Yi Li

Peking University Third Hospital, Peping, Beijing, China

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Publications (99)277.52 Total impact

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    ABSTRACT: Accumulated evidence has demonstrated that the microenvironment of a given tumor is important in determining its drug resistance, tumorigenesis, progression and metastasis. These microenvironments, like tumor cells, are vital targets for cancer therapy. The cross-talk between tumor cells and cancer-associated fibroblasts (CAFs, alternatively termed activated fibroblasts) is crucial in regulating the drug resistance, tumorigenesis, neoplastic progression, angiogenesis, invasion and metastasis of a tumor. Fibroblast activation protein α (FAPα) is a transmembrane serine protease and is highly expressed on CAFs present in >90% of human epithelial neoplasms. FAPα activity, alongside that of gelatinase and type I collagenase, has become increasingly important in cancer therapy due to its effectiveness in modulating tumor behavior. In this review, recent progression in the knowledge of the role of FAPα in tumor microenvironments is discussed.
    Molecular Medicine Reports 01/2015; · 1.48 Impact Factor
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    ABSTRACT: Introduction: Wild-type p53 gene is an essential cancer suppressor gene which plays an important role in carcinogenesis and malignant progressions. The p53 gene family participates in almost all the key procedures of cancer biology, such as programmed cell death, angiogenesis, metabolism and epithelial-mesenchymal transition. The mutation or functional defects of the p53 gene family are detected in most of the solid malignant tumors, and the restoration of the p53 gene by adenovirus-mediated gene therapy becomes a promising treatment for cancer patients now.Areas covered: In the present review, the potential therapeutic effects of recombinant adenovirus p53 rAd-p53 (Gendicine™) were reviewed to explore the biological mechanism underlying the adenovirus-mediated p53 gene therapy. Then, the key points of the drug administration were discussed, including the routes of administration, dosage calculation and treatment cycles, based on findings of the preclinical and clinical trials in order to establish a standard treatment for the p53 gene therapy.Expert opinion: As an important part of the combined therapy for the cancer patients, the adenovirus-mediated p53 gene therapy was blossomed to be a promising treatment strategy. A new evaluation criteria and guideline for the gene therapy is urgently needed for the further clinical practice.
    Expert Opinion on Biological Therapy. 12/2014;
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    ABSTRACT: To analyze the polymorphism of IL-22 gene in Han Chinese, and to evaluate the influence of IL-22 polymorphism on human immunodeficiency virus (HIV) infection.MethodsIL-22 gene polymorphism was analyzed in 73 healthy blood samples. The influence of the genotype and allele distribution of 3 single nucleotide polymorphisms (SNPs) (rs2227484, rs2227485, and rs2227513) of IL-22 on HIV infection was evaluated in 619 HIV seropositive patients and 619 healthy controls. To determine the association between rs2227513 genotype and IL-22 levels in plasma, we randomly selected 29 HIV seropositive blood samples and 15 healthy blood samples, and measured the levels of IL-22.ResultsNine SNPs loci (rs2227484, rs2227485, rs2227491, rs2227508, rs2227513, rs1179249, rs1179250, rs1179251, and rs1182844) of IL-22 gene were found. Stratified analysis (by gender) showed a higher association of HIV infection and A/G genotype and G allele at rs2227513 in females but not in males (A/G genotype: OR=5.24, 95% CI 1.13-24.27; allele G: OR=5.27, 95% CI 1.15-24.23). rs2227513 A/G genotype was also associated with significantly higher levels of plasma IL-22, regardless of whether HIV seropositive or seronegative.Conclusion Our results suggested that IL-22 production in blood might act as a pathogenic factor in HIV infection.
    Journal of Microbiology, Immunology and Infection. 11/2014;
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    ABSTRACT: Though HLA-DP/DQ is regarded to associate with HBV susceptibility and HBV natural clearance, its role in hepatocellular carcinoma (HCC) development is obscure. And the role of STAT4 in HBV susceptibility and clearance as well as HCC development is still contentious. Therefore, we conducted this study, aiming to clarify these obscure relationships.
    PLoS ONE 11/2014; 9(11):e111677. · 3.53 Impact Factor
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    ABSTRACT: The correct diagnosis and the prompt treatment of oral leukoplakia (OLK) can efficiently prevent OLK from undergoing malignant transformation to oral squamous cell carcinoma (OSCC). However, the diagnostic model in distinguishing normal mucosa from low-grade dysplasia as well as high-grade dysplasia from OSCC could not be better established in previous study. In this study, the characteristic wavenumbers in the Raman spectra were firstly identified by the feature selection methods. Then, the intensities at these wavenumbers were used to classify the biopsies. As results, the accuracies achieved by using the intensities at the characteristic wavenumbers were 70.5% and 94.0% for the classification of normal vs. low-grade dysplasia and high-grade dysplasia vs. OSCC, respectively, which were greater than those (accuracy = 65.4% and 88.0%, respectively) using all the intensities in the Raman spectra. Our results suggested constructing the diagnostic models with the intensities at the characteristic wavenumbers can improve the identification of the different lesions of oral mucosa. Moreover, most of the Raman intensities for predicting normal vs. low-grade dysplasia indicated the transformation from normal mucosa to low-grade dysplasia was associated with the changes in the contents of the lipids, while most of intensities for predicting high-grade dysplasia vs. OSCC indicated that the transformation from high-grade dysplasia to OSCC was associated with the changes in the contents of proteins and nucleic acids. Our findings can be helpful for diagnosing the various grades of OLK with dysplasia and understanding the molecular mechanisms of the potential malignant transformation of oral leukoplakia.
    Analytical methods 10/2014; · 1.94 Impact Factor
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    ABSTRACT: Bone marrow progenitor cells develop into mature megakaryocytes (MKs) to produce platelets for hemostasis and other physiological functions. However, the molecular mechanisms underlying megakaryopoiesis are not completely defined. We show that cytosolic carboxypeptidase (CCP) 6 deficiency in mice causes enlarged spleens and increased platelet counts with underdeveloped MKs and dysfunctional platelets. The prominent phenotypes of CCP6 deficiency are different from those of CCP1-deficient mice. We found that CCP6 and tubulin tyrosine ligase-like family (TTLL) members TTLL4 and TTLL6 are highly expressed in MKs. We identify Mad2 (mitotic arrest deficient 2) as a novel substrate for CCP6 and not CCP1. Mad2 can be polyglutamylated by TTLL4 and TTLL6 to modulate the maturation of MKs. CCP6 deficiency causes hyperglutamylation of Mad2 to promote activation of Aurora B, leading to suppression of MK maturation. We reveal that Mad2 polyglutamylation plays a critical role in the regulation of megakaryopoiesis.
    Journal of Experimental Medicine 10/2014; · 13.91 Impact Factor
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    ABSTRACT: The effect of changing temperature on an individual's cerebrovascular risk is both biologically plausible and supported by epidemiologic evidence. We used a global proteomic-based approach to analyze the expression alterations of proteins in artificial cold exposure (ACE)-induced hypertensive stroke in renovascular hypertensive rats (RHR) and to identify the biomarker of ACE-induced hypertensive stroke.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 10/2014; · 1.99 Impact Factor
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    ABSTRACT: Epidemiologic studies and meta-analyses have suggested that patients with type 2 diabetes mellitus (T2DM) have a higher incidence of malignancies, including myeloma. Metformin is a widely prescribed antidiabetic drug. Recently, researchers have shown that metformin has direct anticancer activity against many tumor cell lines, mainly through activating AMP-activated protein kinase (AMPK) or reducing the blood insulin level. In the present study, we investigated whether metformin exerts an anti-myeloma effect in vitro and in vivo xenograft models and explored the underlying mechanism. We found that metformin can inhibit proliferation of MM cells by inducing apoptosis and cell cycle arrest in the G0/G1 phase. Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6. Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR). IGF-I blocked metformin-induced MM cell apoptosis and reactivation of the PI3K/AKT/mTOR signaling pathway. Metformin also demonstrated synergistic activity with dexamethasone but not bortezomib to eradicate MM cells in vitro and in vivo, especially in MM.1S cells. We conclude that metformin inhibits MM cell proliferation through the IGF-1R/PI3K/AKT/mTOR signaling pathway. Metformin and dexamethasone combination therapy may be an option for MM treatment.
    Cancer Letters 10/2014; · 5.02 Impact Factor
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    ABSTRACT: Background Alcohol consumption induces inflammatory damage in vessels, and the underlying mechanism is unclear. Valsartan, as one of the angiotensin receptor blockers (ARBs), plays a role in the inhibition of inflammatory reactions in vascular dysfunction. This study is to investigate the role of Toll-like receptor 2 (TLR2) in alcohol-induced inflammatory damage in vascular endothelial cells in vitro and to explore the protective effect of valsartan on alcohol-induced and TLR2-mediated inflammatory damage.Methods The human umbilical vein cell line (EA.hy926) were exposed to alcohol at 0 to 80 mM for 0 to 48 hours with or without valsartan pretreatment. The expression of TLR2 signaling, including TLR2, tumor necrosis factor receptor associated factor 6 (TRAF-6) and nuclear factor kappa B (NF-κB) p65 were detected by Western blot. The levels of proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were determined by ELISA. To confirm the role of TLR2, we functionally up-regulated or down-regulated TLR2 by using TLR2 agonist or TLR2 small interfering RNA (siRNA), respectively. To further investigate the mechanism of alcohol on renin-angiotensin system, we detected the expression of angiotensin II receptor type 1 (AGTR1) in protein levels.ResultsThe expression of TLR2, TRAF-6, NF-κB p65, and the proinflammatory cytokines, TNF-α and IL-6, were significantly increased after alcohol exposure in EA.hy926 endothelial cells. This was enhanced by TLR2 agonist, and was inhibited by TLR2 siRNA transfection. The pretreatment of valsartan resulted in an inhibition of TLR2 signaling and proinflammatory cytokines. The expression of AGTR1 was up-regulated after alcohol exposure, and was blocked by valsartan pretreatment.ConclusionsTLR2 signaling-mediated alcohol induced inflammatory response in human vascular epithelial cells in vitro, which was inhibited by valsartan.
    Alcoholism Clinical and Experimental Research 10/2014; 38(10). · 3.31 Impact Factor
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    ABSTRACT: Background and AimStudies focused on the naturally occurring resistance mutation rate in treatment-naïve chronic hepatitis B (CHB) patients have set off a furious dispute. We conduct this meta-analysis to appraise the pooled incidence of spontaneous hepatitis B virus (HBV) resistance mutations worldwide and its distribution.Methods We searched PubMed, EMBASE, Chinese Biomedical Literature Database and China National Knowledge Infrastructure till December 31st, 2013. Cross-sectional or case-control studies reporting incidence of natural resistance mutations in untreated CHB patients were included. Pooled incidence was performed in fixed or random effects models, and heterogeneity among studies was assessed.ResultsA total of 106 studies were included involving 12212 naive CHB patients. The summarized incidence of natural mutations worldwide was 5.73% (95% confidence interval (CI): 4.85%-6.61%), primary mutation rate 5.39% (95%CI: 4.54%-6.24%) and secondary mutation rate 2.94% (95%CI: 1.59%–4.29%). The pooled incidence reached up to 8.00% (95%CI: 6.63%-9.38%) in China, higher than that in other countries(1.88% (95%CI: 1.06%-2.69%)). Mutation rtM204V/I had the highest incidence of 4.89% (95%CI: 4.13%-5.65%), and other primary mutations seldom spontaneously occurred. In subgroup analysis, genotype C HBV infection, male and hepatitis B antigen (HBeAg) negative patients had a slightly higher natural mutation rate.Conclusions The resistance mutations occurred frequently in untreated CHB patients, especially in China. The lamivudine resistance had the highest natural prevalence rate, while other nucleos(t)ide analogues showed rarely spontaneous resistance. Detecting the spontaneous resistance mutations will benefit the clinical management of CHB patients.
    Journal of Gastroenterology and Hepatology 10/2014; · 3.33 Impact Factor
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    ABSTRACT: Astaxanthin is a strong antioxidant with the ability of reducing the markers of inflammation. To explore the protective effect of astaxanthin on maternal ethanol induced embryonic deficiency, and to investigate the underlying mechanisms, we detected the morphology, expression of neural marker genes, oxidative stress indexes, and inflammatory factors in mice model of fetal alcohol spectrum disorder with or without astaxanthin pretreatment. Our results showed that astaxanthin blocked maternal ethanol induced retardation of embryonic growth, and the down-regulation of neural marker genes, Otx1 and Sox2. Moreover, astaxanthin also reversed the increases of malondialdehyde (MDA), hydrogen peroxide (H2O2), and the decrease of glutathione peroxidase (GPx) in fetal alcohol spectrum disorder. In addition, maternal ethanol induced up-regulation of toll-like receptor 4 (TLR4), and the down-streaming myeloid differentiation factor 88 (MyD88), NF-κB, TNF-α, and IL-1β in embryos, and this was inhibited by astaxanthin pretreatment. These results demonstrated a protective effect of astaxanthin on fetal alcohol spectrum disorder, and suggested that oxidative stress and TLR4 signaling associated inflammatory reaction are involved in this process.
    Neuropharmacology 09/2014; 84:13–18. · 4.82 Impact Factor
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    ABSTRACT: The preoperative and intraoperative diagnosis of parotid gland tumors is difficult, but is important for their surgical management. In order to explore an intraoperative diagnostic method, Raman spectroscopy is applied to detect the normal parotid gland and tumors, including pleomorphic adenoma, Warthin's tumor and mucoepidermoid carcinoma. In the 600–1800 cm−1 region of the Raman shift, there are numerous spectral differences between the parotid gland and tumors. Compared with Raman spectra of the normal parotid gland, the Raman spectra of parotid tumors show an increase of the peaks assigned to nucleic acids and proteins, but a decrease of the peaks related to lipids. Spectral differences also exist between the spectra of parotid tumors. Based on these differences, a remarkable classification and diagnosis of the parotid gland and tumors are carried out by support vector machine (SVM), with high accuracy (96.7~100%), sensitivity (93.3~100%) and specificity (96.7~100%). Raman spectroscopy combined with SVM has a great potential to aid the intraoperative diagnosis of parotid tumors and could provide an accurate and rapid diagnostic approach.
    Laser Physics 08/2014; 24(11):115601. · 1.03 Impact Factor
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    ABSTRACT: Whether clopidogrel should be added to aspirin for stroke prevention remained controversial for the risk of hemorrhagic complications. This meta-analysis was aimed to assess the efficacy and safety of adding clopidogrel to aspirin on stroke prevention in high vascular risk patients, and to provide evidence for a suitable duration of dual antiplatelet therapy.
    PLoS ONE 08/2014; 9(8):e104402. · 3.53 Impact Factor
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    ABSTRACT: Noradrenergic pathways and glucocorticoid-mediated signal pathways have been implicated in the growth and progression of oral cancer. Patients with oral neoplasms can have high psychological distress levels, but the effects of stress-related hormones on oral neoplasm growth are unknown.
    PLoS ONE 07/2014; 9(7):e99179. · 3.53 Impact Factor
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    ABSTRACT: Multiple myeloma (MM) is a malignant plasma cells proliferative disease. The intricate cross-talk of myeloma cells with bone marrow microenvironment plays an important role in facilitating growth and survival of myeloma cells. Bone marrow mesenchymal stem cells (BMMSCs) are important cells in MM microenvironment. In solid tumors, BMMSCs can be educated by tumor cells to become cancer-associated fibroblasts (CAFs) with high expression of fibroblast activation protein (FAP). FAP was reported to be involved in drug resistance, tumorigenesis, neoplastic progression, angiogenesis, invasion and metastasis of tumor cells. However, the expression and the role of FAP in MM bone marrow microenvironment is still less known. The present study is aimed to investigate the expression of FAP, the role of FAP and its relevant signaling pathway in regulating apoptosis induced by bortezomib in MM cells. In this study, our data illustrated that the expression levels of FAP were not different between the cultured BMMSCs isolated from MM patients and normal donors. The expression levels of FAP can be increased by TCCM stimulation or coculture with RPMI8226 cells. FAP has important role in BMMSCs mediated protecting MM cell lines from apoptosis induced by bortezomib. Further study showed that this process may likely through β-catenin signaling pathway in vitro. The activation of β-catenin in MM cell lines was dependent on direct contact with BMMSCs other than separated by transwell or additional condition medium from BMMSCs and cytokines.
    Cancer biology & therapy 07/2014; 15(10). · 3.63 Impact Factor
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    ABSTRACT: Several genome-wide association studies have revealed that HLA-DP/DQ, STAT4 and IL-28B associated with liver diseases. But due to population heterogeneity, different races would have different causative polymorphisms. Therefore, in this study, we included Chinese Tibetans and Uygurs to examine the roles of these genes on HBV natural clearance.
    Liver international: official journal of the International Association for the Study of the Liver 07/2014; · 4.41 Impact Factor
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    ABSTRACT: In recent years, sodium taurocholate cotransporting polypeptide (NTCP) was newly identified as a hepatitis B virus (HBV) receptor, which partly shed light on the reason for HBV hepatotropism and its host specificity. However, the related researches were limited to in-vitro or animal experiments. Therefore, this study aimed to investigate the association of NTCP polymorphisms with HBV natural course in humans.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 07/2014; · 3.22 Impact Factor
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    ABSTRACT: Changes in the actin cytoskeleton in neurons are associated with synaptic plasticity and may also be involved in mechanisms of nociception. We found that the LIM motif-containing protein kinases (LIMKs), which regulate actin dynamics, promoted the development of inflammatory hyperalgesia (excessive sensitivity to painful stimuli). Pain is sensed by the primary sensory neurons of dorsal root ganglion (DRG). In rats injected with complete Freund's adjuvant (CFA), which induces inflammatory heat hyperalgesia, DRG neurons showed an increase in LIMK activity and in the phosphorylation and thus inhibition of the LIMK substrate cofilin, an actin-severing protein. Manipulations that reduced LIMK activity or abundance, prevented the phosphorylation of cofilin, or disrupted actin filaments in DRG neurons attenuated CFA-induced heat hyperalgesia. Inflammatory stimuli stimulated actin polymerization and enhanced the response of the cation channel TRPV1 (transient receptor potential V1) to capsaicin in DRG neurons, effects that were reversed by the knockdown of LIMK or preventing cofilin phosphorylation. Furthermore, inflammatory stimuli caused the serine phosphorylation of TRPV1, which was abolished by preventing cofilin phosphorylation in DRG neurons. We conclude that LIMK-dependent actin rearrangement in primary sensory neurons, leading to altered TRPV1 sensitivity, is involved in the development of inflammatory hyperalgesia.
    Science Signaling 06/2014; 7(331):ra61. · 7.65 Impact Factor
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    ABSTRACT: Objective: To explore the correlation of blood-cerebrospinal fluid (CSF) barrier (BCB) dysfunction with the therapeutic effect of antitubercular agents and their resistance, hoping to provide theoretical evidence for improvement of the therapeutic effect. Methods: Albumin in CSF and serum was assayed by IMMAGE. The CSF/serum albumin ratio (QALB) was used to evaluate the permeability of the BCB. Real-time fluorescence quantitative PCR was used to detect the amount of Mycobacterium tuberculosis DNA, and an MTBDRplus reagent kit was used to determine the type of drug resistance of the M. tuberculosis. Results: The correlation analysis showed that significant correlation existed between the grade of severity of tuberculous meningitis and the QALB, and the grade of severity and the total leukocyte count in the CSF, for which the correlation coefficients were 0.366 (p < 0.05) and 0.365 (p < 0.05), respectively. The QALB in the group of patients who recovered was significantly higher than that in those patients who experienced disease progression (p = 0.019). Conclusions: Our study showed that the permeability of the BCB correlated with the cure rate in tuberculous meningitis. Specifically, in the treatment of tuberculous meningitis, it is of key importance to utilize the benefit of the permeability of the BCB to achieve a better outcome. © 2014 S. Karger AG, Basel.
    European Neurology 04/2014; 71(5-6):331-336. · 1.36 Impact Factor
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    ABSTRACT: In past 2 decades, nonmedical consumption of cough mixture has become a serious social problem in certain regions of China. Cough mixture abuse causes psychiatric symptoms. Moreover, there has been an increasing concern about the physical disorders associated with cough mixture abuse. A retrospective chart review of hypokalemia related to cough mixture abuse between January 2009 and December 2012 was conducted in Guangzhou Brain Hospital, China. The charts were reviewed for 34 subjects with cough mixture abuse. Seven of 34 cough mixture abusers (20.6%) presented hypokalemia, with symptoms ranged from mild to severe limb weakness. Hypokalemia in these patients reduced after normalization of potassium. A high incidence of hypokalemia presents in cough mixture abusers. Cough mixture abuse might be one of the secondary causes of hypokalemia paralysis in young patients presenting to emergency departments.
    Journal of Addiction Medicine 04/2014; · 1.71 Impact Factor

Publication Stats

647 Citations
277.52 Total Impact Points


  • 2014
    • Peking University Third Hospital
      Peping, Beijing, China
  • 2008–2014
    • Sun Yat-Sen University
      • School of Life Sciences
      Shengcheng, Guangdong, China
  • 2007–2014
    • Sichuan University
      • • Department of Laboratory Medicine
      • • Biomedical Engineering Unit
      • • Department of Immunology
      Hua-yang, Sichuan, China
    • Peking University
      • • School of Basic Medical Science
      • • Neuroscience Research Institute
      Peping, Beijing, China
    • Peking University Health Science Center
      Peping, Beijing, China
  • 2012
    • Zhejiang University
      • School of Medicine
      Hang-hsien, Zhejiang Sheng, China
  • 2008–2011
    • East Tennessee State University
      • Department of Internal Medicine
      Johnson City, TN, United States
  • 2010
    • Peking University People's Hospital
      Peping, Beijing, China