Qi Li

Harbin Medical University, Charbin, Heilongjiang Sheng, China

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Publications (9)30.26 Total impact

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    ABSTRACT: Delta-like ligand 4 (DLL4), one of the five Notch signaling ligands in mammals, has an important function in proliferation, invasion, metastasis, progression, and angiogenesis of malignancies. This study aimed to investigate DLL4 expression level in early-stage cervical carcinoma and to evaluate its clinical significance. We used fresh frozen and paraffin-embedded cervical cancer tissues to analyze DLL4 expression and its clinical significance. DLL4 expression at both mRNA and protein levels in cervical cancer tissues was significantly higher than that in normal cervical tissues. High DLL4 protein level was clearly correlated with high International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.044), lymphovascular space involvement (LVSI) (P = 0.015), pelvic lymph node metastasis (PLNM) (P = 0.001), and recurrence (P < 0.001). Univariate and multivariate logistic regression analyses demonstrated that DLL4 overexpression was strongly associated with lymph node metastasis (odds ratio, 2.790; 95 % CI, 1.344-5.791; P = 0.006). Moreover, survival analysis revealed that DLL4 expression was an independent factor of unfavorable overall survival (hazard ratio, 2.130; 95 % CI, 1.108-4.097; P = 0.023) and disease-free survival (hazard ratio, 1.965; 95 % CI, 1.085-3.560; P = 0.026) in patients with cervical cancer. Overall, our data indicate that high DLL4 expression predicts pelvic lymph node metastasis and poor survival in cervical cancer. Therefore, DLL4 may be a potential clinical diagnostic marker for patients with early-stage cervical cancer.
    No preview · Article · Nov 2015 · Tumor Biology
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    ABSTRACT: Concurrent chemoradiotherapy (cCRT) is the standard of care for International Federation of Gynecology and Obstetrics (FIGO) stage IIB squamous cervical carcinoma (SCC). However, an increasing number of young patients with stage IIB SCC are concerned with preserving their ovarian and vaginal functions during treatment. This retrospective study aimed to compare clinical prognosis between young patients with stage IIB SCC treated with neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) and those treated with cCRT. Medical records of 244 premenopausal patients aged <45 years with FIGO stage IIB SCC treated with NACT+RS and cCRT between February 2007 and June 2009 were reviewed. All these patients completed the treatment plan. NACT+RS resulted in recurrence (35.9 versus 41.8 %, P = 0.350), progression-free survival (PFS) rate (log-rank, P = 0.456), and overall survival (OS) rate (log-rank, P = 0.637) comparable to cCRT. Compared with cCRT, NACT+RS did not show a significant statistical difference in clinical prognosis of premenopausal patients with stage IIB SCC. Therefore, NACT+RS may be considered as an alternative treatment for the young patients who are concerned with preserving endocrine function, and this alternative treatment may also be administered when radiotherapy is unavailable.
    No preview · Article · Jan 2015 · Tumor Biology
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    ABSTRACT: Cardiac T-type Ca(2+) channels are reexpressed in atrial and ventricular myocytes under various pathological conditions such as post-myocardial infarction, hypertrophy, and heart failure, but relatively little is known about the mechanisms. Our previous study found that bone morphogenetic protein-4 (BMP4) was reexpressed in pathological cardiac hypertrophy models and BMP4-mediated cardiomyocyte hypertrophy. We hypothesized that BMP4 could upregulate cardiac T-type Ca(2+) channels in HL-1 atrial myocytes. The T-type Ca(2+) currents were recorded by using the patch-clamp technique, and the expressions of Cav3.1 and Cav3.2 were measured by real-time PCR method in HL-1 cells. BMP4 and Cav3.1 mRNA expressions increased in the left atrium from the pressure overload-induced hypertrophy of mice hearts. BMP4 treatment for 48 h induced increase of Cav3.1 but not Cav3.2 mRNA expression in HL-1 cells, and the increase was inhibited by BMP4 inhibitor noggin. Acute treatment with BMP4 did not affect T-type Ca(2+) currents, but chronic treatment (48 h) significantly increased the amplitude of T-type Ca(2+) currents in HL-1 cells. Chronic treatment with BMP4 induced upregulation of NADPH oxidase-4 (NOX4), increase of reactive oxygen species (ROS) level, and activation of mitogen-activated protein kinase (MAPK)-activated protein kinases c-jun N-terminal kinases (JNK) and p38. BMP4-induced upregulation of Cav3.1 mRNA was inhibited by NADPH oxidase inhibitor apocynin, the radical scavenger tempol, JNK inhibitor SP600125, and p38 inhibitor SB203580. In conclusion, BMP4 induces upregulation of Cav3.1 Ca(2+) channels and T-type Ca(2+) currents in HL-1 atrial myocytes through ROS/MAPK pathways.
    No preview · Article · Feb 2014 · Pflügers Archiv - European Journal of Physiology
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    ABSTRACT: Integrin-linked kinase (ILK) plays a role in the regulation of multiple cellular functions (e.g., promoting cell migration and proliferation, but inhibiting cell adhesion). This study investigated the inhibitory effects of ILK gene knockdown on the regulation of in vivo tumorigenesis of human ovarian carcinoma cells in nude mouse xenografts. HO-8910 cells were transfected with an ILK antisense oligonucleotide (ILK-ASO) to silence the ILK gene. Expression of ILK mRNA and protein was evaluated by RT-PCR and western blotting, respectively. The cell cycle was assessed by flow cytometric analysis. Cells with or without ILK-ASO transfection were subcutaneously injected into nude mice. The mouse body weight, tumor formation, tumor size and tumor weight were determined up to 30 days after inoculation. Tumor cells transfected with ILK-ASO had significantly decreased ILK mRNA and protein expression (P<0.01) when compared to the control cells. ILK gene silencing significantly increased the number of cells in the G0/G1 phase (67.61 vs. 43.29%, χ2=1197.15, P<0.01). After tumor cell inoculation, tumor cells transfected with ILK-ASO showed significantly delayed tumor formation when compared to control (9.10±0.74 vs. 5.30±0.67 days, respectively; P<0.01). In addition, tumor growth was suppressed in the 30 days following inoculation (P<0.01 compared with the controls). The average tumor weight in the ILK-ASO group was statistically lower than that of the control group (1.29±0.11 vs. 1.57±0.13 g, respectively; P<0.01). This study demonstrated that ILK-ASO transfection efficiently downregulated ILK expression in human ovarian carcinoma HO-8910 cells and that ILK gene silencing suppressed tumor growth in nude mice xenografts.
    Preview · Article · Jan 2013 · Molecular Medicine Reports
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    ABSTRACT: Background: Sentinel surveillance of Keshan disease (KD) is limited by unable to give the prevalence rates and their estimates. This study was to find the national KD prevalence and the estimated patient numbers to provide evidence toward modifying the policy of KD prevention and control. Method: Using a probability proportional to population size, randomized, multistage, and cluster sampling, we surveyed 101,127, measured grain selenium levels; and surveyed household income with pre-designed questionnaires. Results: The national prevalence rates of KD, chronic KD and latent KD were 2.21%, 0.50%, and 1.71% respectively. Chronic KD patients are mainly in the provinces where KD had been seriously epidemic. The KD prevalence rate was higher in females (2.20%) than in males (1.98%). These were also higher in older age groups. The cases younger than 30 years accounted for 13.6%, indicating the possibility that KD is still occurring. Nationally, the estimated numbers of KD and chronic KD patients are 1,675,500 (95% CI, 1,608,500-1,747,300) and 379,800 (95% CI, 346,700-412,800) respectively. Multiple logistic regression analysis indicated that family income was a significant dependent variable (OR: -0.258, 95% CI: -0.332 to -0.185, p<0.001). More than 2000 chronic KD patients found in the study were treated in 2009-2011. The limitation of this study was that sampling size was determined at national level. Conclusion: KD is still a public health issue among the people of the historically severe endemic areas. Selenium supplementation, self-management program for chronic KD patients and translation epidemiology of KD surveillance should be strengthened.
    No preview · Article · Dec 2012 · International journal of cardiology
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    ABSTRACT: Background To quantitatively evaluate the safety and related-toxicities of intensity modulated radiotherapy (IMRT) dose–volume histograms (DVHs), as compared to the conventional three-dimensional conformal radiotherapy (3D-CRT), in gynecologic malignancy patients by systematic review of the related publications and meta-analysis. Methods Relevant articles were retrieved from the PubMed, Embase, and Cochrane Library databases up to August 2011. Two independent reviewers assessed the included studies and extracted data. Pooled average percent irradiated volumes of adjacent non-cancerous tissues were calculated and compared between IMRT and 3D-CRT for a range of common radiation doses (5-45Gy). Results In total, 13 articles comprised of 222 IMRT-treated and 233 3D-CRT-treated patients were included. For rectum receiving doses ≥30 Gy, the IMRT pooled average irradiated volumes were less than those from 3D-CRT by 26.40% (30 Gy, p = 0.004), 27.00% (35 Gy, p = 0.040), 37.30% (40 Gy, p = 0.006), and 39.50% (45 Gy, p = 0.002). Reduction in irradiated small bowel was also observed for IMRT-delivered 40 Gy and 45 Gy (by 17.80% (p = 0.043) and 17.30% (p = 0.012), respectively), as compared with 3D-CRT. However, there were no significant differences in the IMRT and 3D-CRT pooled average percent volumes of irradiated small bowel or rectum from lower doses, or in the bladder or bone marrow from any of the doses. IMRT-treated patients did not experience more severe acute or chronic toxicities than 3D-CRT-treated patients. Conclusions IMRT-delivered high radiation dose produced significantly less average percent volumes of irradiated rectum and small bowel than 3D-CRT, but did not differentially affect the average percent volumes in the bladder and bone marrow.
    Preview · Article · Nov 2012 · Radiation Oncology
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    ABSTRACT: Down-regulation of Kv4.3 K⁺ channels commonly occurs in multiple diseases, but the understanding of the regulation of Kv4.3 K⁺ channels and the role of Kv4.3 K⁺ channels in pathological conditions are limited. HEK (human embryonic kidney)-293T cells are derived from HEK-293 cells which are transformed by expression of the large T-antigen. In the present study, by comparing HEK-293 and HEK-293T cells, we find that HEK-293T cells express more Kv4.3 K⁺ channels and more transcription factor Sp1 (specificity protein 1) than HEK-293 cells. Inhibition of Sp1 with Sp1 decoy oligonucleotide reduces Kv4.3 K⁺ channel expression in HEK-293T cells. Transfection of pN3-Sp1FL vector increases Sp1 protein expression and results in increased Kv4.3 K⁺ expression in HEK-293 cells. Since the ultimate determinant of the phenotype difference between HEK-293 and HEK-293T cells is the large T-antigen, we conclude that the large T-antigen up-regulates Kv4.3 K⁺ channel expression through an increase in Sp1. In both HEK-293 and HEK-293T cells, inhibition of Kv4.3 K⁺ channels with 4-AP (4-aminopyridine) or Kv4.3 small interfering RNA induces cell apoptosis and necrosis, which are completely rescued by the specific CaMKII (calcium/calmodulin-dependent protein kinase II) inhibitor KN-93, suggesting that Kv4.3 K⁺ channels contribute to cell apoptosis and necrosis through CaMKII activation. In summary, we establish: (i) the HEK-293 and HEK-293T cell model for Kv4.3 K⁺ channel study; (ii) that large T-antigen up-regulates Kv4.3 K⁺ channels through increasing Sp1 levels; and (iii) that Kv4.3 K⁺ channels contribute to cell apoptosis and necrosis through activating CaMKII. The present study provides deep insights into the mechanism of the regulation of Kv4.3 K⁺ channels and the role of Kv4.3 K⁺ channels in cell death.
    Preview · Article · Feb 2012 · Biochemical Journal
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    ABSTRACT: This study explores whether the declining prevalence of Keshan disease is associated with increasing selenium levels in Keshan disease areas in Heilongjiang province. Six counties endemic with Keshan disease and three non-endemic counties were selected as study areas. In each county, two townships and in each township one village were chosen in which to survey ten families about head hair, grain, and soil samples and to obtain demographic information. Selenium was measured with hydride generation-atomic fluorescence spectrometry. In each county endemic with Keshan disease, one of the villages was chosen to investigate the prevalence of the disease. We collected 534 head hair samples, 446 staple food samples, and 180 soil samples. The selenium levels of head hair and corn in the endemic counties were significantly lower than those in non-endemic counties. Family demographic information was homologous except for the composition of staple food. More residents in Keshan disease areas preferred flour and corn. The detection rate for latent Keshan disease had a significantly negative correlation with the corn selenium level in six counties endemic with Keshan disease. As the population in this region is still at risk for Keshan disease, selenium surveillance measures should be intensified.
    No preview · Article · Dec 2011 · Biological trace element research
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    ABSTRACT: HIV-infected patients have a high prevalence of long QT syndrome (LQTs). hERG K(+) channel encoded by human ether-a-go-go related gene contributes to IKr K(+) currents responsible for the repolarization of cardiomyocytes. Inhibition of hERG K(+) channels leads to LQTs. HIV Tat protein, the virus transactivator protein, plays a pivotal role in AIDS. The aim of the present study is to examine the effects of HIV Tat protein on hERG K(+) channels stably expressed in HEK293 cells. The hERG K(+) currents were recorded by whole-cell patch-clamp technique and the hERG channel expression was measured by real-time PCR and Western blot techniques. HIV Tat protein at 200 ng/ml concentration showed no acute effect on hERG currents, but HIV Tat protein (200 ng/ml) incubation for 24 h significantly inhibited hERG currents. In HIV Tat incubated cells, the inactivation and the recovery time from inactivation of hERG channels were significantly changed. HIV Tat protein incubation (200 ng/ml) for 24h had no effect on the hERG mRNA expression, but dose-dependently inhibited hERG protein expression. The MTT assay showed that HIV Tat protein at 50 ng/ml and 200 ng/ml had no effect on the cell viability. HIV Tat protein increased reactive oxygen species (ROS) generation and the inhibition of hERG channel protein expression by HIV Tat protein was prevented by antioxidant tempol. HIV Tat protein in vivo treatment reduced IKr currents and prolonged action potential duration of guinea pig cardiomyocytes. We conclude that HIV Tat protein inhibits hERG K(+) currents through the inhibition of hERG protein expression, which might be the potential mechanism of HIV infection induced LQTs.
    No preview · Article · Jul 2011 · Journal of Molecular and Cellular Cardiology