OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) and karyotyping in the prenatal diagnosis for carriers of balanced translocations. METHODS: Clinical records of 135 amniocentesis samples of balanced translocation carriers undergoing simultaneous CNV-seq and karyotyping were analyzed. Chromosomal aberrations were defined as those can definitely lead to birth defects definitely, which included chromosomal numerical abnormality, large deletion/duplication and pathogenic copy number variations (pCNVs). RESULTS: The detection rates for karyotyping and CNV-seq were 4.44% (6/135) and 5.93% (8/135) respectively, and the latter had a detection rate of 1.48(2/135) higher than the former. A total of 68 fetal chromosomal translocations were detected by karyotying analysis. CONCLUSION For couples carrying a balanced translocation, simultaneous CNV-seq and karyotyping is conducive to the detection of fetal chromosomal abnormalities and genetic counseling.
Chromosome Aberrations ; Chromosome Disorders/genetics* ; DNA Copy Number Variations ; Female ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic

Objective:To investigate the iodine nutrition level of pregnant women in Shanxi Province, and to provide basis for guiding pregnant women to supplement iodine scientifically.Methods:From 2016 to 2018, 40, 80 and 118 counties were selected in Shanxi Province. In each county, 5 townships were selected according to the east, west, south, north and middle orientation, 20 pregnant women were selected from each township. Urine and salt samples of pregnant women were collected, and urinary iodine and salt iodine contents were determined, respectively.Results:From 2016 to 2018, 3 590, 7 907, and 11 750 salt samples were collected from pregnant women's homes. The medians salt iodine were 23.80, 23.70, 23.25 mg/kg, and the qualified iodized salt consumption rates were 91.06% (3 269/3 590), 90.06% (7 121/7 907), 92.21% (10 835/11 750), and the coverage rate of iodized salts were 97.72% (3 508/3 590), 97.00% (7 670/7 907), 98.53% (11 577/11 750), and the qualified rate of iodized salts was 93.19% (3 269/3 508), 92.84% (7 121/7 670), 93.59% (10 835/11 577), respectively. There were statistically significant differences in the median salt iodine and qualified iodized salt consumption rate among pregnant women in different years ( H = 99.915, χ 2 = 27.988, P < 0.05). Totally 3 902, 7 892 and 11 745 urine samples of pregnant women were tested, and the medians (quartiles) urinary iodine were 174.20 (114.00, 251.08), 180.70 (117.13, 258.58) and 179.40 (115.90, 249.00) μg/L, respectively. There was statistically significant difference in the median urinary iodine among pregnant women in different years ( H = 12.368, P < 0.05). From 2016 to 2018, counties with appropriate levels of iodine accounted for 70.00% (28/40), 73.75% (59/80) and 70.34% (83/118), respectively. The medians (quartiles) urinary iodine levels of pregnant women in the early, middle and late stages of pregnancy ( n = 2 225, 5 727, 3 793) in 2018 were 177.62 (117.28, 257.23), 178.21 (117.40, 248.40) and 172.70 (112.98, 245.70) μg/L, respectively, and there was statistical by significant difference in urinary iodine levels among pregnant women in different pregnancy periods ( H = 11.077, P < 0.05). Conclusions:From 2016 to 2018, the iodine nutrition level of pregnant women in Shanxi Province is generally in an appropriate state, iodine deficiency or more than appropriate still exists in some areas. We should continue to carry out monitoring work, and focus on strengthening health education for pregnant women, and guide them to supplement iodine scientifically and accurately.

Objective:To study the risk factors for ipsilateral severe hearing impairment in patients with hemifacial spasm (HFS) after microvascular decompression (MVD).Methods:MVD was performed in 3700 patients with HFS, admitted to our hospital from October 2007 to August 2020; according to the existence of ipsilateral severe hearing impairment, these patients were divided into severe hearing impairment group and non-severe hearing impairment group. The clinical data of these patients were compared. Multivariate linear regression analysis was used to determine the independent influencing factors for ipsilateral severe hearing impairment.Results:Forty-five patients (1.2%) had ipsilateral severe hearing impairment after MVD; no one got recovery of hearing impairment during the follow-up period (0.6-11.8 years, 6.3 years in average). As compared with those in the non-severe hearing impairment group, patients in the severe hearing impairment group had significantly older age, significantly higher percentages of male patients, and patients with left HFS, hypertension, and diabetes mellitus, statistically higher percentage of patients having small posterior fossa volume, arachnoid thickening and adhesion, and vertebral artery compression, significantly lower percentage of patients with anterior inferior cerebellar artery compression, significantly higher percentage of patients with arteriosclerosis of offending arteries and difficult decompression ( P<0.05). Multivariate linear regression analysis revealed that hypertension, vertebral artery compression, arteriosclerosis of offending artery and difficult decompression were independent risk factors for severe hearing impairment in patients with HFS after MVD. Conclusion:It's difficult to get recovery for severe hearing impairment in patients with HFS after MVD; this complication is much common in patients with hypertension, vertebral artery compression, arteriosclerosis of offending artery or difficult decompression.

OBJECTIVE: To explore the prevalence and characteristics of chromosomal abnormalities in abortuses during early pregnancy with single nucleotide polymorphism microarray (SNP-array). METHODS: For 520 abortuses, copy number variations (CNVs) in chorionic villi were analyzed with SNP-array. RESULTS: In 510 (98.1%) of the samples, the analysis was successful. Among these, 57.6% (294/510) of the samples were found to harbor clinically significant chromosomal abnormalities. 38.8% of the samples (198/510) had a normal result. 2.4% (12/510) of the samples harbored benign CNVs, and 1.2% (6/510) harbored variants of uncertain significance (VOUS). Aneuploidies, polyploidies, pathogenic CNVs and uniparental disomies (UPD) had accounted for 75.2% (221/294), 13.9% (41/294), 8.2% (24/294), and 2.7% (8/294) of the samples, respectively. 45,XO was the most common finding, which was followed by trisomy 16 and trisomy 22. 69,XXY was the most common polyploidy. CONCLUSION Chromosomal abnormalities are the main cause for early miscarriage, among which aneuploidies are most common. The prevalence of aneuploidies is significantly increased among women over 35. SNP-array analysis has the advantage of high success rate, high resolution and great accuracy, but the clinical significance of microdeletions/microduplications found by SNP-array can be difficult for interpretation.
Chorionic Villi ; Chromosome Aberrations ; Chromosome Disorders ; DNA Copy Number Variations ; Female ; Genetic Testing ; Humans ; Karyotyping ; Polymorphism, Single Nucleotide ; Pregnancy

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Objective: To observe and evaluate the clinical efficacy of laparoscopic abdominoperineal intersphincteric resection com-bined with ileostomy for the treatment of ultra-low rectal cancer. Methods: Clinicopathologic data of 74 patients undergoing laparo-scopic radical resection for ultra-low rectal cancer at Coloproctology Hospital of Chengdu from January 2015 to June 2017 were retro-spectively analyzed. In total, 43 patients underwent laparoscopic abdominoperineal intersphincteric resection combined with ileosto-my (ISR group), and 31 patients underwent laparoscopic low anterior resection combined with ileostomy (LAR group). The periopera-tive condition, radical resection of tumor, and postoperative anal function were compared between the two groups. Results: There were no significant differences in blood loss, postoperative hospital stay, and postoperative complications between the groups (all P>0.05). The mean operative time was (306.6 ± 25.1) minutes in the ISR group and (239.7 ± 26.4) minutes in the LAR group (P=0.010). There were no significant differences in pT and pN between the groups (all P values>0.05). The coincidence rate of T stage diagnosis was 93.0% in the ISR group and 93.5% in the LAR group. The positive rate of circumferential resection margin in the two groups was 0. The mean distance of the distal margin was (2.3±0.1) cm in the ISR group and (1.4±0.3) cm in the LAR group (P<0.001). All patients were followed up for 12-42 (mean 23.4) months. The local recurrence rate was 0 in the ISR group and 12.9% (4/31) in the LAR group (P=0.027); no distant metastasis was observed in any of the groups. There was no significant difference in the results of the anorectal manometry test between the groups (P>0.05). The proportion of patients with good continence of anal function after closure of ileos- tomy was 83.7% in the ISR group and 87.1% in the LAR group (P>0.05). Conclusions: Laparoscopic abdominoperineal intersphincteric resection combined with ileostomy is safe and feasible for the treatment of ultra-low rectal cancer, and it leads to satisfactory anal function and a short-term curative effect.

Gliomas are one of the most common types of brain cancers. Numerous efforts have been devoted to studying the mechanisms of glioma genesis and identifying biomarkers for diagnosis and treatment. To help further investigations, we present a comprehensive database named GliomaDB. GliomaDB includes 21,086 samples from 4303 patients and integrates genomic, transcriptomic, epigenomic, clinical, and gene-drug association data regarding glioblastoma multiforme (GBM) and low-grade glioma (LGG) from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Chinese Glioma Genome Atlas (CGGA), the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), the US Food and Drug Administration (FDA), and PharmGKB. GliomaDB offers a user-friendly interface for two main types of functionalities. The first comprises queries of (i) somatic mutations, (ii) gene expression, (iii) microRNA (miRNA) expression, and (iv) DNA methylation. In addition, queries can be executed at the gene, region, and base level. Second, GliomaDB allows users to perform survival analysis, coexpression network visualization, multi-omics data visualization, and targeted drug recommendations based on personalized variations. GliomaDB bridges the gap between glioma genomics big data and the delivery of integrated information for end users, thus enabling both researchers and clinicians to effectively use publicly available data and empowering the progression of precision medicine in glioma. GliomaDB is freely accessible at http://bigd.big.ac.cn/gliomaDB.

Objective: To investigate the value of single nucleotide polymorphism array (SNP-array) for fetuses with abnormal ultrasound findings. Method: A total of 904 fetuses with abnormal ultrasound findings were enrolled in this study from May 2015 to November 2017, and 434 (48.0%) cases received conventional karyotyping analysis at the same time. According to different abnormal ultrasound category, 904 cases were divided into 5 groups: 280 cases (31.0%) in single system structural anomalies, 31 cases (3.4%) in multiple system structural anomalies, 331 cases (36.6%) in single ultrasound soft marker abnormalities without structural anomalies, 107 cases (11.8%) in multiple soft marker abnormalities and 155 cases (17.2%) in structural abnormalities combined with soft markers abnormalities. Abnormal detection rates by SNP-array among 5 groups of abnormal ultrasound category were calculated. Result: (1) Total SNP-array results: 171 (19.0%) cases out of 904 cases analyzed by SNP-array, presented chromosomal abnormalities. Pathogenic copy number variants were detected in 27 cases (3.0%) and variants of unknown significance were detected in 81 cases (7.8%) . In addition, 7 cases (26.0%) were found with new mutation by parental validation. (2) SNP-array of 5 groups: among the 5 groups of abnormal ultrasound category, chromosomal abnormalities were identified by SNP-array in 19.3% (54/280) with single system structural abnormalities, 25.8% (8/31) with multiple system structural abnormalities, 13.9% (46/331) with single nonstructural anomalies, 19.6% (21/107) with multiple nonstructural anomalies and 27.1% (42/155) with structural abnormalities combined with nonstructural anomalies. The differences were significant (P=0.010) . No chromosome abnormalities was identified in single soft marker abnormalities, such as choroid plexus cysts, echogenic foci in the heart, single umbilical artery and pyelectasis. (3) Chromosomal abnormalities: the abnormal detection rate of aneuploidy chromosomal abnormalities by SNP-array increased with the maternal age, decreased with the gestational weeks (all P<0.05) . However, the pathogenic copy number variants and variants of unknown significance rates did not change with maternal age and gestational weeks (all P>0.05) . (4) SNP-array and karyotyping: 434 cases were analyzed by conventional karyotyping and SNP-array respectively, 10.3% (43/419) of which presented chromosomal abnormalities by conventional karyotyping and 18.7% (81/434) of which presented chromosomal abnormalities by SNP-array. Conclusions SNP-array could be a useful genetic analysis method in prenatal diagnosis for fetuses with abnormal ultrasound findings. For different abnormal ultrasound category, SNP-array has different detection rate. Compared with conventional karyotyping analysis, SNP-array can improve the detection rates for chromosomal abnormalities and find the chromosome abnormalities which can′t be detected by conventional karyotyping analysis. In clinical prenatal genetic counseling, SNP-array should be selected rationally in combination with the various abnormal ultrasound category.

Objective To investigate the value of next-generation sequencing (NGS) technique for genetic analysis of spontaneous abortion. Methods From January to June 2017, 154 patients who visited the First Affiliated Hospital of Zhengzhou University for spontaneous abortion were enrolled. All abortion tissue samples were analyzed by both NGS combined with short tandem repeat (STR) and single nucleotide polymorphism array (SNP-array). Results of the two methods were compared by Chi-square or Fisher's exact test. Results (1) Chromosomal abnormalities were detected in 109 of the 154 cases (70.7%), including 52 (47.7%) of numerical chromosomal abnormalities, 49 (45.0%) of structural chromosomal abnormalities, six (5.5%) of mosaicism, and two (1.8%) of uniparental disomy (UPD). In those 52 cases of numerical chromosome abnormalities, there were 45 of chromosome aneuploidy and seven of polyploidy. The top three numerical chromosomal abnormalities were 45,X (27.0%, 14/52), trisomy 22 (9.6%, 5/52) and trisomy 16 (7.7%, 4/52). Forty-nine structural abnormality cases carried 67 copy number variations (CNV), including 13 pathogenic CNV (pCNV, 19.4%), 24 variants of unknown clinical significance (35.8%) and 30 benign CNV (44.8%). In those 13 pCNVs, two were responsible for microdeletion and microduplication syndromes. (2) SNP-array was successful in 152 cases, but failed in two (1.3%) due to genomic DNA <200 ng. However, NGS technology was successful in all 154 cases and identified chromosomal abnormalities in the two cases that SNP-array had failed. No statistically significant difference was shown in the detection rate of chromosomal abnormalities between SNP-array and NGS technology [70.4% (107/152) vs 67.5% (104/154), χ2=0.293, P=0.588]. (3) No significant difference in the detection of chromosome aneuploidy (six cases in each group, 3.9% vs 3.9%) and mosaicism (45 cases in each group, 29.2% vs 29.6%) was found between NGS technology and SNP-array. Three cases of polyploidy (69, XXX) and two of UPD were identified by SNP-array, but not by NGS. When combined with STR, NGS was able to detect all three cases of polyploidy (69, XXX). (4) Forty-seven structural abnormality cases detected by SNP-array carried 53 CNVs, and 49 detected by NGS carried 67 CNVs. (5) NGS detected ten, three and one more CNVs than SNP-array did when the genome lengths were 100-<500, 500-<1 000 and ≥1 000 kb, respectively. Conclusions NGS can be used to detect chromosomal aneuploidy and mosaicism that can be identified by SNP-array with fewer limitations on total amount of genome. Moreover, CNVs that fail to be identified by SNP-array can also be detected by NGS. When combined with STR, NGS can effectively detect chromosomal polyploidy. Therefore, NGS could be a potential genetic analysis method for spontaneous abortion and of importance for genetic counseling.

Objective: To observe the therapeutic efficacy of alanyl glutamine injection on patients with gastrointestinal function obstacle caused by severe phorate poisoning. Methods: A total of 80 eligible patients with gastrointestinal function obstacle caused by severe phorate poisoning were randomly divided into the control group (n=40) and treatment group (n=40) . The control group was treated with the conventional therapy, which included forbidden diet, atropine, pralidoxime iodide, anti-inflammatory, albumin infusion, ω-3 fish oil fat emulsion, protection of organs function, blood perfusion, and Fat Emulsion, Amino Acids (17) and Glucose Injection. The treatment group was treated with alanyl glutamine injection plus the conventional therapy. To observe the time of recovering to normal of gastrointestinal function between the two groups, compared the AChE activity and changes of prealbumin, albumin and total protein of the two groups respectively. Furthermore, the total atropine dosage, the total pralidoxime iodide dosage and ICU stay time between the two groups were also compared. Results: The gastrointestinal function recovery time of patients in the treatment group was less than the control group, the difference was statistically significant (P<0.05) . From the third day of treatment, the serum cholinesterase activity of the treatment group was higher than the control group, the difference was statistically significant (P<0.05) . On the 5th day and 10th day of the treatment, the prealbumin, albumin and total protein of the treatment group were significantly higher than these indexes of the control group in the same period, the difference were statistically significant (P<0.05) . The total atropine dosage, the total pralidoxime iodide dosage and ICU stay time in the treatment group were lower than the control group, the difference were statistically significant (P<0.05) . Conclusion Alanyl glutamine injection has a great therapeutic effect for gastrointestinal function obstacle patients caused by severe phorate poisoning.