Objective:To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification.Methods:A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78).Results:The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c. 728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband′s father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+ PM2_Supporting+ PP2+ PP3+ PP4). Conclusion:The heterozygous c. 728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c. 728C>T variant of the TUBB8 gene, oocyte donation may be considered.

Objective To obtain the protective performance parameters of barium sulfate mortar against positron nuclide γ-rays, provide reference data for precise shielding calculations, and guide the design, evaluation, and construction of radiation shielding. Methods The FLUKA program was used to build a model for simulating the dose equivalent rate variation around points of interest under the irradiation of the most commonly used positron nuclide ¹⁸F with changes in the thicknesses of lead and barium sulfate mortar. The transmission curves of lead and barium sulfate mortar were fitted, and the half-value layer (HVL) and lead equivalence of barium sulfate mortar were calculated based on the fitted curves. Results The ambient dose equivalent rate coefficient of positron nuclide ¹⁸F was 1.339 4×10⁻¹ μSv·m²/MBq·h and the HVL for lead was 4.037 mm, with deviations of 0.043% and 1.53% compared to the values provided in the AAPM Report No. 108, respectively. The HVLs for γ-rays produced by ¹⁸F, using barium sulfate mortar with apparent densities of 4.20, 4.00, and 3.90 g/cm³ mixed with 35.2-grade cement in a 4∶1 mass ratio, were 2.914, 2.969, and 3.079 cm, respectively. The lead equivalences were 0.1385, 0.1360, and 0.1311 mmPb/mm, respectively. Conclusion The three types of barium sulfate mortar can provide good protection against γ-rays in positron imaging locations. As the apparent density of barium sulfate increases, its protective effect improves slightly but remains significantly better than common construction materials like concrete and solid bricks.

OBJECTIVE: To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification. METHODS: A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband's father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+PM2_Supporting+PP2+PP3+PP4). CONCLUSION The heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c.728C>T variant of the TUBB8 gene, oocyte donation may be considered.
Humans ; Female ; Adult ; Mutation, Missense ; Oocytes/metabolism* ; Heterozygote ; Tubulin/genetics* ; Infertility, Female/genetics* ; High-Throughput Nucleotide Sequencing ; Pedigree

OBJECTIVE: To investigate the clinical phenotype and genetic etiology of a patient with primary infertility accompanied by Oocyte maturation defect (OOMD). METHODS: A 24-year-old female patient who visited the Reproductive Medicine Center of Gansu Provincial Maternity and Child Care Hospital in April 2024 was selected as the study subject. Whole-exome sequencing (WES) was performed on the proband and her husband. Candidate gene variants were validated in the family using Sanger sequencing, and compound heterozygous variants were confirmed through vector construction. Candidate variants were classified for pathogenicity according to the "Standards and Guidelines for the Interpretation of Sequence Variants" established by the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Hospital [Ethics No.: (2023) GSFYLS(78)]. RESULTS: The proband, a 24-year-old female, had been unable to conceive for four years without contraception after marriage. She had undergone two ovarian stimulation cycles using the antagonist protocol and the PPOS protocol, respectively. A total of 74 oocytes were retrieved, with all showing OOMD and some oocytes exhibiting abnormal morphology and poor quality. WES results revealed two heterozygous missense variants in exons 14 and 16 of the PATL2 gene: c.1127G>A (p.R376Q) and c.1388C>G (p.A463G). Family validation results indicated that the missense variant in exon 14 was inherited from the proband's father, while the variant in exon 16 was de novo. CONCLUSION The compound heterozygous variants of the PATL2 gene probably underlay the OOMD and infertility in this proband. Further analysis based on the variant sites and protein structures is needed to determine whether PATL2 gene variants can fully affect oocyte development, thereby providing a personalized treatment plan for the proband.
Female ; Humans ; Young Adult ; Exome Sequencing ; Infertility, Female/genetics* ; Oocytes/metabolism* ; Pedigree ; Phenotype

Chronic limb-threatening ischemia(CLTI)is a serious peripheral arterial disease(PAD)characterized by reduced blood flow in the limbs,resulting in tissue damage and dysfunction.Mesenchymal stem cells(MSCs)have become a research hotspot in the field of CLTI treatment in recent years due to their unique regenerative ability and immunomodulatory properties.In the environment of hypoxia and tissue injury,MSCs can promote angiogenesis,reduce inflammation and promote tissue repair by secreting cytokines,cell differentiation and inter-cellular signal transduction,so as to improve the symptoms and prognosis of patients with CLTI,showing a broad clinical application prospect.

Vitrification is a critical embryo cryopreservation technique extensively employed in assisted reproductive technology clinical practice. Recent evidence from animal models and clinical studies indicates that vitrification may compromise embryonic developmental competence by inducing epigenetic alterations, including dysregulated DNA methylation patterns, aberrant histone modifications, and subsequent disruptions in gene expression regulation. This review systematically summarizes recent advances from both animal and human studies, highlighting molecular mechanisms underlying vitrification-induced changes in embryonic developmental potential, with particular emphasis on epigenetic and developmental consequences of repeated vitrification. The aim of this review is to provide reproductive genetic insights and theoretical references to facilitate standardized clinical application of vitrification procedures and comprehensive assessment of embryo safety.

Vitrification is a critical embryo cryopreservation technique extensively employed in assisted reproductive technology clinical practice. Recent evidence from animal models and clinical studies indicates that vitrification may compromise embryonic developmental competence by inducing epigenetic alterations, including dysregulated DNA methylation patterns, aberrant histone modifications, and subsequent disruptions in gene expression regulation. This review systematically summarizes recent advances from both animal and human studies, highlighting molecular mechanisms underlying vitrification-induced changes in embryonic developmental potential, with particular emphasis on epigenetic and developmental consequences of repeated vitrification. The aim of this review is to provide reproductive genetic insights and theoretical references to facilitate standardized clinical application of vitrification procedures and comprehensive assessment of embryo safety.

Objective:To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification.Methods:A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78).Results:The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c. 728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband′s father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+ PM2_Supporting+ PP2+ PP3+ PP4). Conclusion:The heterozygous c. 728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c. 728C>T variant of the TUBB8 gene, oocyte donation may be considered.

Objective:To explore the genetic basis for a patient with repeated fertilization failure during assisted reproductive therapy, and to identify the source and mode of mutation.Methods:A couple treated at the Center for Reproductive Medicine, Gansu Provincial Maternal and Child Health Care Hospital in January 2024 for infertility with incomplete left tube obstruction was selected as the study subject. Relevant clinical data was collected. The couple was subjected to whole exome sequencing (WES), and the candidate variant was verified by Sanger sequencing of their family members and bioinformatic analysis. The study has been approved by the the Center for Reproductive Medicine, Gansu Provincial Maternal and Child Health Care Hospital(Ethic No.2023GSFYLS78).Results:WES has identified a homozygous c. 495del frameshifting mutation of the WEE2 gene in the female partner, whilst no relevant variant was suspected in the male partner. The elder brother of the female partner was homozygous for the above variant, while her parents, aunts, uncle, grandmother, and grandmother were heterozygous for it. Based on the guidelines from the American College of Medical Genetics and Genomics, above variant was rated to be pathogenic. Conclusion:The homozygous c. 495del frameshifting mutation of the WEE2 gene probably underlay the oocyte fertilization disorder in this couple.

Diabetic nephropathy(DN)is one of the major microvascular complications caused by diabetes.Functional MRI(fMRI)techniques are sensitive and non-invasive,which can assess renal cortex and medullary damage in early DN,and reveal renal cortex and medullary perfusion abnormalities and molecular diffusion changes in early DN.The research progresses of diffusion tensor imaging(DTI),intravoxel incoherent motion(IVIM)and modified Dixon water-fat separation techniques for evaluating DN were reviewed in this article.