Cells.

Cell Physiol Biochem 2018 17;49(4):1615-1632. Epub 2018 Sep 17.

Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.

Background/aims: We previously showed that the major bioactive compound of Atractylodes macrocephula Koidz atractylenolide 1 (ATL-1) inhibited human lung cancer cell growth by suppressing the gene expression of 3-Phosphoinositide dependent protein kinase-1 (PDK1 or PDPK1). However, the potentially associated molecules and downstream effectors of PDK1 underlying this inhibition, particularly the mechanism for enhancing the anti-tumor effects of epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs), remain unknown.

Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Western blot analyses were performed to examine the protein expressions of PDK1 and of zeste homolog 2 (EZH2). The levels of long non-coding RNA (lncRNA) and HOX transcript antisense RNA (HOTAIR) were examined via qRT-PCR. RNA-binding protein immunoprecipitation assays were used to analyze HOTAIR interaction with EZH2. The promoter activity of the EZH2 gene was determined using Secrete-Pair Dual Luminescence Assay Kit. Exogenous expressions of PDK1, HOTAIR, and EZH2 were conducted via transient transfection assays. A xenografted tumor model was used to further evaluate the effect of ATL-1 in the presence or absence of erlotinib in vivo.

Results: We showed that the combination of ATL-1 and EGFR-TKI erlotinib further inhibited growth and induced cell arrest of the human lung cancer cells, determined by both MTT and flow cytometry assays. ATL-1 inhibited the protein expression and the promoter activity of EZH2, which was reversed in cells with PDK1 overexpression. Interestingly, ATL-1 inhibited the expression levels of HOTAIR. While silencing HOTAIR inhibited the expressions of PDK1 and EZH2, overexpression of HOTAIR reduced the ATL-1-reduced PDK1 and EZH2 protein expressions and EZH2 promoter activity. In addition, ATL-1 reduced the HOTAIR binding to the EZH2 protein. Moreover, we found that exogenously expressed EZH2 antagonized the effect of ATL-1 on cell growth inhibition. Consistent with the in vitro results, ATL-1 inhibited tumor growth and the expression levels of HOTAIR, protein expressions of EZH2 and PDK1 in vivo. Importantly, there was synergy of the combination of ATL-1 and erlotinib in this process.

Conclusion: Here, we provide the first evidence that ATL-1 inhibits lung cancer cell growth through inhibiting not only the PDK1 but also the lncRNA HOTAIR, which results in the reduction of one downstream effector EZH2 expression. The novel interplay between the HOTAIR and EZH2, as well as repressions of the PDK1 and HOTAIR coordinate the overall effects of ATL-1. Importantly, the combination of ATL-1 and EGFR-TKI erlotinib exhibits synergy. Thus, targeting the PDK1- and HOTAIR-mediated downstream molecule EZH2 by the combination of ATL-1 and erlotinib potentially facilitates the development of an additional novel strategy to combat lung cancer.
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http://dx.doi.org/10.1159/000493497DOI Listing
October 2018

Prognostic significance of the fibrinogen-to-albumin ratio in gallbladder cancer patients.

World J Gastroenterol 2018 Aug;24(29):3281-3292

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Aim: To investigate the prognostic role of fibrinogen-to-albumin ratio (FAR) on patients with gallbladder cancer (GBC) in this study.

Methods: One hundred and fifty-four GBC patients were retrospectively analyzed, who received potentially curative cholecystectomy in our institute from March 2005 to December 2017. Receiver operating characteristic curve (ROC curve) was used to determine the optimal cut-offs for these biomarkers. In addition, Kaplan-Meier survival analysis as well as multivariate analysis were applied for prognostic analyses.

Results: ROC curve revealed that the optimal cut-off value for FAR was 0.08. FAR was significantly correlated with age ( = 0.045), jaundice ( < 0.001), differentiation ( = 0.002), resection margin status ( < 0.001), T stage ( < 0.001), TNM stage ( < 0.001), and CA199 ( < 0.001) as well as albumin levels ( < 0.001). Multivariate analysis indicated that the resection margin status [hazard ratio (HR): 2.343, 95% confidence interval (CI): 1.532-3.581, < 0.001], TNM stage ( = 0.035), albumin level (HR = 0.595, 95%CI: 0.385-0.921, = 0.020) and FAR (HR: 2.813, 95%CI: 1.765-4.484, P < 0.001) were independent prognostic factors in GBC patients.

Conclusion: An elevated preoperative FAR was significantly correlated with unfavorable overall survival in GBC patients, while an elevated preoperative albumin level was a protective prognostic factor for patients with GBC. The preoperative FAR could be used to predict the prognosis of GBC patients, which was easily accessible, cost-effective and noninvasive.
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http://dx.doi.org/10.3748/wjg.v24.i29.3281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079291PMC
August 2018

Efficacy and indication optimization of Chinese medicine (Tiao-Chang Ke-Min granules) for diarrhea-predominant irritable bowel syndrome: study protocol for a randomized controlled trial.

Trials 2018 Jul 11;19(1):367. Epub 2018 Jul 11.

Chinese Medicine Syndrome Research Team, Guangdong Provincial Hospital of Chinese Medicine, No. 111, DaDe Road, Guangzhou, 510120, China.

Background: Irritable bowel syndrome (IBS) is a chronic, recurring condition, prevalent in the general population. Current medication treatments usually leave patients undertreated. Nowadays, Chinese medicine (CM) is being considered as a promising treatment approach for IBS. However, due to methodological limitations, there is no strong evidence to support CM. Although IBS relapses are common, the relapse assessment has always been neglected in CM study designs. Meanwhile, in clinical practice and studies, it has been found that certain CM formulas can only benefit certain kinds of patients. Discovering what population and illness characteristics likely respond to outcomes may help improve the effectiveness of CM. The aims of this study are to evaluate the efficacy and safety of Tiao-Chang Ke-Min (TCKM) granules for IBS, especially in reducing IBS symptoms' relapse, by a high-quality randomized controlled trial and then to optimize the indication of the TCKM granules.

Methods/design: This is a parallel-group, randomized, double-blind, placebo-controlled trial embedded with outcome predictive factors. Eligible patients with diarrhea-predominant IBS will be randomized into either a TCKM granule group or a placebo group. Patients from both groups will receive health education. The treatment duration is 4 weeks and the follow-up is 12 weeks. The primary outcome is global improvement measured with adequate relief (AR). The second outcome measures include time until relief, time until first relapse, total relapse times, long-term effectiveness, individual symptoms, IBS-Symptom Severity Score (IBS-SSS), IBS-Quality of Life Questionnaire (IBS-QOL), and Hospital Anxiety and Depression Scale (HADS). Predictive factors associated with patient and illness characteristics have been widely collected. These factors will be embedded in this trial for further identification.

Discussion: This trial may provide high-quality evidence on the efficacy and safety of TCKM granules for IBS and a more accurate indication. Importantly, this trial will provide a new research method for improving the therapeutic effects of CM for clinicians and researchers. To address IBS relapse assessment, a series of special definitions of relapse incidents has been made for this trial.

Trial Registration: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17010600 . Registered on 9 February 2017.
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http://dx.doi.org/10.1186/s13063-018-2754-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042407PMC
July 2018

Prognostic impact of the red cell distribution width in esophageal cancer patients: A systematic review and meta-analysis.

World J Gastroenterol 2018 May;24(19):2120-2129

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Aim: To clarify the previous discrepant conclusions, we performed a meta-analysis to evaluate the prognostic value of red cell distribution width (RDW) in esophageal cancer (EC).

Methods: We searched the PubMed, EMBASE, Web of Science and Cochrane Library databases to identify clinical studies, followed by using STATA version 12.0 for statistical analysis. Studies that met the following criteria were considered eligible: (1) Studies including EC patients who underwent radical esophagectomy; (2) studies including patients with localized disease without distant metastasis; (3) studies including patients without preoperative neoadjuvant therapy; (4) studies including patients without previous antiinflammatory therapies and with available preoperative laboratory outcomes; (5) studies reporting association between the preoperative RDW and overall survival (OS)/disease-free survival (DFS)/cancer-specific survival (CSS); and (6) studies published in English.

Results: A total of six articles, published between 2015 and 2017, fulfilled the selection criteria in the end. Statistical analysis showed that RDW was not associated with the prognosis of EC patients, irrespective of OS/CSS [hazard ratio (HR) = 1.27, 95% confidence interval (CI): 0.97-1.57, = 0.000] or DFS (HR = 1.42, 95%CI: 0.96-1.88, = 0.000). Subgroup analysis indicated that elevated RDW was significantly associated with worse OS/CSS of EC patients when RDW > 13% (HR = 1.45, 95%CI: 1.13-1.76, = 0.000), when the patient number ≤ 400 (HR = 1.45, 95%CI: 1.13-1.76, = 0.000) and when the study type was retrospective (HR = 1.42, 95%CI : 1.16-1.69, = 0.000).

Conclusion: Contrary to our general understanding, this meta-analysis revealed that RDW cannot serve as an indicator of poor prognosis in patients with EC. However, it may still be a useful predictor of unfavorable prognosis using an appropriate cut-off value.
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http://dx.doi.org/10.3748/wjg.v24.i19.2120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960817PMC
May 2018

Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients.

World J Gastroenterol 2018 Apr;24(13):1451-1463

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Aim: To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma (GBC).

Methods: The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. Based on the HRs calculated multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0.

Results: ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival (OS) (HR = 1.711, 95%CI: 1.114-2.627, = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735 (for preoperative plasma fibrinogen only) and 0.729 (for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199 ( < 0.001), resection margin ( < 0.001) and TNM stage ( = 0.010) were independent prognostic factors for GBC.

Conclusion: The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.
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http://dx.doi.org/10.3748/wjg.v24.i13.1451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889825PMC
April 2018

WITHDRAWN: SIKE1 deficiency accelerates hepatic ischemia/reperfusion (IR) injury through enhancing Toll-like receptor-3-regulated inflammation.

Biochem Biophys Res Commun 2018 Jan 31. Epub 2018 Jan 31.

Department of Neonatology, The Central Hospital of Wuhan, Wuhan 430014, China.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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http://dx.doi.org/10.1016/j.bbrc.2018.01.125DOI Listing
January 2018

Manipulating and detecting the chirpiness of spatial chirp signals via fractional Fourier lenses designed by transformation optics.

Appl Opt 2017 Nov;56(32):9119-9125

Estimating the chirpiness of a spatial chirp signal is important in many optical engineering applications. With the help of transformation optics, a new kind of fractional Fourier transform lens is designed by deforming the conventional graded index lens through conformal mapping, which can manipulate the chirpiness of the input chirp signal. The low-input chirpiness is magnified by the transformation material, and the error of the detection is kept approximately the same; thus, the designed lens has enhanced chirpiness detection precision and distinguishability for low chirpiness. The design is validated by numerical simulations.
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http://dx.doi.org/10.1364/AO.56.009119DOI Listing
November 2017

Diagnostic significance of microRNAs as novel biomarkers for bladder cancer: a meta-analysis of ten articles.

World J Surg Oncol 2017 Aug 3;15(1):147. Epub 2017 Aug 3.

Department of Urology, Ningxia People's Hospital, No. 301 North Zhengyuan Street, Jinfeng District, Yinchuan, 750021, Ningxia, China.

Background: Previous studies have revealed the importance of microRNAs' (miRNAs) function as biomarkers in diagnosing human bladder cancer (BC). However, the results are discordant. Consequently, the possibility of miRNAs to be BC biomarkers was summarized in this meta-analysis.

Methods: In this study, the relevant articles were systematically searched from CBM, PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI). The bivariate model was used to calculate the pooled diagnostic parameters and summary receiver operator characteristic (SROC) curve in this meta-analysis, thereby estimating the whole predictive performance. STATA software was used during the whole analysis.

Results: Thirty-one studies from 10 articles, including 1556 cases and 1347 controls, were explored in this meta-analysis. In short, the pooled sensitivity, area under the SROC curve, specificity, positive likelihood ratio, diagnostic odds ratio, and negative likelihood ratio were 0.72 (95%CI 0.66-0.76), 0.80 (0.77-0.84), 0.76 (0.71-0.81), 3.0 (2.4-3.8), 8 (5.0-12.0), and 0.37 (0.30-0.46) respectively. Additionally, sub-group and meta-regression analyses revealed that there were significant differences between ethnicity, miRNA profiling, and specimen sub-groups. These results suggested that Asian population-based studies, multiple-miRNA profiling, and blood-based assays might yield a higher diagnostic accuracy than their counterparts.

Conclusions: This meta-analysis demonstrated that miRNAs, particularly multiple miRNAs in the blood, might be novel, useful biomarkers with relatively high sensitivity and specificity and can be used for the diagnosis of BC. However, further prospective studies with more samples should be performed for further validation.
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http://dx.doi.org/10.1186/s12957-017-1201-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543742PMC
August 2017