1.Effect of down-regulation of FABP5 on radiation damage of human keratinocytes
Hongdan GUAN ; Rong ZHENG ; Bingjie GUAN ; Yuping LIN ; Bisi WANG ; Benhua XU ; Jianyuan SONG
Chinese Journal of Radiological Medicine and Protection 2023;43(1):8-14
Objective:To investigate the effects of down-regulation of FABP5 (fatty acid binding protein 5) on radiation damage of skin cells, and explore underlying mechanism.Methods:A lentiviral vector with down-regulated FABP5 was constructed to infect human immortalized keratinocytes (HaCaT) cells, and the transfection efficiency was examined. The HaCaT cells were divided into blank control group, FABP5 down-regulation group (FABP5), radiation group (IR), and FABP5 down-regulation combined with radiation group (FABP5+ IR). After 6 MV X-ray radiation, cell proliferation viability was measured by CCK-8 assay, cell migration was detected by scratch assay, apoptosis was analyzed by flow cytometry, radiosensitivity was evaluated by cloning formation assay, and the cellular protein expressions of PARP1, γ-H2AX, AKT and p-AKT were detected by Western blot.Results:FABP5 was successfully knocked-down in both RNA level ( t=25.14, P<0.05) and protein level ( t=20.06, P<0.05). The down-regulation of FABP5 decreased the abilities of cells proliferation ( t=3.55, 5.88, 3.18, P<0.05) and migration ( t=15.44, P<0.05), but increased cell resistance to irradiation with a radiosensitization ratio of 0.782. The apoptosis rate of FABP5+ IR group was significantly lower than IR group (22.05±6.71)% vs. (9.82±1.45)%, t=3.08, P<0.05. The protein levels of PARP1 and γ-H2AX in FABP5+ IR group were also lower than those in the IR group 0.04±0.04, 0.11±0.06, 0.26±0.11, 0.22±0.07, 0.21±0.10, 0.52±0.22, 0.57±0.06, 0.43±0.02( t=2.83, 3.07, 4.50, 5.33, P<0.05), while the protein level of p-Akt in FABP5+ IR group was higher than that in IR group ( t=-16.24—3.02, P<0.05). Conclusions:Down-regulation of FABP5 inhibited cell proliferation and migration, increased radioresistance, and reduced radiation-induced apoptosis and DNA damage of skin cells probably through PI3K/AKT signaling pathway.
2.Endovascular treatment of ischemic moyamoya disease
Bingjie ZHENG ; Jinbiao YAO ; Huaizhang SHI
International Journal of Cerebrovascular Diseases 2023;31(4):271-274
Moyamoya disease is a relatively rare cerebrovascular disease. Extracranial and intracranial vascular bypass is the first choice for moyamoya disease. However, due to the risk of complications and symptoms recurrence after surgery, there is still some controversy about surgical treatment. In recent years, with the development of minimally invasive interventional technology, the endovascular treatment of atherosclerotic ischemic cerebrovascular disease has been widely carried out in the world. Some doctors are also beginning to try endovascular treatment of ischemic moyamoya disease, but its efficacy and safety are still unclear. This article reviews the endovascular treatment of ischemic moyamoya disease.
3.The value of ouantitative parameters of magnetic resonance imaging in predicting the efficacy of chimeric antigen receptor T-cell therapy for children and adolescents with mature aggressive B-cell non-Hodgkin lymphoma
Bingjie ZHENG ; Yuxia LI ; Xiaocao CHEN ; Wenjuan XU ; Yang LI ; Bo HU ; Yonghong ZHANG ; Chunmiao XU
Chinese Journal of Applied Clinical Pediatrics 2023;38(8):595-599
Objective:To investigate the value of quantitative parameters of magnetic resonance imaging (MRI) in predicting the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy for children and adolescents with mature aggressive B-cell non-Hodgkin lymphoma (NHL).Methods:It was a retrospective multicenter study.Clinical data of 44 children and adolescents diagnosed with mature aggressive B-cell NHL between January 2016 and January 2023 in Henan Cancer Hospital, Beijing Gaobo Boren Hospital, and the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed.Patients were divided into complete response (CR) group and non-CR group based on the international criteria for the diagnosis of pediatric NHL.Quantitative parameters of MRI, including T2 signal intensity, the minimal apparent diffusion coefficient (ADCmin), maximal ADC (ADCmax), and the mean ADC (ADCmean) were measured before and within 2 weeks after CAR-T infusion.The correlation between the above parameters and the achievement of CR was analyzed.The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement among observers in measuring quantitative parameters of MRI.Differences between groups were analyzed using the independent sample t-test.Factors influencing CR were identified through the binary Logistic regression analysis, and a prediction model was established.Model performance was evaluated by plotting receiver operating characteristic (ROC) curves. Results:Significant differences were observed between the CR group and non-CR group in T2 signal intensity before CAR-T infusion (267±152 vs.364±160, P=0.048), and ADCmin (0.94±0.38 vs.0.53±0.28, P<0.05), ADCmax (1.73±0.69 vs.0.84±0.43, P<0.05), ADCmean (1.28±0.48 vs.0.67±0.33, P<0.05), and T2 signal intensity within 2 weeks after CAR-T infusion (198±139 vs.345±168, P=0.004). A univariate prediction model was created by introducing the above quantitative parameters.The area under the curve (AUC), specificity, sensitivity, and accuracy of T2 signal intensity before CAR-T infusion in predicting the efficacy on children and adolescents with mature aggressive B-cell NHL were 0.800, 84.0%, 57.9%, and 72.7%, respectively.The AUC, specificity, sensitivity, and accuracy of ADCmax within 2 weeks of CAR-T infusion were 0.958, 88.0%, 78.9%, and 84.1%, respectively.The AUC, specificity, sensitivity, and accuracy of T2 signal intensity within 2 weeks of CAR-T infusion were 0.869, 84.0%, 68.4%, and 77.3%, respectively. Conclusions:Quantitative parameters of MRI, including ADC values and T2 signal intensity, are of great significance in the early prediction of CAR-T therapy efficacy on children and adolescents with mature aggressive B-cell NHL.Among these parameters, ADCmax presents the strongest predictive performance and serves as a valuable indicator for predicting a complete response with CAR-T treatment.
4.Progress on the relationship between consumption of added sugar and incidence of gynecologic cancer
Gang ZHENG ; Yifan WEI ; Qijun ZHAO ; Bingjie ZOU ; Qijun WU ; Yuhong ZHAO
Journal of Public Health and Preventive Medicine 2023;34(4):114-118
Globally, gynecological malignancies are common types of female cancer and the main cause of cancer death among women. Cervical cancer, endometrial cancer and ovarian cancer, which are the main types of gynecological cancers, pose a significant threat to women's health worldwide. Studies have shown that diet plays an important role in the occurrence and development of gynecological cancers such as cervical cancer, endometrial cancer, and ovarian cancer, for which added sugar may be an influencing factor due to its food source characteristic and related biological effect. However, this paper reviewed the research progress on the relationship between consumption of added sugar and gynecological cancers such as endometrial cancer, ovarian cancer and cervical cancer, with a view to providing a reference for the active prevention of gynecological cancer.
5.CT texture analysis for predicting pseudoprogression in metastatic clear cell renal cell carcinoma during PD-1 inhibitor therapy
Bingjie ZHENG ; Wenjuan XU ; Lingdi ZHAO ; Chunmiao XU ; Hailiang LI
Chinese Journal of Internal Medicine 2023;62(9):1114-1120
Objective:To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy.Methods:A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis.Results:A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included“original_ngtdm_Strength”(0.49 vs. -0.61, P=0.006), “wavelet-HLH_glszm_ZonePercentage”(0.67 vs. -0.22, P=0.024),“wavelet-LHL_ngtdm_Strength”(1.20 vs. -0.51, P=0.002), “wavelet-HLL_gldm_LargeDependenceEmphasis”(-0.84 vs. 0.19, P=0.002), “wavelet-HLH_glcm_Id” (-0.30 vs. 0.43, P=0.037),“wavelet- HLH_glrlm_RunPercentage”(0.45 vs. -0.01, P=0.032),“wavelet-LHH_firstorder_Skewness”(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95% CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95% CI 0.817-0.997) according to ROC curve analysis. Conclusions:Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.
6.Iso-Kikuchi syndrome: report of two cases
Bingjie ZHENG ; Xiao LIN ; Jia CHEN ; Qiufang QIAN
Chinese Journal of Dermatology 2023;56(4):313-315
To report 2 cases of Iso-Kikuchi syndrome, both of which were congenital. Case 1, a 7-month-old female infant, visited the hospital due to abnormalities in the nail plate of the left index finger for 7 months; case 2, a 3-year-old male child, also visited the hospital due to abnormalities in the nail plate of the left index finger for 3 years. The 2 patients both presented with 2 tiny, independent nail plates on both sides of the nail bed of the left index finger, instead of normal nail plates. Based on their clinical features, the 2 patients were diagnosed with Iso-Kikuchi syndrome (congenital onychodysplasia of the index finger). The mother of case 1 had a history of progesterone use to prevent miscarriage during pregnancy, the mothers of the two patients both suffered from hypothyroidism and continued to receive thyroid hormone replacement therapy during pregnancy, and the mother of case 2 had a history of gestational diabetes. It is still unclear whether these comorbidities and drugs are directly related to the occurrence of Iso-Kikuchi syndrome.
7.Comparison of Radiological Tumor Response Based on iRECIST and RECIST 1.1 in Metastatic Clear-Cell Renal Cell Carcinoma Patients Treated with Programmed Cell Death-1 Inhibitor Therapy
Bingjie ZHENG ; Ji Hoon SHIN ; Hailiang LI ; Yanqiong CHEN ; Yuan GUO ; Meiyun WANG
Korean Journal of Radiology 2021;22(3):366-375
Objective:
To evaluate the radiological tumor response patterns and compare the response assessments based on immunebased therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1 in metastatic clear-cell renal cell carcinoma (mccRCC) patients treated with programmed cell death-1 (PD-1) inhibitors.
Materials and Methods:
All mccRCC patients treated with PD-1 inhibitors at Henan Cancer Hospital, China, between January 2018 and April 2019, were retrospectively studied. A total of 30 mccRCC patients (20 males and 10 females; mean age, 55.6 years; age range, 37–79 years) were analyzed. The target lesions were quantified on consecutive CT scans during therapy using iRECIST and RECIST 1.1. The tumor growth rate was calculated before and after therapy initiation. The response patterns were analyzed, and the differences in tumor response assessments of the two criteria were compared. The intra- and inter-observer variabilities of iRECIST and RECIST 1.1 were also analyzed.
Results:
The objective response rate throughout therapy was 50% (95% confidence interval [CI]: 32.1–67.9) based on iRECIST and 30% (95% CI: 13.6–46.4) based on RECIST 1.1. The time-to-progression (TTP) based on iRECIST was longer than that based on RECIST 1.1 (median TTP: not reached vs. 170 days, p = 0.04). iRECIST and RECIST 1.1 were discordant in 8 cases, which were evaluated as immune-unconfirmed PD based on iRECIST and PD based on RECIST 1.1. Six patients (20%, 6/30) had pseudoprogression based on iRECIST, of which four demonstrated early pseudoprogression and two had delayed pseudoprogression.Significant differences in the tumor response assessments based on the two criteria were observed (p < 0.001). No patients demonstrated hyperprogression during the study period.
Conclusion
Our study confirmed that the iRECIST criteria are more capable of capturing immune-related atypical responses during immunotherapy, whereas conventional RECIST 1.1 may underestimate the benefit of PD-1 inhibitors. Pseudoprogression is not rare in mccRCC patients during PD-1 inhibitor therapy, and it may last for more than the recommended maximum of 8 weeks, indicating a limitation of the current strategy for immune response monitoring.
8.LncRNA LEF1-AS1 regulates proliferation, apoptosis, migration and invasion of cutaneous squamous cell carcinoma cells by targeting miR-612: an in vitro experimental study
Yunpeng ZHENG ; Xuyang LI ; Bingjie CAI ; Dongqin LI ; Guangwen YIN
Chinese Journal of Dermatology 2020;53(6):415-423
Objective:To evaluate the effects of long non-coding RNA (lncRNA) LEF1-AS1 on proliferation, apoptosis, migration and invasion of cutaneous squamous cell carcinoma cells, and to explore their mechanisms.Methods:Cutaneous squamous cell carcinoma SCC13 cells were divided into si-LEF1-AS1 group transfected with lncRNA LEF1-AS1 interference oligonucleotides (si-LEF1-AS1) , si-NC group transfected with lncRNA LEF1-AS1 nonsense oligonucleotides (si-NC) , miR-612 group transfected with miR-612-overexpressing oligonucleotides, miR-NC group transfected with miR-612 nonsense oligonucleotides (miR-NC) , si-LEF1-AS1+anti-miR-612 group transfected with si-LEF1-AS1 and oligonucleotides against miR-612, and si-LEF1-AS1+anti-miR-NC group transfected with si-LEF1-AS1 and miR-612 nonsense oligonucleotides. Quantitative reverse transcription (qRT) -PCR was performed to determine the relative expression of miR-612 in SCC13 cells, cell counting kit-8 (CCK8) assay to evaluate cellular proliferative activity, flow cytometry to detect cell apoptosis, Transwell assay to assess migratory and invasive abilities of SCC13 cells, and Western blot analysis to determine protein expression of cyclin-dependent kinase 1 (cyclinD1) , cyclinD1 inhibitor p21, Bcl-2 family protein (Bcl-2) , Bcl-2 related X protein (Bax) , matrix metalloproteinase 2 (MMP-2) and MMP-9. The online bioinformatics database LncBase predicted v.2 was employed to predict the complementary sequence between lncRNA LEF1-AS1 and miR-612, and luciferase reporter gene plasmids were constructed by using the complementary/non-complementary sequence, which were co-transfected with miR-612-overexpressing oligonucleotides (miR-612 overexpression group) or miR-NC (overexpression control group) into SCC13 cells in order to verify the binding ability of lncRNA LEF1-AS1 to miR-612. Statistical analysis was carried out by using t test for comparison between two groups, one-way analysis of variance for comparison among multiple groups, and least significant difference (LSD) - t test for multiple comparisons. Results:Compared with the miR-NC group, miR-612 group showed significantly decreased cellular proliferative ability, number of migratory cells and invasive cells (all P < 0.05) , but a significantly increased apoptosis rate ( P < 0.05) . The relative expression of miR-612 ( F = 150.78, P < 0.001) , cellular proliferative activity at 24, 48, 72 hours (all P < 0.05) , apoptosis rate and number of migratory and invasive cells (all P < 0.05) significantly differed among the si-LEF1-AS1 group, si-NC group, si-LEF1-AS1+anti-miR-612 group and si-LEF1-AS1+anti-miR-NC group. Compared with the si-NC group, the si-LEF1-AS1 group showed significantly increased expression of miR-612 and apoptosis rates, but significantly decreased cellular proliferative activity at 48, 72 hours, and number of migratory and invasive cells (all P < 0.05) ; compared with the si-LEF1-AS1+anti-miR-NC group, the si-LEF1-AS1+anti-miR-612 group showed significantly decreased expression of miR-612 and apoptosis rates, but significantly increased cellular proliferative activity at 48, 72 hours, and number of migratory and invasive cells (all P < 0.05) . Western blot analysis showed that the relative protein expression of cyclinD1, p21, Bcl-2, Bax, MMP-2 and MMP-9 significantly differed among the si-LEF1-AS1 group, si-NC group, si-LEF1-AS1+anti-miR-612 group and si-LEF1-AS1+anti-miR-NC group (all P < 0.001) ; compared with the si-NC group, the si-LEF1-AS1 group showed significantly increased protein expression of cyclinD1, Bcl-2, MMP-2 and MMP-9, but significantly decreased protein expression of p21 and Bax (all P < 0.05) ; compared with the si-LEF1-AS1+anti-miR-NC group, the si-LEF1-AS1+anti-miR-612 group showed significantly increased protein expression of cyclinD1, Bcl-2, MMP-2 and MMP-9, but significantly decreased protein expression of p21 and Bax (all P < 0.05) . After co-transfection with complementary sequences, the fluorescence activity was significantly lower in the miR-612 overexpression group than in the overexpression control group ( t = 21.19, P < 0.001) ; after co-transfection with non-complementary sequences, no significant difference was observed in the fluorescence activity between the miR-612 overexpression group and overexpression control group ( t = 0.28, P = 0.78) . Conclusion:lncRNA LEF1-AS1 regulates the proliferation, apoptosis, migration and invasion of cutaneous squamous cell carcinoma cells, likely by targeting miR-612.
9.lncRNA DLX6-AS1 regulates the proliferation, migration and invasion of a cutaneous squamous cell carcinoma cell line A431 by targeting miR-16-5p/NUCKS1
Yunpeng ZHENG ; Bingjie CAI ; Xuyang LI ; Dongqin LI ; Guangwen YIN
Chinese Journal of Dermatology 2020;53(8):607-615
Objective:To investigate effects of long non-coding growth stasis specific protein 6 antisense RNA1 (lncRNA DLX6-AS1) on the proliferation, migration and invasion of a cutaneous squamous cell carcinoma cell line A431, and to explore the underlying mechanisms.Methods:A dual-luciferase reporter system was used to verify the targeting relationship between lncRNA DLX6-AS1 and miR-16-5p, as well as between miR-16-5p and nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) mRNA. Cultured A431 cells were divided into several groups: si-DLX6-AS1 group and DLX6-AS1-NC group transfected with lncRNA DLX6-AS1 inhibitor and its negative control respectively; anti-miR-16-5p group and anti-miR-NC group transfected with miR-16-5p inhibitor and its negative control respectively; si-NUCKS1 group and NUCKS1-NC group transfected with NUCKS1 inhibitor and its negative control respectively; si-DLX6-AS1+ anti-miR-16-5p group transfected with lncRNA DLX6-AS1 inhibitor followed by miR-16-5p inhibitor, and si-DLX6-AS1+ anti-miR-NC group transfected with lncRNA DLX6-AS1 inhibitor followed by anti-miR-NC; si-DLX6-AS1+ anti-miR-16-5p+ si-NUCKS1 group transfected with lncRNA DLX6-AS1 inhibitor, miR-16-5p inhibitor and NUCKS1 inhibitor, and si-DLX6-AS1+ anti-miR-16-5p+ NUCKS1-NC group transfected with lncRNA DLX6-AS1 inhibitor, miR-16-5p inhibitor and NUCKS1-NC. After the above treatment, real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to measure the mRNA expression of lncRNA DLX6-AS1, miR-16-5p and NUCKS1 in A431 cells, Western blot analysis to determine the protein expression of NUCKS1, Cyclin D1 antibody, matrix metalloproteinase (MMP) 2 and MMP9, cell counting kit-8 (CCK8) assay to detect cell survival rate, and Transwell assay to evaluate cell migratory and invasive abilities. Two-independent-sample t test was used for comparisons between two groups. Results:Dual-luciferase reporter assay showed targeted binding of lncRNA DLX6-AS1 to miR-16-5p, as well as of miR-16-5p to NUCKS1. Compared with the DLX6-AS1-NC group, the si-DLX6-AS1 group showed significantly increased miR-16-5p expression in A431 cells (3.01 ± 0.31 vs. 1.02 ± 0.10, t = 18.33, P < 0.001) , but significantly decreased protein expression of NUCKS1, Cyclin D1, MMP2 and MMP9 (all P < 0.05) , and significantly decreased cell survival rate and numbers of migratory and invasive cells (all P < 0.05) . Compared with the NUCKS1-NC group, the si-NUCKS1 group showed significantly decreased protein expression of NUCKS1, Cyclin D1, MMP2 and MMP9 in A431 cells (all P < 0.05) , and significantly decreased cell survival rate and numbers of migratory and invasive cells (all P < 0.05) . After inhibition of lncRNA DLX6-AS1 expression, the si-DLX6-AS1+ anti-miR-16-5p group showed significantly decreased miR-16-5p expression in A431 cells (0.34 ± 0.04) compared with the si-DLX6-AS1+ anti-miR-NC group (1.00 ± 0.12, t = 15.65, P < 0.05) , but significantly increased protein expression of Cyclin D1, MMP2 and MMP9, cell survival rate and numbers of migratory and invasive cells compared with the si-DLX6-AS1+ anti-miR-NC group (all P < 0.05) . After inhibition of lncRNA DLX6-AS1 expression and knockdown of miR-16-5p, the si-DLX6-AS1+ anti-miR-16-5p+ si-NUCKS1 group showed significantly decreased protein expression of NUCKS1, Cyclin D1, MMP2 and MMP9 in A431 cells, as well as cell survival rate and numbers of migratory and invasive cells, compared with the si-DLX6-AS1+ anti-miR-16-5p+ NUCKS1-NC group (all P < 0.05) . Conclusion:lncRNA DLX6-AS1 can regulate the proliferation, migration and invasion of A431 cells by targeting miR-16-5p/NUCKS1, suggesting that lncRNA DLX6-AS1 may be a potential molecular target for the treatment of cutaneous squamous cell carcinoma.
10.Prevalence and Molecular Characterization of Echinococcus granulosus Sensu Stricto in Northern Xinjiang, China
Baoping GUO ; Zhuangzhi ZHANG ; Xueting ZHENG ; Yongzhong GUO ; Gang GUO ; Li ZHAO ; Ren CAI ; Bingjie WANG ; Mei YANG ; Xi SHOU ; Wenbao ZHANG ; Bin JIA
The Korean Journal of Parasitology 2019;57(2):153-159
Echinococcus granulosus is an important zoonotic parasite globally causing cystic echinococcosis (CE) in humans and animals. In this study, prevalence of CE and variation of cox1 gene sequence were analyzed with isolates E. granulosus collected from different areas in northern Xinjiang, China. The survey showed that 3.5% of sheep and 4.1% of cattle were infected with CE. Fragment of cox1 was amplified from all the positive sheep and cattle samples by PCR. In addition, 26 positive samples across the 4 areas were included. The isolates were all E. granulosus sensu stricto (s.s.) containing 15 haplotypes (Hap1-15), and clustered into 2 genotypes, G1 (90.1%, 91/101) and G3 (9.9%, 10/101). Hap1 was the most common haplotype (48.5%, 49/101). Hap9 were found in humans samples, indicating that sheep and cattle reservoir human CE. It is indicate that E. granulosus may impact on control of CE in livestock and humans in the region.
Animals
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Cattle
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China
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Cross-Sectional Studies
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Echinococcosis
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Echinococcus granulosus
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Echinococcus
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Genotype
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Haplotypes
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Humans
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Livestock
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Parasites
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Polymerase Chain Reaction
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Prevalence
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Sheep


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