1.Expression of Serum Vaspin and SFRP5 in Children with Idiopathic Nanosomia and Their Diagnostic Value
Yingshuang WU ; Xiangdong XUE ; Zhihui DU ; Lihong WANG ; Yuanbo CHENG ; Xiaoqing NIU ; Dawei WANG
Journal of Modern Laboratory Medicine 2024;39(1):95-99
Objective To explore the expression level of visceral adipose tissue-derived serine protease inhibitor(Vaspin)and secreted frizzled-related protein5(SFRP5)in the serum of children with idiopathic short stature(ISS)and its diagnostic value.Methods 70 children with ISS diagnosed in the First Hospital of Zhangjiakou from December 2021 to February 2023 were selected as the disease group,while 72 healthy volunteer children who underwent physical examination were collected as the control group.Immunoluminescence was applied to detect the expression level of VASPIN,Enzyme-linked immunosorbent assay(ELISA)was applied to detect the expression level of SFRP5 the clinical data of children in two groups were analyzed.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum Vaspin and SFRP5 for ISS,multivariate Logistic regression was used to analyze the influencing factors of ISS.Results Compared with the control group,the serum Vaspin level in the disease group was obviously increased(2.89±0.92 ng/ml vs 1.81±0.42 ng/ml),while the SFRP5 level was obviously reduced(10.22±2.84 pg/ml vs 13.21±3.53 pg/ml),the differences were statistically significant(t=9.040,5.552,all P<0.05).The weight,height,body mass index(BMI)and proportion of sexual development stage II~V of children in the disease group were obviously lower than those in the control group,and the differences were statistically significant(t=7.687,6.330,5.559,7.024,all P<0.05).The area under ROC curve showed that the AUC of Vaspin and SFRP5 and their combined detection in the diagnosis of ISS were 0.768,0.849 and 0.925,respectively,the combined diagnosis efficacy of Vaspin and SFRP5 was better than that of serum Vaspin and SFRP5 alone(Z =3.829,P<0.001;Z =2.141,P=0.032).Multivariate Logistic regression analysis showed that BMI(OR=0.508,95%CI:0.260~0.991),Vaspin(OR=3.458,95%CI:1.125~10.631)and SFRP5(OR=0.378,95%CI:0.153~0.935)were the influencing factors for ISS(all P<0.05).Conclusion The expression level of Vaspin in the serum of children with ISS is obviously increased,while the expression level of SFRP5 is obviously reduced.The two are influencing factors of ISS,and the combined detection of their expression levels has certain value in the diagnosis of ISS.
2.Single-cell RNA sequencing and the pathogenesis of intervertebral disc degeneration
Haotian CHENG ; Xiaofeng ZHAO ; Xiangdong LU ; Yibo ZHAO ; Zhifeng FAN ; Detai QI ; Xiaonan WANG ; Runtian ZHOU ; Xinjie JIN ; Bin ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(1):93-99
BACKGROUND:Intervertebral disc degeneration is clinically considered to be the main cause of low back pain,but due to the unclear pathogenesis of intervertebral disc degeneration,there is still a lack of effective means to delay the progression of the disease.Single-cell RNA sequencing technology can amplify and sequence mRNA at the single-cell level,reveal the gene expression intensity of a single cell,discover different cell subsets in tissues according to the heterogeneity of cells,study the pathogenesis of intervertebral disc degeneration at the molecular level,and provide a new theoretical basis for its early diagnosis and treatment. OBJECTIVE:To introduce the basic principles of single-cell RNA sequencing technology and review the research progress of single-cell RNA sequencing technology in intervertebral disc degeneration in recent years. METHODS:A computer was used to search PubMed,Web of Science,CNKI and WanFang databases for the literature published from 2012 to 2022.Key words were"single-cell RNA sequencing,intervertebral disc degeneration,sequencing Technology"in Chinese and English.Duplicate,poor-quality and irrelevant articles were excluded;a total of 70 articles were eventually included. RESULTS AND CONCLUSION:(1)We identified new cell subsets such as homeostatic chondrocytes,hypertrophy chondrocyte-like nucleus pulposus cells and fibrous nucleus pulposus cells,identified the marker genes and transcription factors of these cell subsets,and described the functions,differentiation paths and cell fate of these cell subsets during the development and progression of intervertebral disc degeneration,and proposed the concept of progenitor nucleus pulposus cells.A cell subpopulation with progenitor nucleus pulposus cells properties was identified and its effectiveness in treating intervertebral disc degeneration was verified in mice.(2)Fibro chondrocyte-like annulus fibrosus cells and annulus fibrosus stem cells with both cartilage and fiber properties were identified,and a new type of composite hydrogel was prepared by combining fibrous cartilage inducers silk fibroin and hyaluronic acid in vitro.Experiments in mice demonstrated that this hydrogel could repair both annulus fibrosus tissue and cartilage matrix,and was remarkably effective in the treatment of intervertebral disc degeneration.(3)Regulatory chondrocytes were found in endplate cartilage.Two distinct fates in the progression of intervertebral disc degeneration were analyzed and the differential genes in the two fates were identified.Intercellular communication analysis indicated that regulatory chondrocytes interact with endothelial cells to promote angiogenesis.(4)Immune cells such as macrophages,T cells,myeloid progenitor cells and neutrophils were identified in the degenerated intervertebral disc tissues,demonstrating the existence of immune response during intervertebral disc degeneration.It was found that apolipoprotein induced the polarization of macrophages M1 and M2 subtypes,and this polarization process affected the activity of progenitor nucleus pulposus cells by amplifying the inflammatory response through the MIF signaling pathway.
3.Effect of macrophages polarization on proliferation,migration and osteogenic differentiation of periodontal ligament stem cells
Kepeng LI ; Zhenguo SHEN ; Xiangdong LIU ; Tiantian CHENG ; Yuanyin WANG
Acta Universitatis Medicinalis Anhui 2024;59(8):1392-1398
Objective To explore the effects of different phenotypes macrophages(Mφs)on the proliferation,mi-gration and osteogenic differentiation of periodontal ligament stem cells(PDLSCs).Methods PDLSCs were isola-ted and cultured by tissue block method.Tohoku Hospital Pediatrics-1(THP-1)cell line was stimulated to activate into unpolarized Mφs(M0),then induced to polarize into type Ⅰ Mφs(M1)and type Ⅱ Mφs(M2).Quantitative real-time PCR(qPCR)detected the inflammatory factors tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,IL-6,IL-10 and transforming growth factor-β(TGF-β)mRNA expression level.After collecting culture superna-tants with different phenotypes,PDLSCs were stimulated,native control(NC)group did not receive the culture su-pernatant of Mφs.The effects of PDLSCs proliferation were assessed via Methylthiazolyldiphenyl-tetrazolium bro-mide(MTT)assay,while scratch assays were employed to evaluate their migration.Western blot was utilized to analyze the protein expression of Runt-related transcription factor 2(RUNX2)and alkaline phosphatase(ALP).Additionally,Alizarin Red staining was performed to investigate the deposition of calcified nodules in PDLSCs.Re-sults qPCR showed the relative expression of TNF-α,IL-1 β and IL-6 in M1 Mφs were higher than those in M0 and M2 Mφs(P<0.05),and the relative expression of IL-10 and TGF-β in M2 Mφs were higher than those in M0 and M1 Mφs(P<0.05);Western blot showed the expression of RUNX2 and ALP proteins in PDLSCs in M0 and M2 groups was higher than those in the NC group(P<0.05),Alizarin Red staining showed increased calcified nodule deposition in PDLSCs in M0,M1 and M2 groups compared to the NC group;MTT assay showed the prolifer-ation of PDLSCs in the M0 and M1 groups was suppressed compared to the NC group(P<0.05);and scratch ex-periment showed the migratory capacity of PDLSCs in the M1 and M2 groups was stronger than that in the NC group.Conclusion M0 and M1 Mφs inhibit PDLSCs proliferation,M1 and M2 Mφs promote PDLSCs migration,and all types of Mφs promote osteogenic differentiation of PDLSCs.
4.Five-year survival analysis of gastric cancer from population-based cancer registration data in Zhejiang province, China
Huizhang LI ; Hongting ZHU ; Yaoyao CHEN ; Rongshou ZHENG ; Guangfu JIN ; Lingbin DU ; Xiangdong CHENG
Chinese Journal of Oncology 2024;46(9):862-870
Objective:To analyze epidemiology of gastric cancer five-year survival distribution in Zhejiang population-based cancer registration.Methods:The follow-up data of registrated gastric cancer cases diagnosed from 2008 to 2019 in 22 national cancer registry areas of Zhejiang Province were collected and divided into three diagnostic periods: 2008-2011, 2012-2015 and 2016-2019 to calculate five-year observed survival rates (OSRs), five-year relative survival rates (RSRs) and five-year age-standardized relative survival rates (ARSRs). The distribution of population characteristics (including gender, urban/rural, age group and occupation) and clinical characteristics (including the highest diagnostic institution, sub-site, pathological type and degree of differentiation) of gastric cancer survival rates in each period were analysed.Results:51 663 new cases of gastric cancer in 2008-2019 in the cancer registration area of Zhejiang Province were included in the analysis, and the ARSR of gastric cancer in 2008-2011, 2012-2015 and 2016-2019 showed an increasing trend (39.2%, 41.3% and 44.7%, respectively). In 2016-2019, the ARSR was similar across gender and urban and rural areas (44.4% for men and 45.7% for women; 44.9% in urban areas and 44.2% in rural areas); Among people with different occupations, the ARSR was highest among business and service workers (55.3%), the agriculture, forestry, animal husbandry and fisheries, water conservancy production workers and domestic workers were lower (41.5% and 43.2%, respectively). The highest diagnostic institution was the provincial hospital with a higher gastric cancer survival rate (47.0%) than the municipal (43.4%) and district (43.6%) levels. The ARSR for gastric cancer was relatively high in the lesser curvature (59.7%), pylorus (50.4%), antrum (49.3%), and greater curvature (48.7%), and lowest in cardia (38.9%). Among the major pathological types, adenocarcinoma (NOS) had an ARSR of 48.1%, mucinous adenocarcinoma 41.3%, imprinted cell carcinoma 39.4%, and squamous carcinoma 33.4%. The ARSR for highly differentiated, moderately differentiated, poorly differentiated and undifferentiated gastric cancers were 80.6%, 57.9%, 43.2% and 36.8%, respectively.Conclusion:The 5-year survival rate of gastric cancer in Zhejiang Province is high and on the rise, with similar survival rates in different genders, urban and rural areas, and significant differences in the survival rates of gastric cancer patients with different occupational groups, highest diagnostic institutions, tumour sub-sites, pathological types and differentiation degrees.
5.Five-year survival analysis of gastric cancer from population-based cancer registration data in Zhejiang province, China
Huizhang LI ; Hongting ZHU ; Yaoyao CHEN ; Rongshou ZHENG ; Guangfu JIN ; Lingbin DU ; Xiangdong CHENG
Chinese Journal of Oncology 2024;46(9):862-870
Objective:To analyze epidemiology of gastric cancer five-year survival distribution in Zhejiang population-based cancer registration.Methods:The follow-up data of registrated gastric cancer cases diagnosed from 2008 to 2019 in 22 national cancer registry areas of Zhejiang Province were collected and divided into three diagnostic periods: 2008-2011, 2012-2015 and 2016-2019 to calculate five-year observed survival rates (OSRs), five-year relative survival rates (RSRs) and five-year age-standardized relative survival rates (ARSRs). The distribution of population characteristics (including gender, urban/rural, age group and occupation) and clinical characteristics (including the highest diagnostic institution, sub-site, pathological type and degree of differentiation) of gastric cancer survival rates in each period were analysed.Results:51 663 new cases of gastric cancer in 2008-2019 in the cancer registration area of Zhejiang Province were included in the analysis, and the ARSR of gastric cancer in 2008-2011, 2012-2015 and 2016-2019 showed an increasing trend (39.2%, 41.3% and 44.7%, respectively). In 2016-2019, the ARSR was similar across gender and urban and rural areas (44.4% for men and 45.7% for women; 44.9% in urban areas and 44.2% in rural areas); Among people with different occupations, the ARSR was highest among business and service workers (55.3%), the agriculture, forestry, animal husbandry and fisheries, water conservancy production workers and domestic workers were lower (41.5% and 43.2%, respectively). The highest diagnostic institution was the provincial hospital with a higher gastric cancer survival rate (47.0%) than the municipal (43.4%) and district (43.6%) levels. The ARSR for gastric cancer was relatively high in the lesser curvature (59.7%), pylorus (50.4%), antrum (49.3%), and greater curvature (48.7%), and lowest in cardia (38.9%). Among the major pathological types, adenocarcinoma (NOS) had an ARSR of 48.1%, mucinous adenocarcinoma 41.3%, imprinted cell carcinoma 39.4%, and squamous carcinoma 33.4%. The ARSR for highly differentiated, moderately differentiated, poorly differentiated and undifferentiated gastric cancers were 80.6%, 57.9%, 43.2% and 36.8%, respectively.Conclusion:The 5-year survival rate of gastric cancer in Zhejiang Province is high and on the rise, with similar survival rates in different genders, urban and rural areas, and significant differences in the survival rates of gastric cancer patients with different occupational groups, highest diagnostic institutions, tumour sub-sites, pathological types and differentiation degrees.
6.Influencing Factors for Compliance of Gastroscopy and Colonoscopy in Gastrointestinal Cancer Screening Program
Weiyan YU ; Xue LI ; Juan ZHU ; Xiaoliang WANG ; Shoujun LI ; Lingbin DU ; Xiangdong CHENG
China Cancer 2024;33(11):937-951
[Purpose]To analyze the compliance rates and influencing factors for gastroscopy and colonoscopy in gastrointestinal cancer screening,and to provide evidence and management recom-mendations for gastrointestinal cancer screening programs.[Methods]The study was based on the joint gastrointestinal cancer screening program conducted in Fenghua District of Ningbo City in 2023.The target population underwent risk assessments,following which high-risk individuals were mobilized for gastroscopy and colonoscopy screenings.The x2 test was used to compare the positive rates of gastrointestinal cancer risk assessments and the compliance rates of clinical screenings among populations with different characteristics.Multivariable Logistic regression models were applied to analyze the factors associated with compliance rates of clinical gastroscopy and colonoscopy screenings among high-risk individuals.[Results]A total of 48 587 individuals were included in the analysis,with an average age of(63.95±7.48)years old.Among them,39.45%(19 166 individuals)were male.The positive rates of risk assessment for upper gastrointestinal cancer and colorectal cancer were 39.00%(18 949 individuals)and 16.02%(7 782 individuals),respectively.The compliance rates for gastroscopy and colonoscopy were 59.51%(11 227/18 949)and 50.85%(3 957/7 782),respectively.Multivariable Logistic regression analysis revealed that unmarried in-dividuals and those with an assessment interval of more than 14 d had lower compliance with gas-troscopy(both P<0.05).High-risk individuals for upper gastrointestinal cancer with BMI≥24 kg/m2,gastrointestinal symptoms,history of upper gastrointestinal diseases,family history of cancers,history of gastroscopy,lower intake of fresh vegetables and fruits,and higher intake of processed meats had higher compliance with gastroscopy(all P<0.05).High educational levels and an assess-ment interval of more than 14 d were associated with lower compliance with colonoscopy(both P<0.05).Among individuals at high risk for colorectal cancer,those with gastrointestinal symptoms,history of upper gastrointestinal diseases,higher intake of processed meats and fried or grilled foods,and a positive risk assessment for upper gastrointestinal cancer had higher compliance with colonoscopy(all P<0.05).[Conclusion]Participants in the joint gastrointestinal cancer screening program exhibit high compliance with both gastroscopy and colonoscopy.Compliance with gas-troscopy and colonoscopy is associated with individual lifestyle,health conditions,disease history,medical history,and family history of cancers.
7.Analysis of discipline construction of tumor radiotherapy in non-public hospitals in Zhejiang province
Xiaozhong CHEN ; Yaoxin LIU ; Chunyang LU ; Yongting YANG ; Ji ZHU ; Tao ZHU ; Xiangdong CHENG
Chinese Journal of Radiation Oncology 2023;32(10):881-885
Objective:To investigate the radiotherapy discipline construction and existing problems in non-public hospitals in Zhejiang province and put forward suggestions for improvement.Methods:In 2022, on-site inspection and investigation were carried out in 14 non-public hospitals in Zhejiang province, including equipment configuration and source, discipline setting, personnel qualification and professional experience, academic leaders and admission of patients, etc. Results:For 14 non-public hospitals in Zhejiang province, 19 treatment equipment, 15 positioning equipment and 77 quality control equipment were equipped, and a total of 249 radiotherapy practitioners were employed. A total of 4 224 patients were admitted throught 2022.Conclusion:Multiple problems exist in non-public radiotherapy hospitals in Zhejiang province, such as unscientific discipline setting, fewer professionals, lack of personnel training, unclear management mode, unqualified qualification of partial radiotherapy doctors, and insufficient refinement of clinical quality management, which need to be further improved.
8.Influencing factors for lymph node metastasis and prognosis in early gastric cancer
Jingyang HE ; Enze LI ; Pengcheng YU ; Yanqiang ZHANG ; Can HU ; Xiangdong CHENG ; Zhiyuan XU
Chinese Journal of Digestive Surgery 2023;22(9):1093-1099
Objective:To investigate the influencing factors for lymph node metastasis and prognosis in early gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 011 patients with early gastric cancer who were admitted to the Zhejiang Cancer Hospital from January 2010 to December 2019 were collected. There were 561 males and 450 females, aged (58±11)years. All patients underwent radical resection of gastric cancer and the lymph node metastasis of each group was identified according to the pathological examination on patients' surgical specimens. Observation indicators: (1) lymph node metastasis in early gastric cancer; (2) influencing factors for lymph node metastasis in early gastric cancer; (3) influencing factors for prognosis in early gastric cancer. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed using the non‐parameter rank sum test. Univariate analysis was conducted using the Log-Rank test and Logistic regression model, and multivariate analysis was conducted using the Logistic stepwise regression model and COX step-wise regression model. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-Rank test was used for survival analysis. Results:(1) Lymph node metastasis in early gastric cancer. The lymph node metastasis rate of 1 011 patients with early gastric cancer was 23.640%(239/1 011), in which the lymph node metastasis rate of patients with T1a stage gastric cancer was 11.883%(53/446), and the lymph node metastasis rate of patients with T1b stage gastric cancer was 32.920%(186/565). There were 239 patients with lymph node metastasis mainly concentrated in the first station, including 7 cases with No.1 lymph node metastasis, 11 cases with No.2 lymph node metastasis, 135 cases with No.3 lymph node metastasis, 59 cases with No.4 lymph node metastasis, 39 cases with No.5 lymph node metastasis, 91 cases with No.6 lymph node metastasis, 6 cases with No.7 lymph node metastasis, 8 cases with No.8 lymph node metastasis, 8 cases with No.9 lymph node metastasis and 6 cases with No.10 lymph node metastasis. Multiple lymph node metastases may exist in the same patient. For lymph node metastasis in different tumor sites, there were 4 cases, 2 cases and 1 case of lymph node metastasis in the No.2, 3 and 5 lymph node in patients with upper gastric cancer. There were 3 cases, 7 cases, 36 cases, 15 cases, 3 cases and 5 cases of lymph node metastasis in the No.1, 2, 3, 4, 5 and 6 lymph node in patients with middle gastric cancer. There were 4 cases, 97 cases, 44 cases, 35 cases and 86 cases of lymph node metastasis in the No.1, 3, 4, 5 and 6 lymph node in patients with lower gastric cancer. (2) Influencing factors for lymph node metastasis in early gastric cancer. Results of multivariate analysis showed that tumor diameter, tumor location, degree of tumor invasion, vascular thrombus, degree of tumor differentiation were independent factors influencing lymph node metastasis in early gastric cancer ( odds ratio=1.80, 1.49, 2.65, 5.76, 0.60, 95% confidence interval as 1.29-2.50, 1.11-2.00, 1.81-3.88, 3.87-8.59, 0.48-0.76, P<0.05). (3) Influencing factors for prognosis in early gastric cancer. All 1 011 patients were followed up for 43(range, 0-135)months, and the 3-year overall survival rate was 97.32%. Results of multivariate analysis showed that age >60 years and lymph node metastasis were independent risk factors influencing prognosis in early gastric cancer ( hazard ratio=9.50, 2.20, 95% confidence interval as 3.31-27.29, 1.00-4.87, P<0.05). Results of further analysis showed that the 3-year overall survival rate was 99.37% and 94.66% in patient with age >60 years and ≤60 years, respectively, showing a significant difference between them ( χ2=25.33, P<0.05). The 3-year overall survival rate was 95.42% and 97.92% in patients with and without lymph node metastasis, respectively, showing a significant difference between them ( χ2=5.69, P<0.05). Conclusions:The lymph node metastasis rate of early gastric cancer can reach 23.640%. Tumor diameter, tumor location, degree of tumor invasion, vascular thrombus, degree of tumor differentia-tion are independent factors influencing lymph node metastasis in early gastric cancer, age >60 years and lymph node metastasis are independent risk factors influencing prognosis.
9.Experiences in use of kissing pancreatojejunostomy in 267 cases of pancreatoduodenectomy
Jia WU ; Xiangdong CHENG ; Yuhua ZHANG ; Yian DU ; Zhiyuan XU ; Litao YANG ; Fang HAN
Chinese Journal of General Surgery 2022;37(5):344-347
Objective:To investigate feasibility, efficiency and safety of kissing pancreatojejunostomy after pancreatoduodenectomy.Methods:From Jan 2006 to Sep 2020, the clinical data of 267 patients undergoing pancreatoduodenectomy and kissing pancreatojejunostomy were retrospectively analyzed.Results:Grade B postoperative pancreatic fistula (POPF) occurred in 6.37%, Grade C POPF in 2.25% of patients. There was no mortality within 30 days postoperatively as to pancreatic fistula, by cut-off of pancreatic duct diameter at 3mm, there was no significant difference between two subgroups (15/140 vs. 8/127, P=0.20). also, when grouped by texture of the pancreas, no there was significant difference (20/194 vs. 3/73, P=0.11). Conclusions:Kissing pancreatojejunostomy is feasible and easy to perform. It also does not increase the POPF rate when applied to the pancreatojejunostomy with thin pancreatic duct and soft texture.
10.Genetic variant analysis and prenatal diagnosis for Chinese pedigrees affected with cblC methylmalonic acidemia.
Lei LI ; Yanjie XIA ; Shuang HU ; Guiying CHENG ; Xiaofan ZHU ; Yang LIU ; Xiangdong KONG
Chinese Journal of Medical Genetics 2022;39(10):1058-1064
OBJECTIVE:
To detect variants of the MMACHC gene among 110 ethnic Han Chinese pedigrees affected with metabolic deficiency methylmalonic acidemia (MMA) of cobalamin C (cblC).
METHODS:
Peripheral blood samples were collected from the probands and their parents. Following DNA extraction, the coding regions of the MMACHC gene were subjected to PCR amplification, Sanger sequencing and quantitative PCR assaying. For 48 pedigrees, chorionic villus samples were taken for prenatal genetic diagnosis.
RESULTS:
Thirty five types of variants were detected among the 110 pedigrees, which included missense, nonsense, frameshifting, splicing variants and exonic deletions. Most variants have occurred in exons 4 (73.18%). The detection rate for c.609G>A (p.Trp203Ter) variant was the highest (33.64%), followed by c.658_660delAAG (12.27%), c.567dupT (9.09%) and c.80A>G (6.82%). Two variants, namely c.57_58insT (p.Gly20Trpfs*14) and c.505_506delAT (p.Ile169Argfs*12), were unreported previously and both were of frameshifting types. For the 48 pedigrees undergoing prenatal diagnosis, 14 fetuses were found to be normal, 24 have carried heterozygous variants, the remaining 10 have carried compound heterozygous or homozygous variants.
CONCLUSION
The discovery of the two novel variants has expanded the spectrum of the MMACHC gene variants among ethnic Han population. Above finding has provide a basis for the prenatal diagnosis and genetic counseling for the affected pedigrees.
Amino Acid Metabolism, Inborn Errors/genetics*
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China
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DNA
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Female
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Humans
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Mutation
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Oxidoreductases/genetics*
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Pedigree
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Pregnancy
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Prenatal Diagnosis
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Vitamin B 12/genetics*


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