HA of H1N1 enhanced the expression of ICAM-1 and IL-6 in HUVECs and pathological injury in the lungs in mice.

OBJECTIVE: Both COVID-19 and influenza are viral respiratory tract infections and the epidemics of viral respiratory tract infections remain highly prevalent with lethal consequences in susceptible individuals. Expression of ICAM-1 on vascular endothelium recruits leukocytes which initiates inflammation. IL-6 induces ICAM-1. Both ICAM-1 and IL-6 can be enhanced in influenza virus infection and COVID-19 patients. Besides initiation of virus entry host cells, whether HA alone, instead of whole virus, of influenza has the effects on expression of ICAM-1 and IL-6 in vascular endothelium with injury in the lungs, remains to be demonstrated. METHODS: RT-qPCR and Western blot as well as histopathologic examination were used to examine mRNA and protein of ICAM-1 and IL-6 as well as pathological injury in the lung tissues, respectively. RESULTS: After incubation of the Human Umbilical Vein Endothelial Cells (HUVECs) with HA of H1N1 for 24 h, the mRNA and protein of ICAM-1 and IL-6 in HUVECs were increased in group of 5 µg/ml concentration with statistical significance (p < 0.05). Pathological injury in lung tissues of the mice was shown 12 h after tail intravenous injection with 100 µl of HA (50 µg/ml and 100 µg/ml in normal saline), including widened alveolar spaces with angiotelectasis in alveolar wall, alveolar luminal and interstitial inflammatory infiltrates, alveolar luminal erythrocyte effusion. CONCLUSIONS: HA alone, instead of whole H1N1 virus, induced more expression of ICAM-1 and IL-6, two molecules involving in pathological and inflammatory responses, in HUVECs and pathological injury in lung tissues of the mice. This knowledge provides a new HA-targeted potential direction for prevention and treatment of disease related to H1N1 infection.

Endoscopic diagnosis of early-stage primary esophageal small cell carcinoma: Report of two cases.

BACKGROUND: Primary esophageal small cell carcinoma (PESCC) is a highly aggressive malignancy, and its detailed clinical behaviors have remained virtually unknown. Because of the rapid tumor progression, the diagnosis of esophageal small cell carcinoma at early stage is extremely difficult in clinical practice. Currently, only a handful of PESCC cases have been reported. CASE SUMMARY: Case 1: A 62-year-old man was diagnosed with an esophageal submucosal tumor by endoscopy. Endoscopic ultrasonography showed a 0.8 cm low echo nodule in the muscularis mucosa. As the patient refused to undergo endoscopic resection, neoplasia was detected by endoscopy 1 year later. Case 2: A 68-year-old woman was diagnosed as having an esophageal submucosal tumor by endoscopy at a local hospital. About 2 wk later, we performed endoscopic ultrasonography and found a 1 cm low echo nodule in the muscularis mucosa; the submucosal was thinner than normal but still continuous; mucosal hyperemia and erosion were found on the surface of the tumor. Endoscopic submucosal dissection (ESD) was performed and the histopathological finding showed a small cell carcinoma invading the submucosal layer. CONCLUSION: Early esophageal small cell carcinoma shows submucosal infiltrating growth with a hypoechoic mass in the muscularis mucosa as diagnosed by endoscopic ultrasonography. It is easily misdiagnosed as submucosal masses. Endoscopic manifestations should be identified and pathological biopsies should be employed. ESD may be performed to provide an opportunity for early treatment of PESCC.

A Rare Case of Hb H Disease and Systemic Lupus Erythematosus.

Anemia is common in patients with systemic lupus erythematosus (SLE). The association between thalassemia and SLE is rare. In this study, we report the first patient who was found to have a severe hemolytic anemia caused by combination of SLE and Hb H disease. The patient had a more severe presentation in the hematological system. Our case indicates that for a patient who was diagnosed with SLE and developed deterioration in her hematological cell lines, investigation of other possible coexisting causes would be warranted.

Lpl-C310R mutation is associated with impaired glucose tolerance and endoplasmic reticulum stress in skeletal muscle.

Primary Hypertriglyceridemia refers to a loss-of-function genetic defect which prevents the triglyceride (TG) in chylomicrons (CM) from lipolysis, leading to the accumulation of TG. The mutation of lipoprotein lipase (LPL) gene has been recognized as the main cause of primary hypertriglyceridemia. Recently, a new LPL gene mutation p.C310R(c. T928C) was identified in a family with hypertriglyceridemia. The proband was manifested by severe hypertriglyceridemia and diabetes. Skeletal muscle is the major LPL-synthesizing tissue and insulin response target tissue. However, little is known about the effects of LPL gene mutation on skeletal muscle. This study is intended to observe the effects of LPL-C310R mutation on glycolipid metabolism and skeletal muscle. We found that a significantly decreased LPL plasma concentration, activity and the expression levels in skeletal muscle were observed in LplC310R/+ mice comparing to wild type mice. Those mutant mice also exhibited increased fasting plasma TG, free fat acids (FFA) and insulin, as well as FFA in muscle, and decreased glucose tolerance. Enhanced expression of BIP and elevated phosphorylation of IRE1α were observed in skeletal muscle, suggesting increased endoplasmic reticulum stress (ERS). Consistent with this, increased phosphorylation of JNK was also observed. Meanwhile, remarkably enhanced phosphorylation of IRS-1 (Ser307) and decreased phosphorylation of AKT were observed in skeletal muscle of mutant mice, suggesting impaired insulin signaling. Significant lipid deposition and morphological changes in endoplasmic reticulum and mitochondria were observed in the skeletal muscle of mutant mice but not in wild type control. Results demonstrate Lpl C310R mutation caused impaired glucose tolerance, ER stress and impaired insulin signaling in skeletal muscle.

Male age is more critical to sperm DNA integrity than routine semen parameters in Chinese infertile males.

This retrospective study evaluated the correlation between the sperm DNA integrity results and infertile male age or sperm motility in 654 infertile men undergoing infertility evaluations from 2013 to 2016. The correlation between the results of sperm DNA integrity and male age was positive, while a negative correlation was detected between sperm DNA integrity and sperm motility in all subjects. According to age (≤30, 30-35 and ≥35), men with normozoospermia or abnormal semen parameters were, respectively, divided into groups 1, 2 and 3, or groups A, B and C. The sperm DNA fragmentation index (DFI) and DFI abnormality rates in groups 3 and C were highest among their respective cohorts. But they were not significantly different between groups within the same age range. Statistically significant differences were found in male age, progressive motility, as well as total motility between patients with normal DFIs and those with abnormal DFIs in group C, but not in group 3. Older (≥35 years) infertile men have increased sperm DNA fragmentation, independent of conventional semen parameters. Male age is more critical to sperm DNA integrity than routine semen parameters.

Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with ß-Thalassemia Major: A Meta-Analysis.

BACKGROUND: Endocrinopathies are common in patients with ß-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in ß-thalassemia major based on a meta-analysis. METHODS: PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in ß-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with ß-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted. RESULTS: A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in ß-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in ß-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias. CONCLUSION: High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in ß-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

[Alleles dropout patterns of Y-short tandem repeats in infertile males with Y chromosome microdeletions].

Y chromosomal short tandem repeat (Y-STR) typing is the most commonly used genetic technique in forensic studies. However, there may be a limit to the application of Y-STR in forensic science as Y-STR loci are subject to loss or variation caused by the higher chromosomal structures' spontaneous mutation rate. Located in the long arm of the Y chromosome, azoospermia factor (AZF) have been shown to participate in spermatogenesis and its deletion could cause infertility. However, little is known about the Y-STR dropout pattern in individuals with Y chromosome microdeletions. In this study, 85 infertile males with Y chromosome interstitial deletion were identified and special Y-STR allele dropout patterns were analyzed by employing a Y-STR Commercial Kit and a Y chromosome Deletion Kit. Results demonstrate that AZF a region deletion are related to DYS439-DYS389I-DYS389II alleles dropout, while AZF b region or c region deletions correlate to DYS448 allele dropout. Null DYS385-DYS392-DYS448 alleles were observed in AZF b+c+d region deletion individuals. While null DYS390-Y-GATA-H4-DYS385-DYS392-DYS448 alleles were observed in AZF a+b+c+d large region deletion individuals. Our data suggest that Y chromosome microdeletions may indicate specific Y-STR locus dropout patterns.

Phenotypic and Genetic Characterization of Botrytis cinerea Population from Kiwifruit in Sichuan Province, China.

Botrytis cinerea (anamorph of Botryotinia fuckeliana) causes gray mold on numerous plants, including kiwifruit. The primary aim of this study was to investigate the phenotypic and genetic characteristics of the Botrytis cinerea population from kiwifruit in Sichuan Province, China. In all, 176 isolates were collected from kiwifruit orchards from eight geographic regions in Sichuan. All isolates were identified as B. cinerea sensu stricto based on the combined datasets, including morphological criteria, determination of the Bc-hch allele, and phylogenetic analysis of the genes RPB2, G3PDH, and HSP60. Three colony types (i.e., sclerotial, mycelial, and conidial) were observed on potato dextrose agar after 2 weeks, with sclerotial isolates, the predominant category, accounting for 40.91%. No obvious differences in microscopic characteristics were observed among the three types. Three genotypes of transposable elements were identified in the B. cinerea population: boty, flipper, and transposa types. The most prevalent genotype from different geographic populations of B. cinerea was transposa; in contrast, the flipper genotype accounted for only 3.98% of the total population, whereas the vacuma genotype was absent. According to MAT locus amplification, 87 and 89 isolates are MAT1-1 and MAT1-2 type, respectively, and the two mating types were found to be balanced overall in the population. Forty-eight representative isolates were all able to cause gray mold to some extent, and disease severities were significantly different between the cultivars Hongyang and Hort16A (P < 0.01). Disease severity was significantly greater on young leaves than on mature leaves (P < 0.01). No significant relationship was found between pathogenicity and geographical region, colony type, or transposon distribution. The results obtained in the present study suggest a relatively uniform species diversity of Botrytis but rich phenotypic and genetic differentiation within the B. cinerea population on kiwifruit in China. Utilizing resistant cultivars and rain-shelter cultivation instead of fungicides may be an effective approach to delaying pathogen variability.

Cytogenic and molecular studies of male infertility in cases of Y chromosome balanced reciprocal translocation.

Y-autosomal translocation has been previously reported in association with male infertility; however, the mechanisms of Y-autosomal translocation and non­obstructive azoospermia or severe oligospermia remain unclear. G­banding and fluorescence in situ hybridization (FISH) were performed to analyze the translocation of chromosomes, and a single nucleotide polymorphism (SNP) genotyping assay was used to test mutations. The present study describes three new cases with a de novo balanced translocation t(Y;13), t(Y;9) and t(Y;6). To further explore the genotype­phenotype correlation, G­banding and FISH were performed and indicated the presence of a derivative chromosome. The SNP genotyping assay using a microarray revealed no abnormality, especially in the Y chromosome. Molecular deletion analysis demonstrated that no microdeletion was detected in the azoospermia factor region of the Y chromosome in the examined, infertile men. Based on these observations, the authors proposed the hypothesis that a position effect involving unknown spermatogenesis regulatory gene(s) serves a key role in male infertility.

Protective effect of antioxidants on the pre-maturation aging of mouse oocytes.

Pre-maturation aging of immature oocytes may adversely affect the fate of an oocyte. Oxidative stress is one of the most detrimental factors affecting oocyte developmental competence and maturation during aging. In this study, experiments were designed to examine whether supplementation of antioxidants in a culture medium could protect immature mouse oocytes from damages caused by oxidative stress. Mouse oocytes at germinal vesicle stage were prevented from meiosis resumption and cultured in a medium with or without antioxidants for 12-36 h to allow oocytes to undergo aging. After aging, oocytes were cultured for maturation. Nuclear maturation, mitochondria activity, spindle morphology and DNA integrity were examined after maturation. It was found that antioxidants had protective effects on the oocytes in terms of nuclear maturation, functional mitochondria, spindle morphology and DNA integrity. As aging time was prolonged from 12 to 36 h, the protective effect of antioxidants became more obvious. However, as compared with oocytes without aging, it was found that aging significantly inhibited nuclear maturation, impaired mitochondria function, and damaged the spindle and DNA. These results indicate that pre-maturation aging is detrimental to oocytes' competence to undergo maturation and other cellular activities, and antioxidants can protect oocytes from damages caused by aging.

[Effects of Different Culture Systems on the Hematopoietic Differentiation Ability of iPS Cells].

OBJECTIVE: To investigate the in vitro effects of different culture systems on hematopoietic differentiation ability of induced pluripotent stem (iPS) cells. METHOD: Two culture systems including E8 and mTESR(freeder-free medium), and the classical ES culture medium were chosen for culture of iPS cells. The iPS cells maintaining in above mentioning culcure systems were co-cultured with OP9 cells(murine bone marrow stromal cells) in vitro to be induced to differentiate into hematopoietic stem/progenitor cells. Flow cytometry and real-time quantitative PCR were used to detect the expression of specific hematopoietic markers and the effects of different culture systems on the differentiation of iPS in vitro. RESULT: iPS cultured in the 3 selected medium could be differentiated into hematopoietic stem cells. Efficiency of hematopoietic differentiation was up to 28.4% in classical ES culture system, which was significantly higher than that in E8 and mTESR system. CONCLUSION: Under the co-culture with OP9, iPS can differentiate into hematopoietic stem/progenitor cells, which shows higher efficiency when iPS maintained in the ES medium.

Rad9a is required for spermatogonia differentiation in mice.

Spermatogenesis in testes requires precise spermatogonia differentiation. Spermatocytes lacking the Rad9a gene are arrested in pachytene prophase, implying a possible role for RAD9A in spermatogonia differentiation. However, numerous RAD9A-positive pachytene spermatocytes are still observed in mouse testes following Rad9a excision using the Stra8-Cre system, and it is unclear whether Rad9a deletion in spermatogonia interrupts differentiation. Here, we generated a mouse model in which Rad9a was specifically deleted in spermatogonial stem cells (SSCs) using Cre recombinase expression driven by the germ cell-specific Vasa promoter. Adult Rad9a-null male mice were infertile as a result of completely blocked spermatogonia differentiation. No early spermatocytes were detected in mutant testicular cords of 9-day-old mice. Mutant spermatogonia were prone to apoptosis, although proliferation rates were unaffected. Rad9a deletion also resulted in malformation of seminiferous tubules, in which cells assembled irregularly into clusters, and malformation led to testicular cord disruption. Our findings suggest that Rad9a is indispensable for spermatogonia differentiation and testicular development in mice.

Combined chromium and magnesium decreases insulin resistance more effectively than either alone.

BACKGROUND AND OBJECTIVES: Peroral supplementation with trivalent-chromium (Cr) or magnesium (Mg) has been shown to improve insulin resistance (IR). The objective of this study was to determine whether combined peroral supplementation with Cr and Mg improves IR more effectively than Cr or Mg alone. METHODS AND STUDY DESIGN: Subjects (n=120, age range 45-59 years old) and diagnosed with IR were randomly divided into four groups and monitored for a period of 3 months: group 1 (the placebo control group), group 2 (160 µg/d Cr), group 3 (200 mg/d Mg), and group 4 (160 µg/d Cr plus 200 mg/d Mg). Fasting blood glucose (FBG), fasting insulin (FIns), erythrocyte Cr and Mg content, and glucose-transporter-4 (GLUT4) and glycogen-synthase-kinase-3ß (GSK3ß) mRNA levels in activated T-lymphocytes were measured, and insulin resistant index (IRI) was calculated. RESULTS: Significant decreases between the baseline and study conclusion values of FBG (0.37 mmol/L, p<0.01), FIns (2.91 µIU/mL, p<0.01) and IRI (0.60, p<0.01) were observed in group 4, but not groups 1-3. Similarly, compared with baseline, significant changes in GLUT4 (2.9-fold increase, p<0.05) and GSK3ß (2.2-fold decrease, p<0.05) mRNA levels in activated T-lymphocyte were observed at the study's conclusion in group 4, but not in groups 1-3. CONCLUSIONS: Our results indicate that combining peroral supplementation with Cr and Mg improves IR more effectively than Cr or Mg alone, and this may be attributable to increased induction and repression, respectively, of GLUT4 and GSK3ß expression.

Prenatal diagnosis of hemivertebrae--A likely association with 7q deletion.

OBJECTIVE: This study aims to investigate the possible cause of a prenatal case of hemivertebrae with a 7q terminal deletion. CASE REPORT: This case describes a fetus with hemivertebrae in thoracic vertebrae as the sole antenatal sonographic finding. Genetic testing was performed in order to find more information after the abnormal ultrasound finding. The array-based comparative genomic hybridization results showed that the fetus had approximately 6.4 Mb deletion of 7q36. We discussed the two genes (SHH and HLXB9) that may be associated with hemivertebrae in the deletion region and reviewed several literatures about 7q36 deletion. CONCLUSION: Our results suggest that the phenotype of hemivertebra in our case may be related to the deletion of 7q36.

Naïve Induced Pluripotent Stem Cells Generated From ß-Thalassemia Fibroblasts Allow Efficient Gene Correction With CRISPR/Cas9.

UNLABELLED: Conventional primed human embryonic stem cells and induced pluripotent stem cells (iPSCs) exhibit molecular and biological characteristics distinct from pluripotent stem cells in the naïve state. Although naïve pluripotent stem cells show much higher levels of self-renewal ability and multidifferentiation capacity, it is unknown whether naïve iPSCs can be generated directly from patient somatic cells and will be superior to primed iPSCs. In the present study, we used an established 5i/L/FA system to directly reprogram fibroblasts of a patient with ß-thalassemia into transgene-free naïve iPSCs with molecular signatures of ground-state pluripotency. Furthermore, these naïve iPSCs can efficiently produce cross-species chimeras. Importantly, using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease genome editing system, these naïve iPSCs exhibit significantly improved gene-correction efficiencies compared with the corresponding primed iPSCs. Furthermore, human naïve iPSCs could be directly generated from noninvasively collected urinary cells, which are easily acquired and thus represent an excellent cell resource for further clinical trials. Therefore, our findings demonstrate the feasibility and superiority of using patient-specific iPSCs in the naïve state for disease modeling, gene editing, and future clinical therapy. SIGNIFICANCE: In the present study, transgene-free naïve induced pluripotent stem cells (iPSCs) directly converted from the fibroblasts of a patient with ß-thalassemia in a defined culture system were generated. These naïve iPSCs, which show ground-state pluripotency, exhibited significantly improved single-cell cloning ability, recovery capacity, and gene-targeting efficiency compared with conventional primed iPSCs. These results provide an improved strategy for personalized treatment of genetic diseases such as ß-thalassemia.

[Geo-spectrum characteristics of land use change in Jiangsu Province, China.] / 江苏省土地利用变化的图谱特征.

This paper studied the spatial-temporal characteristics and rules of land use change in Jiangsu Province using theories and methods of geo-spectrum. Based on the land use data translated from remote sensing images of 1990, 2000 and 2010, we synthesized the geo-spectrum of the mode of arable land use change and that of land use change in two corresponding phases, 1990-2000 and 2000-2010, in Jiangsu using ArcGIS 10.0. The results showed that in the phase of 1990-2000, the major characteristics of land use change were swaps between the geo-spectrum unit of arable land and urban-rural construction land, arable land and water body, and arable land and grassland. Specifically, the patterns of "arable land → urban-rural construction land" and "arable land→ water body" were highly significant. We also found the reduction of arable land area and the concentration of its spatial distribution. In the phase of 2000-2010, the "arable land → urban-rural construction land" pattern was still the most salient characteristic. In addition, the patterns of "grassland → water body" and "urban-rural construction land → water body" became more spatially concentrated and tended to expand. Compared with the previous phase, the area of the land use in the phase of 2000-2010 had been changed expanded and became more scattered. Overall, the geo-spectrum of arable land use change in Jiangsu was mainly shaped by the anaphase change type and partially by the prophase change type, with a tiny influence of the repeated and continuous change.

Positive Association Between Type 2 Diabetes Risk Alleles Near CDKAL1 and Reduced Birthweight in Chinese Han Individuals.

BACKGROUND: Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKAL1, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population. METHODS: Twelve single nucleotide polymorphisms (rs7756992/rs10946398 in CDKAL1, rs1111875 in HHEX, rs391300 in SRR, rs17584499 in PTPRD, rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5) were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed. RESULTS: Birthweight was inversely associated with CDKAL1-rs10946398 (ß = -41 g [95% confidence interval [CI]: -80, -3], P = 0.034), common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight (ß = -36 g [95% CI: -72, -0.2], P = 0.048). The risk allele in SRR showed a trend toward a reduction of birthweight (P = 0.085). CONCLUSIONS: This study identified the association between type 2 diabetes risk variants in CDKAL1 and birthweight in Chinese Han individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.

Genetic Evaluation of Copy Number Variations, Loss of Heterozygosity, and Single-Nucleotide Variant Levels in Human Embryonic Stem Cells With or Without Skewed X Chromosome Inactivation.

Human embryonic stem cells (hESCs) exhibiting skewed X chromosome inactivation (XCI) have been reported. The copy number variations (CNVs), loss of heterozygosity (LOH), or single-nucleotide variant (SNV) events in those epigenetically distinct cells remain unknown, and whether such genetic abnormalities will influence the XCI status of hESCs is unclear. In this study, three hESCs with skewed XCI, three with random XCI, and two male hESC lines at different passages were analyzed for CNVs and LOH levels using a high-resolution genotyping microarray. Whole-exome sequencing was used to investigate the potentially damaging SNVs. On average, 17.6 CNVs and 5.3 cases of LOH were identified in the skewed hESCs, which were similar to the rates observed in random hESCs. Five recurrent CNV regions were uniquely identified in the skewed hESCs, but all of them were considered polymorphisms. With the exception of a nongenic CNV, no additional CNVs were detected on the X chromosome in the skewed hESCs. Although the XCI status in two hESC lines was observed to be changed from random to skewed, no significant CNV difference was identified before and after the XCI change. SNV analysis indicated that normal alleles are maintained for most genes within copy-neutral LOH regions. Three types of expression patterns were observed in heterozygous alleles, and the damaging SNVs in skewed hESCs favored the expression of the wild-type alleles. In conclusion, in the present study, we did not find genetic differences in the CNV and LOH levels between hESCs with and without skewed XCI. Wild-type allele expression in the presence of damaging SNVs on the X chromosome in skewed hESCs might alleviate adverse effects in those hESCs.