Publications by authors named "Yanmin Ma"

27 Publications

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Follicular Metabolites-Assisted Clinical Evaluation of IVF/ICSI Outcomes.

Evid Based Complement Alternat Med 2021 26;2021:9999659. Epub 2021 May 26.

Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.

As infertility became a significant public health problem, assisted reproductive technologies (ARTs) were introduced. However, the fertilization rate of in vitro fertilization (IVF) per cycle varied, and patients needed to repeat IVF or change to intracytoplasmic sperm injection (ICSI). Here, 75 couples suffering from female fallopian tubal blockage (tubal group) and 42 spouses beset by male abnormal sperm status (dysspermia group) were recruited. We comprehensively explored the relationship among couples' clinical factors, follicular metabolites, and IVF/ICSI stepwise outcomes. IVF/ICSI outcomes were affected by follicular metabolites and physical status in both women and men, regardless of which side infertility came from. Particularly, in the tubal group, the energy supporting pathways-glycolysis and pyruvate metabolism-were most essential in follicles, and IVF/ICSI outcomes were also related to sperm parameters. However, in the dysspermia group, in addition to sperm conditions, oocyte quality acted as a compensation for poor sperm quality, for which aminoacyl-tRNA biosynthesis and the related supporting metabolism were critical in the follicular environment, and ultimately played a decisive role in IVF/ICSI outcomes. The respective logistic regression models in combination with selective male sperm parameters, estradiol (E2), follicular alanine, glutamine, glycoprotein, lipid, and acetic acid, were constructed to predict IVF or ICSI outcomes. No matter which sex infertility comes from, factors from both men and women should be considered. The current study provides a feasible option for pre-IVF evaluation, as well as guidance for follow-up clinical intervention to improve IVF/ICSI success rates.
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http://dx.doi.org/10.1155/2021/9999659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189786PMC
May 2021

The effects of multiple controlled ovarian hyperstimulation over a 2-year period on ovarian reserve and reactivity: a retrospective clinical study.

Ann Palliat Med 2021 Apr;10(4):4391-4397

Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Background: To evaluate the effects of controlled ovarian hyperstimulation (COH) on ovarian reserve function during in vitro fertilization and embryo transfer (IVF-ET).

Methods: From August 2018 to August 2020, the medical records of patients who received IVF-ET in the Department of Reproductive Medicine, Beijing Gynaecology and Obstetrics Hospital, Capital Medical University were analyzed retrospectively. Among them, 372 patients received 2 cycles of COH, 54 patients received 3 cycles, and 13 patients received 4 cycles. The levels of follicle-stimulating hormone (FSH), the number of antral follicles, levels of anti-Müllerian hormone (AMH), the total amount of gonadotropin (GN), the time of ovulation induction, the number of eggs obtained, the number of available embryos, and the number of high-quality embryos cycles were compared in different treatment.

Results: The age of female patients did not significantly affect the levels of AMH or FSH during menstruation, nor the number of antral follicles before ovulation induction (P>0.05). However, with an increase in age, an increase in the number of controlled COH cycles was observed. In patients who underwent 2 COH cycles, the number of high-quality embryos in the second cycle increased significantly compared to the first cycle (P<0.05). However, there were no significant differences in the ovulation induction time, the number of eggs, the GN dosage, and the number of available embryos (P>0.05). In patients with 3 treatment cycles, the GN dose used in the third cycle was significantly lower than that used in the first cycle (P<0.05). There were no significant differences in the ovulation induction time, the number of eggs obtained, and the quality of embryos (P>0.05). In patients with 4 treatment cycles, significant differences were observed in the ovulation induction time between the first and the fourth controlled COH cycle (P<0.05). However, no significant differences were detected in GN dosage, ovulation induction time, the number of eggs obtained, the number of available embryos, and the quality of embryos (P>0.05).

Conclusions: Ovarian reserve function was not significantly affected in patients with up to 4 ovarian stimulation cycles.
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http://dx.doi.org/10.21037/apm-21-330DOI Listing
April 2021

Oestrogen induces epithelial-mesenchymal transition in endometriosis via circ_0004712/miR-148a-3p sponge function.

J Cell Mol Med 2020 09 15;24(17):9658-9666. Epub 2020 Jul 15.

Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Endometriosis is a common, chronic gynaecologic disease affecting up to 10% of women in their reproductive age and leading to pain and infertility. Oestrogen (E )-induced epithelial-mesenchymal transition (EMT) process has been considered as a key factor of endometriosis development. Recently, the dysregulated circular RNAs (circRNAs) have been discovered in endometriosis tissues. However, the molecular mechanism of circRNAs on the E -induced EMT process in endometriosis is still unknown. Here, we demonstrated that circ_0004712 up-regulated by E treatment in endometrial epithelial cells. Knock-down the expression of circ_0004712 significantly suppressed E -induced cell migration activity. Meanwhile, we identified miR-148a-3p as a potential target miRNA of circ_0004712. Inhibited the expression of miR-148a-3p could recovered the effect of circ_0004712 knock-down in E -treated endometrial epithelial. Furthermore, Western blot assay showed that E treatment could increase the expression and activity of β-catenin, snail and N-cadherin and reduce the expression of E-cadherin. The expression and activity of β-catenin pathway were recovered by circ_0004712 knock-down or miR-148a-3p overexpression. Altogether, the results demonstrate that circ_0004712/miR-148a-3p plays an important role in E -induced EMT process in the development of endometriosis, and the molecular mechanism may be associated with the β-catenin pathway. This work highlighted the importance of circRNAs in the development of endometriosis and provide a new biomarker for diagnosis and therapies.
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http://dx.doi.org/10.1111/jcmm.15495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520264PMC
September 2020

LncRNA SNHG4 promotes the increased growth of endometrial tissue outside the uterine cavity via regulating c-Met mediated by miR-148a-3p.

Mol Cell Endocrinol 2020 08 7;514:110887. Epub 2020 Jun 7.

Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, PR China. Electronic address:

Long noncoding RNAs (lncRNAs) modulate endometriosis. The current study investigated the mechanisms and effects of SNHG4 on endometriosis. The qRT-PCR was conducted to examine the miR-148a-3p and SNHG4 expressions in endometriosis tissues. The 5-ethynyl-2'-deoxyuridine incorporation assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay were used to measure the rate of cell proliferation. The association between miR-148a-3p, SNHG4 and c-Met was confirmed via bioinformatical approach and luciferase reporter gene assay. Also, the function of SNHG4 on the growth of endometriotic lesions was investigated in vivo. The SNHG4 expression was considerably upregulated in endometriosis tissues, whereas the level of miR-148a-3p expression was reduced. In addition, SNHG4 can be considered as ceRNAs that bind miR-148a-3p and rise the proliferation activity of HESCs by downregulating miR-148a-3p. Furthermore, silencing SNHG4 could downregulate the c-Met level by enhancing miR-148a-3p expression, and finally inhibiting endometriosis development in vivo. LncRNA SNHG4 promotes the increased growth of endometrial tissue outside the uterine cavity via regulating c-Met mediated by miR-148a-3p, which may be used as diagnostic biomarker as well as molecular target in the treatment of endometriosis.
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http://dx.doi.org/10.1016/j.mce.2020.110887DOI Listing
August 2020

Loss of hsa_circ_0118530 inhibits human granulosa-like tumor cell line KGN cell injury by sponging miR-136.

Gene 2020 Jun 24;744:144591. Epub 2020 Mar 24.

Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, PR China. Electronic address:

Polycystic ovary syndrome (PCOS) is a kind of endocrine disease among women across the global. Recently, many researches have reported circular RNAs can act as significant molecular biomarkers for diseases, especially in tumors. Several Circular RNAs are reported to be aberrantly expressed in PCOS patients. Here, we investigated the biological effects of hsa_circ_0118530 on human granulosa cells, KGN. We observed that hsa_circ_0118530 was greatly elevated in PCOS patients and granulosa cells (including KGN and COV434 cells) compared to normal IOSE80 cells. hsa_circ_0118530 siRNA was transfected into KGN cells. We found that KGN cell viability was repressed, cell apoptosis was induced while cell migration was greatly inhibited. TGF-β1 was utilized to induce EMT process. As shown, loss of hsa_circ_0118530 significantly enhanced E-cadherin mRNA and protein levels while depressed N-cadherin expression. Furthermore, we indicated that decrease of hsa_circ_0118530 was able to inhibit ROS accumulation, MDA levels while induced SOD activity. Next, it was demonstrated that releases of inflammatory cytokine were suppressed by hsa_circ_0118530 down-regulation. Additionally, miR-136 was predicted and confirmed as the target of hsa_circ_0118530. For another, the functions of hsa_circ_0118530 on KGN cell progression, oxidative stress and inflammation releases were obviously reversed by miR-136 suppression. In conclusion, knockdown of hsa_circ_0118530 repressed PCOS progression via sponging miR-136.
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http://dx.doi.org/10.1016/j.gene.2020.144591DOI Listing
June 2020

Effects of environmental contaminants on fertility and reproductive health.

J Environ Sci (China) 2019 Mar 22;77:210-217. Epub 2018 Aug 22.

Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Recent research indicates that the human infertility rate is increasing. Although various reasons have been hypothesized for the growing infertility rate, environmental contaminants are potentially important causal agents associated with this change. Chemical contaminants are widespread throughout our environment and human exposure is virtually unavoidable. The overall contribution of environmental exposure to infertility is unknown, but studies involving occupational exposure, together with results from animal experiments, suggest that environmental contaminants may adversely affect fertility. We reviewed the adverse effects of environmental exposure on fertility and related reproductive outcomes. Environmental contaminants covered in this review include heavy metals, organic solvents, pesticides and endocrine disrupting chemicals. It is hoped that this review will highlight the need for further research in this area.
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http://dx.doi.org/10.1016/j.jes.2018.07.015DOI Listing
March 2019

The Kidney Injury Induced by Short-Term PM Exposure and the Prophylactic Treatment of Essential Oils in BALB/c Mice.

Oxid Med Cell Longev 2018 29;2018:9098627. Epub 2018 Jul 29.

College of Medical Laboratory, Dalian Medical University, Dalian, Liaoning Province 116044, China.

PM is well known as a major environmental pollutant; it has been proved to be associated with kidney diseases. The kidney damage involves oxidative stress and/or inflammatory response. NOX4 is a major source of reactive oxygen species (ROS) generation in the kidney, and the excessive generation of ROS is recognized to be responsible for oxidative stress. To elucidate whether short-term PM exposure could induce kidney damage, we exposed BALB/c mice to PM intratracheally and measured the biomarkers of kidney injury (KIM-1, cystatin C), oxidative stress (MDA, SOD-1, and HO-1), and inflammatory response (NF-B, TNF-). Acute kidney damage and excessive oxidative stress as well as transient inflammatory response were observed after PM installation. The overexpression of some components of the angiotensin system (RAS) after PM exposure illustrated that RAS may be involved in PM-induced acute kidney injury. CEOs (compound essential oils) have been widely used because of their antioxidant and anti-inflammation properties. Treatment with CEOs substantially attenuated PM-induced acute kidney injury. The suppression of RAS activation was significant and earlier than the decrease of oxidative stress and inflammatory response after CEOs treatment. We hypothesized that CEOs could attenuate the acute kidney injury by suppressing the RAS activation and subsequently inhibit the oxidative stress and inflammatory response.
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http://dx.doi.org/10.1155/2018/9098627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087578PMC
December 2018

Liver injury induced in Balb/c mice by PM exposure and its alleviation by compound essential oils.

Biomed Pharmacother 2018 Sep 8;105:590-598. Epub 2018 Jun 8.

College of Medical Laboratory, Dalian Medical University, Dalian, 116044, Liaoning Province, People's Republic of China. Electronic address:

Accumulating evidence has suggested a strong link between exposure to air pollution and public health. In particular, inhaled airborne particulate matter <2.5 μm in aerodynamic diameter (PM) can rapidly diffuse from the lungs to the systemic blood circulation and accumulate in the liver. In this study, we used a Balb/c mouse model to investigate liver injury caused by PM inhalation and the anti-inflammatory and antioxidant effects of compound essential oils (CEOs) in alleviating the extent of this injury. The results of serum biochemical and histopathological analyses showed that PM exposure induced inflammatory liver injury, meantime CEOs pretreatment attenuated PM-induced liver inflammatory injury. Western blot and qRT-PCR assays showed that PM increased secretion of cytokines, however CEOs suppressed the production of IL-6 and TNF-α. Furthermore, heme oxygenase-1(HO-1) and superoxide dismutase-1(SOD-1) expression levels showed that PM could trigger oxidative stress-mediated liver injury, whereas CEOs pretreatment might protect against PM-induced liver injury through regulation of the antioxidant system. Molecular analysis showed that the expression of TLR4, a protein which plays a key role in liver health and injury. Results showed that TLR4 was promoted by PM but inhibited by CEOs pretreatment in PM-induced inflammatory liver injury. In addition, PM-promoted secretion of cytokines by activating TLR4/MyD88 pathway, whereas CEOs might alleviate this type of liver inflammation inhibiting the activation of TLR4/MyD88 signaling pathway.
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http://dx.doi.org/10.1016/j.biopha.2018.06.010DOI Listing
September 2018

Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

Drug Des Devel Ther 2018 10;12:121-135. Epub 2018 Jan 10.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin.

Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.
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http://dx.doi.org/10.2147/DDDT.S151860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768189PMC
August 2018

Methotrexate improves perivascular adipose tissue/endothelial dysfunction via activation of AMPK/eNOS pathway.

Mol Med Rep 2017 Apr 21;15(4):2353-2359. Epub 2017 Feb 21.

Department of Gerontology, Ninth Hospital of Xi'an, Xi'an, Shaanxi 710054, P.R. China.

Adipose and endothelial dysfunction is associated with cardiovascular disease. Perivascular adipose tissue (PVAT) directly surrounds vessels and influences vessel function via a paracrine effect, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) modulates the metabolic pathway, thus, the present study hypothesized that activation of AMPK in PVAT may regulate endothelial function in pathological settings. The present study investigated the effect of methotrexate (MTX) on adipocytokine expression in PVAT with an emphasis on the regulation of endothelial function. The effects of MTX and the mechanisms involved were investigated using a relaxation assay and western blot analysis. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels. ELISA assay was used to quantify the level of TNF‑α and IL‑6. Palmitic acid (PA) stimulation induced inflammation and dysregulation of adipocytokine expression in PVAT. MTX treatment inhibited nuclear factor‑κB p65 phosphorylation and downregulated expression of pro‑inflammatory cytokines, including tumor necrosis factor‑α and interleukin-6, whereas adiponectin expression increased. MTX increased AMPK phosphorylation under basal and inflammatory conditions in PVAT, whereas knockdown of AMPK via small interfering RNA diminished its modulatory effect, indicating that MTX inhibits inflammation in an AMPK‑dependent manner. The present study prepared conditioned medium from PA‑stimulated PVAT to induce endothelial dysfunction and observed that pre‑treatment of PVAT with MTX effectively restored the loss of acetylcholine‑induced vasodilation and increased endothelial nitric oxide synthase phosphorylation in the rat aorta. The results of the present study demonstrated that MTX ameliorated inflammation-associated adipocytokine dysregulation and thus prevented endothelial dysfunction. These data provide further pharmacological evidence regarding the beneficial effects of MTX in cardiovascular diseases.
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http://dx.doi.org/10.3892/mmr.2017.6225DOI Listing
April 2017

Tetrandrine reverses epithelial-mesenchymal transition in bladder cancer by downregulating Gli-1.

Int J Oncol 2016 May 3;48(5):2035-42. Epub 2016 Mar 3.

Department of Cadiovascular Sugery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Hedgehog (Hh) signaling pathway is considered to play a crucial role in vertebrate development and carcinogenesis. Additionally, epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells become mesenchymal-appearing cells, facilitating cancer metastasis and invasion. Accumulating evidence has indicated that the Hh signaling pathway could potentiate the epithelial-mesenchymal transition (EMT). In the present study, we demonstrated that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from Stephaniae, exerts its anti-metastatic ability in bladder cancer cells by regulating GLI family zinc finger 1 (Gli-1), a key factor of Hedgehog signaling pathway. In our study, we confirmed that tetrandrine could impede migration and invasion in bladder cancer 5637 and T24 cells. Additionally, tetrandrine reverses EMT by increasing the expression of E-cadherin and reducing the N-cadherin, vimentin and Slug expression in a dose-dependent manner. Interestingly, tetrandrine also decreases mobility and reduces the expression of Gli-1 in bladder cancer cells. Moreover, we verified that tetrandrine inhibits metastasis and induces mesenchymal-epithelial transition (MET) of bladder cancer through downregulation of Gli-1, which could be partially reversed by Gli-1 overexpression. In conclusion, our findings show that tetrandrine inhibits migration and invasion, and reverses EMT of bladder cancer cells through negatively regulating Gli-1. It indicates that Gli-1 may be a potential therapeutic target of tetrandrine against bladder cancer.
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http://dx.doi.org/10.3892/ijo.2016.3415DOI Listing
May 2016

[Survival analysis of the AIDS patients under 14 years of age and receiving antiretroviral treatment in Henan province from 2003 to 2014].

Zhonghua Yu Fang Yi Xue Za Zhi 2015 Aug;49(8):700-4

Center for Disease Prevention and Control of Henan Province, Zhengzhou 450016, China; Email:

Objective: To analyze the survival status and influencing factors of the AIDS patients under 14 years of age and receiving antiretroviral treatment in Henan Province.

Methods: Database of children AIDS patients receiving ART were download from China information system for disease preventioin and control-AIDS, AIDS cases from January, 2003 to June, 2014 were selected to be analyzed. Demographic characteristics baseline laboratory inclusion criteria: F First time receive national free ART during study; aged 14 years or below; and with relatively complete baseline information and follow-up information. 1 037 cases were selected. Patient information about survival status, death, demographic characteristics, and baseline laboratory test results were analyzed. The accumulated survival rate of AIDS patients was calculated by life table method and the influencing factors were analyzed by COX proportional hazard model.

Results: A total of 1 037 AIDS children-cases ((9.52 ± 3.56) years old) which included 628 boys and 409 girls were recruited in the study, 939 cases survived 1 to 9 years from starting ART treatment and 98 cases died. Accumulated survival rate of AIDS children receiving ART from 1 year to 9 years were 96.11%, 94.17%, 92.74%, 91.28%, 90.54%, 89.47%, 88.52%, 88.52%, 86.84%, respectively. Results of multivariate analysis showed baseline count of CD4⁺ T lymphocyte (HR = 0.51, 95% CI: 0.36-0.72), duration from confirmation to the initial ART time (HR = 0.85, 95% CI: 0.75-0.97) and hemoglobin level (HR = 2.26, 95% CI: 1.09-4.70) were influence factors for survival time of AIDS children patients receiving ART.

Conclusion: Survival rate of AIDS children aged 14 years or below and receiving ART in Henan Province was relatively high. Timely surveillance of CD4⁺ T and the hemoglobin level of the AIDS patients so as to timely launch HARRT could extend survival time of AIDS patients.
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August 2015

Investigation of the impact of antinuclear antibody on the outcome of in vitro fertilization/intracytoplasmic sperm injection treatment.

Taiwan J Obstet Gynecol 2015 Dec;54(6):742-8

Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Electronic address:

Objective: The aim of this study is to investigate the influence of antinuclear antibodies (ANAs) on the pregnancy and early miscarriage rates, thereby evaluating the outcome of in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatment.

Materials And Methods: A total of 517 infertile female patients undergoing IVF/ICSI treatment (experimental group) were chosen for this study, and 186 women with normal reproductive history (control group) were designated as the control. Serum ANAs from the participants were tested using indirect immunofluorescence assay, while antiextractable nuclear antigens were tested by immune blot assay.

Results: The ANA expression in the infertile patients (39.45%) was higher than that in the control group (16.13%). A high ANA titer (≥1:320) was found only in infertile patients. ANA positivity significantly decreased the pregnancy rate and increased the early miscarriage rate after IVF/ICSI treatment. The rate of early miscarriage was higher in the high-ANA-titer individuals after IVF/ICSI treatment. Clinical pregnancy rate in anti-scl-70- and anti-PM-scl-positive individuals after IVF/ICSI treatment was lower than that in the ANA-negative individuals. Anti-Rib-p, anti-Jo-1, and anti-dsDNA were found to cause high risk of early miscarriage in pregnant women.

Conclusion: ANA positivity may not only be the cause of bad outcome during IVF/ICSI treatment, but also pose as a risk factor for IVF/ICSI treatment.
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http://dx.doi.org/10.1016/j.tjog.2015.09.001DOI Listing
December 2015

Effect of Endometrial Injury on Secretion of Endometrial Cytokines and IVF Outcomes in Women with Unexplained Subfertility.

Mediators Inflamm 2015 26;2015:757184. Epub 2015 Oct 26.

Assisted Reproduction Center of Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

In order to determine the effect of endometrial injury (EI) on in vitro fertilization (IVF) outcomes in women with unexplained subfertility and explore the relationship between EI and endometrial inflammatory cytokines, 66 women with unexplained subfertility undergoing IVF treatment were recruited. 38 patients in the EI group underwent EI in the mid-luteal phase of the cycle and 28 patients in the non-EI (NEI) group. According to the pregnancy outcome, the NEI and EI groups were divided into NEI-nonpregnant (NEI-NP), NEI-pregnant (NEI-P), EI-NP, and EI-P. All patients underwent aspiration of endometrial secretions immediately before embryo transfer. The concentrations of ten mediators were measured using Milliplex Magnetic Bead assay. The clinical pregnancy was significantly higher in the EI than in the NEI group. The concentrations of interleukin- (IL-) 6, IL-8, IL-12 (p70), IL-13, interferon- (IFN-) γ, monocyte chemotactic protein- (MCP-) 1, and vascular endothelial growth factor (VEGF) were significantly higher in the EI than the NEI group. The expression of IFN-γ and VEGF in the EI-P was significantly increased compared to the EI-NP group. These findings suggest that, in women with unexplained subfertility, endometrial injury might be a potential method to improve clinical pregnancy rates by promoting the expression of IFN-γ and VEGF.
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http://dx.doi.org/10.1155/2015/757184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637501PMC
September 2016

Combined evaluation of risk factors predicting poor ovarian responders in Chinese patients undergoing in vitro fertilization.

Gynecol Endocrinol 2016 22;32(2):124-7. Epub 2015 Oct 22.

a Reproductive Medicine Department , Beijing Obstetrics and Gynecology Hospital, Capital Medical University , Beijing , China.

This study aimed to explore the parameters associated with poor ovarian response (POR) to develop an early warning score model (EWSM) for detecting POR in Chinese women undergoing in vitro fertilization, in order to improve the outcomes. Between 2005 and 2011, we recruited 736 patients with POR after IVF and 736 individuals with normal ovarian response after IVF as controls. Clinical parameters were determined to evaluate the ovarian reserve. We then compared the clinical parameters between the POR and control groups, and performed a multivariate analysis to determine the independent factors associated with ovarian response. Receiver-operator characteristic (ROC) was used to analyze the predicted values of individual and combined risk factors. The predicted values were further tested in another cohort of 957 patients. Age, basal follicle-stimulating hormone (bFSH), antral follicle count (AFC), and FSH/luteinizing hormone (LH) ratio were identified as independent factors associated with ovarian response. The EWSM was established using a combination of these parameters. The sensitivity and specificity of the EWSM were 74.6% and 93.6%, respectively. In conclusion, combination of individual risk factors could predict POR with high specificity. The EWSM may help in the evaluation of IVF treatment at an early stage.
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http://dx.doi.org/10.3109/09513590.2015.1101442DOI Listing
December 2016

[HIV infection status among men who have sex with men in Henan, 2008-2013].

Zhonghua Liu Xing Bing Xue Za Zhi 2015 Feb;36(2):158-61

Institute for STD/AIDS Prevention and Control, Henan Provincial Center for Disease Control and Prevention, Zhengzhou 450016, China. Email:

Objective: To understand the infection status of HIV among men who have sex with men (MSM) in Henan province and provide scientific evidence for the development of AIDS prevention and control measures.

Methods: The analysis was conducted on the data about incidence of HIV infection and related risk factors among MSM in Henan from 2008 to 2013, which were obtained from AIDS reporting information system and AIDS survey in MSM.

Results: The constituent of HIV infection in MSM increased from 1.3% in 2008 to 17.1% in 2013. The HIV infection rate in MSM increased from 4.69% in 2008 to 8.33% in 2013 (trend χ² = 39.24, P < 0.001). Univariate analysis indicated that the risk factors related with HIV infection included age (χ² = 21.03, P < 0.001), education level (χ² = 31.66, P < 0.001), occupation (χ² = 14.59, P = 0.01), condom use in the last anal sex (χ² = 134.97, P < 0.001), condom use in anal sex during past 6 months (χ² = 97.15, P < 0.001), STI history (χ² = 67.21, P < 0.001) and syphilis prevalence (χ² = 163.60, P < 0.001). Multivariate analysis indicated that HIV infection related risk factors included age, STD history, syphilis prevalence and poor awareness of AIDS related knowledge.

Conclusion: The incidence of HIV infection among MSM in Henan increased rapidly, and homosexual transmission has become the major route of HIV infection. HIV infection related risk behavior is prevalent among MSM, therefore, it is necessary to take effective measures to prevent and control HIV/AIDS in MSM.
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February 2015

[Analysis on HIV suppression effect after initiating antiretroviral treatment and related factors among AIDS patients in Henan province during 2008 and 2013].

Zhonghua Yu Fang Yi Xue Za Zhi 2015 Jan;49(1):13-20

Institute for AIDS/STD Prevention and Cure, Henan Provincial Center for Disease Control and Prevention, Zhengzhou 450016, China.

Objective: To compare the HIV suppression rate after initiating antiretroviral treatment(ART) among AIDS patients at different immunological levels and to analyze the related factors.

Methods: Data on AIDS patients initially starting antiretroviral therapy during 2008 and 2013 were collected from Chinese HIV/AIDS integrated control system. All the participants were divided into early treatment group(baseline CD4(+)T cell counts between 351/µl and 500/µl) and conventional treatment group(baseline CD4(+)T cell counts ≤ 350/µl). The rates of comprehensive virologic suppression at different time nodes after the initiation of ART were analyzed accordingly. Unconditional logistic regression model was adopted to examine the factors associated with the failure of viral suppression after 6 months after initiation of ART.

Results: A total of 16 103 cases were selected, among which, 1 581 cases were early treatment group, and 14 522 cases were conventional treatment group. A total of 9 428 cases were males, 6 675 cases were females, and the sex ratio was 1.41: 1. The age was 47.2 ± 11.7, and 71.55% (11 522/16 103) of cases were married or cohabiting, 57.22% (9 214/16 103) were transmitted by blood. 81.26% (13 086/16 103) were cures in the township or village treatment institution, and 77.17% (12 426/16 103) received the ART regimen as Stavudine(D4T) or Zidovudine(AZT)+Lamivudine(3TC)+Nevirapine(NVP) or Efevirenz(EFV). After 0.5, 1, 2, 3, 4, 5 and 6 years after the initiation of ART, the rates of virologic suppression in the conventional treatment cohort were 72.6% (3 008/4 144), 73.9% (4 758/6 443), 74.1% (3 641/4 915), 74.9% (2 819/3 766), 76.1% (1 729/2 272) and 78.2% (492/629), respectively. While the rates of viral suppression in the early treatment cohort at the same time nodes were 65.5% (315/481), 65.4% (448/685), 68.8% (223/324), 66.0% (155/235), 71.4% (110/154) and 61% (30/49), respectively, and the differences between the two groups were significant (P < 0.05) except at the fourth year. Non-conditional logistic regression analysis showed that in the conventional treatment group, factors associated with low HIV suppression rate were male (OR = 1.23, 95%CI:1.07-1.42) , longer time interval from confirmed HIV infection to received ART (OR = 1.26, 95%CI:1.16-1.36) , using D4T/AZT+ DDI +NVP/EFV as initial treatment regimen (OR = 3.00, 95%CI:2.26-3.98) and nearly missing doses for 7 days at treatment of six months (OR = 1.97, 95%CI:1.22-3.18) and factors associated with high HIV suppression rate were infected through homosexual transmission route (OR = 0.57, 95%CI:0.35-0.90) and treated in the county level medical institution or above (OR = 0.61, 95%CI:0.50-0.75) . Among early treatment group, cases who received treatment at county level medical institution or above had high HIV suppression rate (OR = 0.43, 95%CI:0.23-0.80) and objects with longer time interval from confirmed HIV infection to receive ART had low HIV suppression rate (OR = 1.43, 95%CI:1.09-1.88).

Conclusion: The viral suppression efficacy among AIDS patients with different baseline immunologic levels after treatment was similarly satisfactory. AIDS cases who received ART at county level medical institution or above had better viral suppression effect and patients with longer time interval from confirmation to treatment had poor HIV suppression effect.
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January 2015

[Study on risk factors of hepatitis C virus infection among Han population in Henan province].

Zhonghua Yu Fang Yi Xue Za Zhi 2014 Nov;48(11):985-9

Institute for Prevention and Control of STD and AIDS , Henan Provincial Center for Diseases Control and Prevention, Zhengzhou 450016, China. Email:

Objective: To study the risk factors of hepatitis C Virus Infection among Han population in Henan Province, providing evidence for the development of targeted prevention and control measures.

Methods: In this 1: 1 matched case-control study, data of 134 cases and 134 controls were collected in seven hospitals from June 2013 to September 2013. Case group with the following conditions: Han nationality, first diagnosed hepatitis C in 2013, Current address and investigation belong to the same district (county), above 18 years old; with the following conditions can't into case group: not to cooperate with the investigation, late-stage Hepatitis C patients. Control group with the following conditions: Han nationality, with the matched case patients the same gender, in the same hospital for treatment , from the same district (county), the age difference ≤ 5 years old and in the same age group. With the following conditions can't into control group:not to cooperate with the investigation, diagnosed with hepatitis B, hepatitis C patients. Collect 3 ml blood samples to test anti-HCV. Single factors were analyzed with χ(2) between case and control, risk factors were analyzed with logistic regression model.

Results: The ratio about blood donation, blood transfusion, operation and acupuncture of cases were 35.1% (47/134), 27.6% (37/134), 42.5% (57/134), 12.7% (17/134), with differences compared to those of controls (2.2% (3/134), 5.2% (7/134), 21.6% (29/134), 5.2% (7/134))(χ(2) values were 47.60, 24.47, 13.42 and 4.58, all P values <0.05). Compared with those never received blood transfusion and those never donated blood, former blood receptors and blood donors had higher risk of hepatitis C infection(OR: 2.01, 95%CI:1.32-3.05; OR:2.68, 95%CI:1.85-3.88).

Results: of multiple nonconditional logistic regression analysis showed that Plasma donors and whole blood donors had higher risk of hepatitis C infection than those never donated plasma and blood (OR:76.71, 95%CI: 10.25-574.25; OR:10.23, 95%CI: 2.15-48.70).

Conclusion: Blood transfusion and abnormal blood are independent risk factors among Han population in Henan Province of hepatitis C infection. The Plasma donors, blood donors and with the increase in the times of blood transfusion, the risk of hepatitis C infection is increase.
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November 2014

[Survival effect regarding earlier initiation of antiretroviral treatment on AIDS patients].

Zhonghua Liu Xing Bing Xue Za Zhi 2014 Sep;35(9):1065-8

Henan Provincial Center for Disease Control and Prevention. Email:

Objective: To compare the survival effect of initiation of antiretroviral treatment on AIDS patients at different stages so as to explore the best time of initiation with the treatment.

Methods: Information regarding the dates of AIDS patient initially receiving the anti-retroviral therapy during 2007-2012 was collected from the Chinese HIV/AIDS Integrated Control System. According to the level of baseline immunology, all the participants were divided into earlier treatment group (baseline CD4(+) T cell counts between 350/µl and 500/µl) and conventional treatment group (baseline CD4(+) T cell counts ≤350/µl). Data was analyzed under Survival and Review methods.

Results: A total number of 16 282 cases were selected. The mortality of conventional treatment group was obviously higher than the earlier treatment group (5.78/100 person year vs. 1.64/100 person year), and the median survival time was lower than the earlier treatment group (2.07 year vs. 3.15 year). The cumulative survival rate of the 6-year conventional treatment group was lower than the earlier treatment group (77.39% vs. 92.10%, χ(2) = 156.00, P < 0.01). By means of multi-variable analysis, we found that factors as age, gender, marital status, route of transmission, schedule on initial therapy, number of symptoms at the baseline etc. in the conventional treatment group were associated with survival time of patients after the ART initiation (P < 0.05), while gender, schedule for initial therapy, number of symptoms at baseline etc. in the earlier treatment group, were associated with survival time of patients after the initiation of ART (P < 0.05).

Conclusion: Earlier initiation of antiretroviral treatment on AIDS patients could improve the survival rate and prolong the survival time.
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September 2014

[Effect of co-trimoxazole prophylaxis used for AIDS patients under anti-retroviral therapy].

Zhonghua Liu Xing Bing Xue Za Zhi 2014 Jun;35(6):689-94

Institute for AIDS/STD Prevention and Cure, Henan Provincial Center for Disease Control and Prevention, Zhengzhou 450016, China. Email:

Objective: To analyze the situation of survival among AIDS patients under cotrimoxazole prophylaxis as initial anti-retroviral therapy (ART), in Henan province during 2007-2011.

Methods: Information on AIDS patients receiving initial ART during 2007-2011 was collected from the Chinese HIV/AIDS Integrated Control System. Kaplan-Meier estimation was used to generate survival curves, and Cox proportional hazard regression model was used to determine associated factors of survival status. According to the previous CTX use before ART, the subjects were divided into 3 groups including who had never taken CTX, who had taken CTX and still taking now, who had taken CTX and not current taking.

Results: A total of 13 103 eligible AIDS patients were identified. 1 702 patients died within 6 years after the initiation of ART, with the mortality as 4.46/100 person year. Among the 455 patients who died within 3 months and 970 died within 12 months, the mortality rates were 14.15/100 person year and 7.78/100 person year, respectively. The Kaplan-Meier survival curves showed that the survival time and mortality of the patients who had taken CTX was longer AND lower than those patients who had never taken CTX when starting the ART program. Results from the log-rank test showed that the difference of two groups was statistically significant during 12 months after the ART(log-rank = 5.15, P = 0.02). After controlling for other variables, results from multivariable analysis of COX model showed that factors as age, gender, marital status, perion between confirmed diagnosis and receiving the ART, baseline CD4(+) T cells count, clinical stage, initial therapy schedule, date when starting the ART, number of symptoms at baseline, use of CTX before starting the ART and ART being skipped in the last seven days etc, were associated with the time of survival in patients after the initiation of ART. Patients who had been taking CTX at ART initiation were at lower risk of death (adjusted HR = 0.71, 95% CI:0.63-0.80; P = 0.00), compared to those who had never taken the CTX.

Conclusion: The co-trimoxazole prophylaxis program was associated with the reduced mortality among AIDS patients who were on ART in Henan province, especially during the first year.
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June 2014

Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

Mol Carcinog 2015 Sep 2;54(9):831-40. Epub 2014 Apr 2.

Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.

The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer.
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http://dx.doi.org/10.1002/mc.22154DOI Listing
September 2015

Comparison of follicular fluid amphiregulin and EGF concentrations in patients undergoing IVF with different stimulation protocols.

Endocrine 2012 Dec 8;42(3):708-16. Epub 2012 Jun 8.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, No. 49, Huayuan North Road, Haidian District, Beijing, 100191, China.

Epidermal growth factor (EGF)-like growth factors, such as amphiregulin (AR) and EGF, have emerged as mediators to propagate Luteinizing hormone (LH) stimulus for the oocyte maturation throughout the preovulatory follicle, because cumulus cells and oocytes express few or no LH receptors. This study was to compare AR and EGF concentrations in follicular fluid (FF) among four controlled ovary stimulation (COS) protocols and to investigate the relationship between FF EGF-like growth factors and COS outcomes. Ninety-five patients who underwent in vitro fertilization-embryo transfer (IVF-ET) were treated by four different COS protocols, including gonadotropin-releasing hormone agonist (GnRH-a) long protocol, GnRH-a ultra-long protocol, GnRH-a short protocol, and GnRH antagonist protocol. FF was taken on oocyte retrieval day. FF AR and EGF concentrations were measured and their correlations with COS outcomes were analyzed. FF AR concentration was significantly different from each other among four COS protocol groups (GnRH-a ultra-long protocol group, 186.12 ng/ml; GnRH-a long protocol group, 128.35 ng/ml; GnRH antagonist protocol group, 108.23 ng/ml; GnRH-a short protocol group, 77.13 ng/ml, p < 0.05). FF AR concentrations were higher in GnRH-a ultra-long and long protocol groups, while number of oocytes retrieval, available embryos, and good quality embryos in these two groups were also significantly higher than GnRH-a short protocol group and GnRH antagonist protocol group. FF AR concentration was positively correlated with available embryos, but negatively correlated with serum LH level on hCG day. FF EGF concentration had no relationship with COS parameters. Different COS protocols might have variable effects on AR synthesis. FF AR might be a good indicator to predict the number of oocytes and embryos. FF AR elevation may result in increasing the number of oocyte retrieval and embryo generation, consequently increased cumulative pregnancy rate.
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http://dx.doi.org/10.1007/s12020-012-9706-zDOI Listing
December 2012

Association of the genetic variants of luteinizing hormone, luteinizing hormone receptor and polycystic ovary syndrome.

Reprod Biol Endocrinol 2012 Apr 30;10:36. Epub 2012 Apr 30.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, Peoples Republic of China.

Background: High circulating luteinizing hormone (LH) level is a typical biochemical feature of polycystic ovary syndrome (PCOS) whose pathophysiology is still unclear. Certain mutations of LH and LH receptor (LHR) may lead to changes in bioactivity of these hormones. The aim of this study was determine the role of the LH and LHR polymorphisms in the pathogenesis of PCOS using a genetic approach.

Methods: 315 PCOS women and 212 controls were screened for the gene variants of LH G1052A and LHR rs61996318 polymorphisms by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).

Results: PCOS patients had significantly more A allele frequency of LH G1052A mutations than controls (p=0.001). Within PCOS group, carriers of LH 1052A allele had lower LH (p=0.05) and higher fasting glucose levels (p=0.04). No subjects were identified with LHR rs61996318 polymorphisms. A new LHR single nucleotide polymorphism (SNP) was found without clear association with PCOS.

Conclusions: Results suggested LH G1052A mutation might influence PCOS susceptibility and phenotypes.
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http://dx.doi.org/10.1186/1477-7827-10-36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403896PMC
April 2012

Association of TRB3 Q84R polymorphism with polycystic ovary syndrome in Chinese women.

Reprod Biol Endocrinol 2011 Apr 14;9:46. Epub 2011 Apr 14.

Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, P.R China.

Background: Tribbles 3 (TRB3) affects insulin signalling by inhibiting insulin-stimulated Akt phosphorylation and subsequent activation. A single nucleotide polymorphism located in the second extron of the human TRB3 gene is thought to be associated with insulin resistance. The latter is a core abnormality in PCOS independent of obesity. The present study was designed to clarify the relationships of TRB3 Q84R polymorphism with PCOS in a Chinese women group.

Methods: A case-control study with two groups: PCOS group (n = 336) and control group of infertility women for tubal and/or male factor (n = 116) was performed. Genotyping of the TRB3 R84 variant was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: The frequency of genotype QQ in PCOS women was significantly lower, while genotype QR and RR were significantly higher than that in control group (p < 0.05). However, the difference disappeared after adjustment for BMI. At glucose1h, glucose2h and insulin2h point, the difference between QQ individuals and R84 allele carriers in PCOS women reached statistical significance during OGTT (p < 0.05).

Conclusions: TRB3 Q84R polymorphism is associated with obesity and especially glucose metabolism and not associated with polycystic ovary syndrome because of compositional characteristics of phenotype in Chinese PCOS women.
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http://dx.doi.org/10.1186/1477-7827-9-46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094280PMC
April 2011

A surface plasmon resonance-based system to genotype human papillomavirus.

Cancer Genet Cytogenet 2010 Jul;200(2):100-5

Beijing Obstetrics and Gynecology Hospital, Capital Medical University, 251 Yao jiayuan Road, Chaoyang District, Beijing, P.R. China.

We report a novel system (W2600) that is based on the technology of surface plasmon resonance (SPR) to genotype human papillomavirus (HPV). The system permitted detection of 24 known HPV genotypes, including 16 high-risk types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 81) and 8 low-risk types (HPV 6, 11, 40, 42, 43, 44, 54, 70). Analytical performance of W2600 for HPV genotyping was evaluated by HPV DNA derived from the liquid cervical cytology specimens of 560 patients with atypical squamous cells of undetermined significance or above. In comparison with clonal sequence analysis, 358 of 560 (64%) and 355 of 560 (63%) cases were found to be positive within the 24 HPV genotypes by W2600 and sequence analysis, respectively. Concordance between these two methods was at 555 of 560 (99%) (kappa = 0.98, P < 0.001); only 5 of the 560 (1%) cases had discordant results. No cross-hybridizations were observed with the W2600 system, and the spectrum of HPV genotypes identified by W2600 included all the 16 high-risk genotypes. These data demonstrate that the SPR-based W2600 system is highly sensitive and specific in HPV genotyping and can provide an effective approach for such application in a clinical setting.
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http://dx.doi.org/10.1016/j.cancergencyto.2010.04.003DOI Listing
July 2010

Detection of human papillomavirus genotypes with liquid bead microarray in cervical lesions of northern Chinese patients.

Cancer Genet Cytogenet 2008 Apr;182(1):12-7

Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Human papillomavirus (HPV) is the main cause of cervical cancer. Blending multiplex polymerase chain reaction (PCR) amplification and multiplex hybridization to liquid bead microarray (LBMA), we detected and identified 25 common HPV genotypes using type-specific primers for HPV E6 and E7 genes in cervical lesions of northern Chinese patients. Of the 511 cervical samples, 349 (68.3%) were found to be HPV positive by HPV-LBMA. The distribution was 22 HPV positive of 100 in the control group (22%), 41 of 80 with chronic cervicitis (51%), 80 of 99 with cervical intraepithelial neoplasia (CIN) I (81%), 46 of 56 with CIN II (82%), 67 of 74 with CIN III (90%), and 93 of 102 with invasive cervical carcinoma (91%). HPV-16 was the most frequent genotype in the CIN and cervical cancer groups. The most common genotypes were HPV-16 (28%), HPV-58 (14%), HPV-52 (14%), HPV-18 (8%), and HPV-33 (7%) in the CIN group, and HPV-16 (63%), HPV-52 (9%), HPV-18 (7%), HPV-58 (7%), and HPV-33 (5%) in the cervical cancer group. HPV-LBMA found multiple genotypes in 1 of 22 control (4%), 64 of 193 CIN (33%), and 22 of 93 cervical cancer (24%). The HPV-LBMA results were compatible with those of PCR and DNA sequencing. HPV-LBMA is a simple, high-throughput method that provides useful information on viral genotype and multiple HPV infections in cervical lesions. In northern China, the most common high-risk HPV genotypes seem to be HPV types 16, 58, 52, 18, and 33. Genetic information on HPV in cervical specimens could provide particular benefits in the management of cervical lesions.
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http://dx.doi.org/10.1016/j.cancergencyto.2007.12.007DOI Listing
April 2008

Molecular diagnosis of Down's syndrome.

Chin Med J (Engl) 2003 Nov;116(11):1773-5

Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, China.

Objective: To establish a new diagnostic method for Down's syndrome using polymerase chain reaction (PCR).

Methods: DNA extracted from five healthy individuals and five Down's syndrome patients was amplified in six specific tetranucleotide repeat loci on chromosome 21 using PCR. An accurate diagnosis was made by analyzing allelic distribution at each locus.

Results: All Down's syndrome patients were identified as having at least two loci with three alleles, while none of the healthy individuals had three alleles. In addition, when two alleles were identified for a particular locus in the Down's syndrome samples, it was more likely that the intensity ratio between the two alleles was close to 2:1.

Conclusion: The molecular method can provide a fast, accurate, and economical alternation for the traditional cytogenetic diagnostic method for Down's syndrome.
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November 2003