1.Advances in mechanism of traditional Chinese medicine in inhibiting angiogenesis in ovarian cancer.
Mao-Yan TANG ; Dan-Ni DING ; Ya-Ya XIE ; Fang SHEN ; Jia LI ; Fang-Yuan LIU ; Feng-Juan HAN
China Journal of Chinese Materia Medica 2023;48(24):6572-6581
Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.
Humans
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Female
;
Medicine, Chinese Traditional
;
Vascular Endothelial Growth Factor A/metabolism*
;
Endothelial Cells/metabolism*
;
Angiogenesis
;
Angiogenesis Inhibitors/therapeutic use*
;
Ovarian Neoplasms/genetics*
;
Neovascularization, Pathologic/genetics*
2.Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH).
Ya Qi WANG ; Li Jun SHEN ; Jue Feng WAN ; Hui ZHANG ; Yan WANG ; Xian WU ; Jing Wen WANG ; Ren Jie WANG ; Yi Qun SUN ; Tong TONG ; Dan HUANG ; Lei WANG ; Wei Qi SHENG ; Xun ZHANG ; Guo Xiang CAI ; Ye XU ; San Jun CAI ; Zhen ZHANG ; Fan XIA
Chinese Journal of Gastrointestinal Surgery 2023;26(5):448-458
Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans
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Middle Aged
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Chemoradiotherapy
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Immune Checkpoint Inhibitors/therapeutic use*
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Neoadjuvant Therapy
;
Prospective Studies
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Rectal Neoplasms/pathology*
;
Thrombocytopenia/drug therapy*
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Treatment Outcome
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Adult
;
Aged
3.Diquafosol sodium combined with intense pulsed light in the treatment of meibomian gland dysfunction
Jin-Xia SHEN ; Xue-Feng LYU ; Ya-Qiong CHEN ; Dan-Dan YANG ; Xu-Juan XU
International Eye Science 2023;23(10):1714-1717
AIM:To investigate the effect of 3% diquafosol sodium eye drops combined with intense pulsed light on the treatment of meibomian gland dysfunction and the change of meibomian glands.METHODS: Prospective study. A total of 141 patients(282 eyes)who were diagnosed with meibomian gland dysfunction from January 2021 to May 2022 in our hospital were selected and they were randomly divided into the control group(73 cases, 146 eyes)and the observation group(68 cases, 136 eyes)according to random number table. The control group was given 0.3% sodium hyaluronate eye drops combined with intense pulsed light, and the observation group was treated with 3% diquafosol sodium eye drops combined with intense pulsed light. The subjective symptom score, physical sign score, non-invasive tear break-up time, tear meniscus height, lipid layer thickness, and meibomian gland density before and after the treatment were compared between the two groups at 2wk after the end of treatment.RESULTS: There were no differences in the subjective symptom score, physical sign score, non-invasive tear break-up time, tear meniscus height, lipid layer thickness, and meibomian gland density between the two groups of patients before treatment(P>0.05). After 2wk of treatment, the symptom scores and physical sign scores of patients in the two groups continued to decrease, non-invasive tear break-up time and lipid layer thickness continued to increase, and the meibomian gland density also increased. The tear meniscus height in the observation group increased, while the control group showed no significant changes. The observation group had better clinical indicators than the control group(P<0.05). No obvious complications were observed in all patients.CONCLUSION: The combination of diquafosol sodium eye drops and intense pulsed light is synergistic in the treatment of meibomian gland dysfunction, with significant therapeutic effects and improvement of meibomian gland repair, which is significantly superior to simple intense pulsed light therapy.
5.Prevalence of intestinal protozoan infections among rural children in Henan Province from 2014 to 2015
Dong-Yang ZHAO ; Tian-Tian JIANG ; Wei-Qi CHEN ; Ya-Lan ZHANG ; Yan DENG ; Bian-Li XU ; Hong-Wei ZHANG ; Wan-Shen GUO ; Xi-Meng LIN ; Peng LI ; Yu-Ling ZHAO ; Cheng-Yun YANG ; Dan QIAN ; Rui-Min ZHOU ; Ying LIU ; Su-Hua LI ; Jian-She CHEN
Chinese Journal of Schistosomiasis Control 2021;33(3):287-292
Objective To investigate the prevalence and influencing factors of intestinal protozoan infections among rural children in Henan Province. Methods A total of 104 survey sites were sampled from 35 counties (cities) in Henan Province using the stratified cluster sampling method to investigate the prevalence of intestinal protozoan infections among rural children from 2014 to 2015. The trophozoites and cysts of intestinal protozoa were identified using the iodine staining method and the physiological saline direct smear method (one detection for one stool sample). The prevalence of intestinal protozoan infections was compared among rural children with different characteristics, and the factors affecting intestinal protozoan infections among rural children were identified. Results The overall prevalence of intestinal protozoan infections was 0.60% (40/6 771) among rural children in Henan Province from 2014 to 2015. There were 7 species of intestinal protozoa identified, and there was no species-specific prevalence (χ2 = 37.732, P = 0.000). No significant differences were found in prevalence of intestinal protozoan infections among rural children in terms of gender (χ2 = 1.793, P = 0.181), age (χ2 = 1.443, P = 0.486), occupation (χ2 = 0.219, P = 0.896) or ecological region (χ2 = 1.700, P = 0.637). In addition, terrain (χ2 = 2.311, P = 0.510), economic level (χ2 = 4.322, P = 0.229), source of drinking water (χ2 = 0.731, P = 0.393), eating raw vegetables (χ2 = 1.134, P = 0.287) and deworming (χ2 = 1.089, P = 0.297) had no remarkable effects on the prevalence of intestinal protozoan infections among rural children in Henan Province; however, the prevalence of intestinal protozoan infections varied significantly among rural children living in regions with different coverage of non-harmless toilets (χ2 = 10.050, P = 0.018). Conclusion The prevalence of intestinal protozoan infections is low among rural children in Henan Province.
6.Epidemiological characteristics of malaria in Henan Province from 1950 to 2019
Wan-Shen GUO ; Dong-Yang ZHAO ; Hong-Wei ZHANG ; De-Ling LU ; Ying LIU ; Dan QIAN ; Cheng-Yun YANG ; Zhou GUAN ; Yu-Ling ZHAO ; Rui-Min ZHOU ; Su-Hua LI ; Hao WANG ; Yan DENG ; Wei-Qi CHEN ; Ya-Lan ZHANG
Chinese Journal of Schistosomiasis Control 2021;33(1):62-65
Objective To analyze the epidemiological characteristics of malaria in Henan Province from 1950 to 2019, so as to provide the scientific evidence for consolidating malaria elimination achievements in the province. Methods The epidemiological situation of malaria and demographic data in Henan Province from 1950 to 2019 were collected, and the statistical analyses were performed using a descriptive epidemiological method. The spatial temporal distribution of malaria cases was identified using the software ArcGIS version 10.3. Results During the period from 1950 through 2019, the progress of malaria elimination was divided into 4 stages in Henan Province, including the baseline-survey and key-control stage, morbidity-control and incidence-reduction stage, basic-eradication and achievement-consolidation stage and elimination stage. The spatial distribution of malaria cases shifted from south of the Huai River and the plain regions between the Yellow River and Taihang Mountain to the Huang-Huai-Hai Plain and Nanyang Basin, then was concentrated in eastern part of southern Huai River where Anopheles anthropophagus was distributed, and finally was gradually under control following malaria outbreak in Eastern Henan Plain. In addition, the species of Plasmodium changed from P. vivax, P. falciparum and P. malariae co-endemics to a single P. vivax infection, and the current co-endemics of 5 invasive malaria parasites, and the malaria vectors shifted from co-existence of Anopheles sinensis and An. anthropophagus to An. sinensis alone. Conclusions There has been a large change in the epidemiological characteristics of malaria in Henan Province from 1950 to 2019. Although malaria has been eliminated in Henan Province, the consolidation of the malaria elimination achievements remain a great challenge due to overseas imported malaria.
7.Nuclear Factor-κB Signaling Mediates Antimony-induced Astrocyte Activation.
Tao ZHANG ; Yu Dan ZHENG ; Man JIAO ; Ye ZHI ; Shen Ya XU ; Piao Yu ZHU ; Xin Yuan ZHAO ; Qi Yun WU
Biomedical and Environmental Sciences 2021;34(1):29-39
Objective:
Antimony (Sb) has recently been identified as a novel nerve poison, although the cellular and molecular mechanisms underlying its neurotoxicity remain unclear. This study aimed to assess the effects of the nuclear factor kappa B (NF-κB) signaling pathway on antimony-induced astrocyte activation.
Methods:
Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of p65. The expression of protein in brain tissue sections was detected by immunohistochemistry. The levels of mRNAs were detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and reverse transcription-polymerase chain reaction (RT-PCR).
Results:
Antimony exposure triggered astrocyte proliferation and increased the expression of two critical protein markers of reactive astrogliosis, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP), indicating that antimony induced astrocyte activation
Conclusion
Antimony activated astrocytes by activating the NF-κB signaling pathway.
Animals
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Antimony/toxicity*
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Astrocytes/metabolism*
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Cell Line, Tumor
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Cell Proliferation/drug effects*
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Glial Fibrillary Acidic Protein/metabolism*
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MAP Kinase Kinase Kinases
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Male
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Mice, Inbred ICR
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NF-kappa B/metabolism*
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Nitric Oxide Synthase Type II/metabolism*
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Rats
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Signal Transduction/drug effects*
8.Quality evaluation of Saposhnikoviae Radix based on QAMS combined with information entropy-response surface method.
Mei GUO ; Qi AN ; Ya-Jun SHEN ; Dan-Hui ZHAO ; Long GUO ; Yu-Guang ZHENG ; Dan ZHANG
China Journal of Chinese Materia Medica 2021;46(10):2537-2546
This research was used with high performance liquid chromatography(HPLC), combined with information entropy-response surface method(RSM) to investigate the ethanol concentration, extraction time, liquid-to-material ratio. Taking the content of four chromogens as evaluation indexes, the weight coefficients of each index were given, and the comprehensive score was calculated to optimize the extraction process. Then, prim-O-glucosylcimifugin was used as the reference, the relative calibration factors(RCFs) of cimifugin, 4'-O-β-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudo to prim-O-glucosylcimifugin were calculated respectively. The contents of four components in Saposhnikoviae Radix were determined by both external standard method(ESM)and quantitative analysis of multi-components by single marker(QAMS) method, and the results were compared. At last, combined with principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) to evaluate the quality of the Saposhnikoviae Radix in different production areas. The optimal extraction process parameter of the Saposhnikoviae Radix was as follows: liquid-to-material ratio is 60∶1(mL·g~(-1)), extraction time is 35 min, and ethanol concentration is 70%. The repeatability of the RCFs was perfect, and the results calculated by the QAMS were consistent with the results from the ESM. The stoichiometric results indicate that there are obvious differences in the distribution of Saposhnikoviae Radix in different production areas, and cimifugin and prim-O-glucosylcimifugin are the characteristic compounds that cause this difference. In this study, the optimal extraction process is stable and feasible, and the method of QAMS is accurate and reliable. From the perspective of four chromogens, there are differences in the quality of the Saposhnikoviae Radix in different production areas. Therefore, the established extraction process combined with the method of QAMS can be used to evaluate the quality of Saposhnikoviae Radix and provide a scientific basis for the quality control of Saposhnikoviae Radix.
Apiaceae
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Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal
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Entropy
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Plant Roots
9.Research progress in immune regulation mechanism of Polygonati Rhizoma polysaccharide
Ya-Meng ZHANG ; Yong-Shuai JING ; Dan-Shen ZHANG ; Yu-Guang ZHENG ; Lan-Fang WU
Chinese Journal of Pharmacology and Toxicology 2021;35(10):779-780
Polygonati Rhizoma is the dry rhizome of Liliaceae plants Polygonatum kingianum coil ethemsl, Polygona?tum sibiricum Redoute and Polygonatum cyrtonem Hua. It tastes sweet and has a flat nature. It belongs to the spleen, lung and kidney channels. Polygonati Rhizoma contains a variety of chemical components, including polysaccharides, alkaloids, steroidal saponins, lignans, phytosterols, and so on. Polygonati Rhizoma polysaccharide (PSP) is one of the main bioactive components of Polygonati Rhizoma. It is widely used. It has the effects of enhancing immunity, anti-inflammatory, anti-virus and regulating blood lipid. In recent years, the immunomodulatory function of PSP has been paid more and more attention by researchers. PSP can play an immunomodulatory role through a variety of mecha?nisms. (1) Effects of PSP on innate immunity. ① Macrophages have a strong ability to phagocytize and clear foreign bodies. When polysaccharides bind to macrophage specific membrane receptors, the immune response will be officially activated. RAW264.7 cells can be activated by PSP MR and TLR4 mediated signal pathway to improve the pinocytosis and phagocytosis of RAW264.7 cells. ② Natural killer cell (NK cell) is a very important immune cell in the body. It is a non-specific immune killer cell naturally existing in the body. It has the dual functions of immune regulation and cytotoxic?ity. It was found that the signal pathway mediated by PSP CR3 and TRL2 may play a major role in the stimulation of NK cells. (2) Effects of PSP on adaptive immune response. ① Lymphocytes can be divided into two forms: T cells and B cells due to different differentiation and maturation sites. T lymphocytes are the general name of thymus dependent lym?phocytes. B lymphocytes differentiate and mature from animal bone marrow cells and exert their humoral immune func?tion by secreting different antibodies. It was found that PSP could activate T/B lymphocytes and increase the ratio of CD4+/CD8+in lymph cells to promote the regulation of immune system.②Thymus and spleen index refers to the level of body immunity through the development of immune organs and the functional status of immune cells. The higher the index of thymus and spleen, the higher the immune activity. A large number of studies have found that PSP can improve immune activity by promoting the proliferation of spleen lymphocytes and regulating organ index, so as to increase the weight and index of thymus and spleen induced by CY. ③ Antibody is a glycoprotein secreted by B cells after antigen stimulation and a series of proliferation and differentiation into plasma cells. Antibody production level is one of the main indicators of nonspecific immune function. PSP can not only improve the serum antibody level of mice by regulating the phagocytosis of mouse macrophages and the level of serum hemolysin, but also enhance the concentration of IL-2 secreted by spleen lymphocytes in vitro to increase the level of antibody response, and then improve the humoral immune function of the body. (3) Effect of PSP on cytokines. ① A large number of experiments have proved that PSP has a significant effect on promoting the production of interleukin (IL). PSP can combine with specific receptors on the surface of immune cells to activate various intracellular signal transduction pathways, enhance the secretion of cytokines such as IL-2, IL-4, IL-6 and IL-10 by spleen lymphocytes in vitro, make them directly kill target cells and regulate the immune function of the body at the molecular level. ② Interferon (IFN) is a special protein or glycoprotein produced by human or animal cells in response to various stimuli. It plays an important role in anti-virus, immune regulation and cell proliferation control. It was found that PSP could increase IFN-γsecreted by T cells and NK cells, activate macrophages to regulate immune function. ③ Tumor necrosis factor (TNF) is mainly produced by activated macrophages, NK cells and activated T cells. It is a cytokine with important biological activity in antitumor immune response.④ Tumor necrosis factor (TNF) is mainly produced by activated macrophages, NK cells and activated T cells. It is a cytokine with important biological activity in antitumor immune response. PSP can promote the proliferation and phagocytic activity of macro?phage RAW264.7 to reduce its apoptosis rate. By increasing the secretion of TNF-α, PSP can promote the dissociation between NF-κВprotein and IκВp65 protein after phosphorylation, so as to start the expression and transcription of related immune genes. In conclusion, PSP can improve immunity and has a good application prospect in the development of immunomodulatory drugs.
10.Relationship between Polymorphism in ALOX5, ALOX5AP and Susceptibility to Myeloid Leukemia.
Fen MEI ; Yan-Fei WANG ; Dan YANG ; Rong-Xia ZUO ; Tao SHEN ; Tong-Hua YANG ; Ya-Lian SA
Journal of Experimental Hematology 2020;28(1):40-50
OBJECTIVE:
To investigate the correlation of single nucleotide polymorphisms (SNP) in arachidonate 5-lipoxygenase gene (ALOX5) rs2029253, rs2228064 and rs2228065 sites, 5-lipoxygenase activating protein gene (ALOX5AP) rs10507391, rs4769874 sites with the risk for genesis of adult myeloid leukemia.
METHODS:
By the approval from the hospital ethics committee and the informed consent of participants. 150 patients with myeloid leukemia (ML) as ML group and 134 healthy people as the control group were selected. The genomic DNA was extracted from the samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with directly sequencing, PCR-amplified products were applied to test the polymorphism of 5 sites in ALOX5 and ALOX5AP gene.
RESULTS:
A allele frequencies of ALOX5 gene rs2029253 site in the ML group and the control group were 43.0% and 34.3%, respectively. And the G allele frequencies in the ML group and the control group were 57.0% and 65.7%, respectively. The genotype distributions of AA, AG and GG in ALOX5 gene rs2029253 site in the ML group were 32.2%, 21.5% and 46.3% respectively. That in the control group were 15.7%, 37.3% and 47.0% respectively. The genotype AA and A allele frequency of ALOX5 gene rs2029253 site were linked with the increased risk of myeloid leukemia (OR=2.26, 95% CI: 1.43-4.56, P<0.05; OR=1.44, 95% CI: 1.02-2.03, P<0.05). And the genotype AG and allele G reduced the susceptibility to myeloid leukemia (OR=0.46, 95% CI: 0.27-0.78, P<0.01; OR=0.69, 95% CI: 0.50-0.98, P<0.05), however, the polymorphisms of ALOX5 gene rs2228064 and rs2228065 site not correlated with the risk of myeloid leukemia (P>0.05). The A allele frequency of ALOX5AP gene rs10507391 site in the ML group and the control group were 30.7% and 36.2% respectirely. The genotype distribution rates of AA, AT and TT in ALOX5AP gene rs10507391 site in the ML group was 1.3%, 58.7% and 40.0% respectively, that in the control group were 9.7%, 53.0% and 37.3% respectively. The genotype AA of ALOX5AP gene rs10507391 site correlated with the decreased risk of myeloid leukemia (OR=0.13, 95% CI: 0.03-0.57, P<0.05), but the polymorphism of ALOX5AP gene rs4769874 site not correlated with the risk of myeloid leukemia (P>0.05).
CONCLUSION
The genotype AA, AG and allele A, G of ALOX5 rs2029253, as well as ALOX5AP rs10507391 may be correlate with the susceptibility to myeloid leukemia.

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