Neural tube defect (NTD) is a complex and serious birth defect in the central nervous system.The etiology of NTD is multifactorial,involving the combined action of both genetic and environmental factors.Maternal nutrition is a significant environmental factor in NTD etiology,including vitamin B,folic acid,choline,and so on.Inositol,a substance of vitamin B,is closely related to embryonic development and NTD.Studies have found out that inositol supplement can prevent folic acid-resistant NTD and the key genes in its metabolic pathways play an important role in NTD occurrence.Therefore,this article reviews the inositol metabolic pathways and the relationship between its key genes and NTD,providing references for the depth study of NTD pathogenesis and prevention.

Objective To detect the genomic copy number variations(CNVs) of mice embryonic neural tissue with neural tube defects (NTDs) induced by methotrexate (MTX),and investigate the molecular genetic mechanisms between folic acid metabolism disorders and NTDs pathogenesis.Methods C57BL/6J NTD mice model was induced by MTX on gestational day 7.5,and the maternal serum and NTD embryonic neural tissues were collected;the array-comparative genomic hybridization(array-CGH) assay was utilized to analyze the whole genomic CNVs in NTD embryonic neural tissues;reverse transcription polymerase chain reaction(RT-PCR) was used to confirm the positive results;the maternal serum concentrations of folic acid and related metabolites and dihydrofolate reductase (DHFR) activity were detected by liquid chromatography-tandem mass spectrometry and enzymatic methods,respectively.Results ArrayCGH and RT-PCR results showed the 3 high confidence CNVs on XqE3,XqA1.1-qA2 and XqA1.1 in the NTD embryonic neural tissues.The NTD maternal serum concentrations of 5-methyltetrahydrofolate,5-formyltetrahydrofolic acid,S-adenosyl methionine and DHFR activity were reduced significantly compared with the control group,and there were statistical differences(all P ＜0.05).Conclusions There are obvious CNVs in embryonic neural tissue of NTD mice induced by MTX and folic acid dysmetabolism might cause mice embryonic neural tube developmental disorders through CNVs.

Objective To conduct a prospective phase Ⅱ clinical study to explore the distribution of CYP2D6 gene polymorphism in Chinese population and its relationship with the metabolism of tamoxifen in early-stage hormonal receptor-positive breast cancer. Methods CYP2D6 genotype was tested by Sanger sequencing using the ABI 3500 Genetic Analyzer. Plasma concentrations of tamoxifen and endoxifen were measured using the HPLC-MS/MS(API 2000)assay. We downloaded the data of CYP2D6 allele from the CPIP database. Results In Chi-nese patients,the most common alleles were CYP2D6*1,*2,and *10;the predominant diplotypes were *1/*10 (38.3%)and*10/*10(18.8%). The distribution of metabolic phenotype,plasma concentration of endoxifen,and endoxifen:tamoxifen plasma concentration ratio were inconsistent between the normal metabolic phenotype(EM) and the intermediate phenotype(IM)under different CYP2D6 activity prediction criteria.The differences in the ratios and endoxifen plasma concentrations were statistically significant between the three groups by cluster analysis. Conclusions The CYP2D6 genotype distribution in Chinese population is different from that in the Western popu-lation. There is considerable variation of serum endoxifen concentration in Chinese breast cancer patients possess-ing the phenotype previously known as the intermediate active metabolizers of CYP2D6. Therefore,in the current era of precision medicine,the standard CYP2D6 genotype-phenotype classification system cannot properly stratify the Chinese population with different levels of endoxifen plasma concentration.

Objective To compare the efficacy and safety of everolimus combined with endocrine therapy and fulvestrant in patients with estrogen receptor-positive advanced breast cancer progressed after endocrine thera-py. Methods Ninety-three breast cancer patients were selected from January 2014 to February 2017. The primary end points were progression-free survival and clinical benefit rate and the secondary end points was tolerability. Re-sults The progression-free survival in fulvestrant group was slightly higher than that in the everolimus group(13.4 months vs 12.2 months,P = 0.297). The clinical benefit rates were 46.15% and 31.71% in fulvestrant group and everolimus group,respectively. Patients treated with fewer than 2 lines and endocrine resistant patients benefited more from fulvestrant but without statistical difference. The main adverse events related to everolimus were stomati-tis,with a prevalence rate of about 26% and a localized pneumonia with a prevalence rate of about 10%. The main adverse reaction of fulvestrant was the injection site reaction. Conclusions The efficacy of everolimus in combina-tion with endocrine therapy is not superior to that of fulvestrant for the treatment of advanced breast cancer pro-gressed after endocrine therapy. After weighing the clinical benefits and quality of life,fulvestrant may be better for patients treated with fewer than 2 lines and endocrine resistance.

Objective:To evaluate the image quality (IQ) of 18F-fluorodeoxyglucose (FDG) PET/CT imaging and identify its influenfial factors in diabetes mellitus (DM) and non-DM patients with coronary artery disease (CAD). Methods:A total of 196 consecutive CAD patients (174 males, 22 females, 68 DM; age: (57±10) years) in Beijing Anzhen Hospital between June 2016 and February 2018 were retrospectively analyzed. All patients underwent 18F-FDG myocardial PET/CT imaging. The standardized fasting+ oral glucose loading (OGL) and intravenously injection of insulin protocol was performed. According to the FDG uptake by myocardium, background activity in blood and other visceral organ nearby the heart, the IQ was visually evaluated and scored by 0-4. Zero-two was considered as good IQ, 3-4 was regarded as poor IQ. Patients were divided into three groups: group 1 (non-DM+ good IQ), group 2 (DM+ good IQ), group 3 (DM+ poor IQ). Factors which may affect IQ were analyzed, which including OGL, the injection dose of insulin, fasting blood glucose (FBG), peak blood glucose (PBG), blood glucose (BG) level at 18F-FDG injection (BG injnection), BG increasing rate ((PBG-FBG)/FBG, %), and BG decreasing rate ((PBG-BG injection)/PBG, %). One-way analysis of variance, Spearman correlation analysis and logistic regression analysis were used for data analysis. Results:There were significant differences ( F values: 13.074-38.371, all P<0.05) of FBG, PBG, OGL, BG decreasing rate and the injection dose of insulin among group 1 ( n=132, 67.3%), group 2 ( n=53, 27.1%), group 3 ( n=11, 5.6%). All those parameters, except for OGL, were positively correlated with FDG PET/CT IQ ( r s values: 0.142-0.262, all P<0.05). OGL was negatively correlated with IQ ( r s=-0.324, P<0.05). Logistic regression analysis showed that FBG (odds ratio ( OR)=0.687, 95% CI: 0.633-0.746), PBG( OR=0.786, 95% CI: 0.746~0.829), BG injection( OR=0.631, 95% CI: 0.595-0.716), OGL( OR=0.897, 95% CI: 0.873-0.922), the injection dose of insulin( OR=0.680, 95% CI: 0.618-0.748) were predictive factors (all P<0.01) for good IQ in all patients. For DM patients, OGL was the only predictive factor for good IQ( OR =0.940, 95% CI: 0.904-0.960; P<0.01). Conclusions:FBG, PBG, BG injection, OGL, the injection dose of insulin can predict IQ for all patients with CAD. For DM patients with CAD, OGL is the only predictive factor for good IQ. A good IQ of 18F-FDG PET/CT could be obtained in majority of CAD patients, with the standardized fasting + OGL and intravenously injection of insulin protocol and adjust according to the personal status, and prevent the hypoglycemia from happening.