The genetics and clinical outcomes in 151 cases of fetal growth restriction: A Chinese single-center study.

OBJECTIVE: To determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction. Study design A total of 151 fetal samples with intrauterine growth restriction were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored. Results The karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development. Conclusions This study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction.

Comparison of Third-Generation Sequencing and Routine Polymerase Chain Reaction in Genetic Analysis of Thalassemia.

CONTEXT.­: Thalassemia is the most widely distributed monogenic autosomal recessive disorder in the world. Accurate genetic analysis of thalassemia is crucial for thalassemia prevention. OBJECTIVE.­: To compare the clinical utility of a third-generation sequencing-based approach termed comprehensive analysis of thalassemia alleles with routine polymerase chain reaction (PCR) in genetic analysis of thalassemia and explore the molecular spectrum of thalassemia in Hunan Province. DESIGN.­: Subjects in Hunan Province were recruited, and hematologic testing was performed. Five hundred four subjects positive on hemoglobin testing were then used as the cohort, and third-generation sequencing and routine PCR were used for genetic analysis. RESULTS.­: Of the 504 subjects, 462 (91.67%) had the same results, whereas 42 (8.33%) exhibited discordant results between the 2 methods. Sanger sequencing and PCR testing confirmed the results of third-generation sequencing. In total, third-generation sequencing correctly detected 247 subjects with variants, whereas PCR identified 205, which showed an increase in detection of 20.49%. Moreover, α triplications were identified in 1.98% (10 of 504) hemoglobin testing-positive subjects in Hunan Province. Seven hemoglobin variants with potential pathogenicity were detected in 9 hemoglobin testing-positive subjects. CONCLUSIONS.­: Third-generation sequencing is a more comprehensive, reliable, and efficient approach for genetic analysis of thalassemia than PCR, and allowed for a characterization of the thalassemia spectrum in Hunan Province.

Exosomes Derived from Human Adipose-Derived Stem Cells Cannot Distinctively Promote Graft Survival in Cryopreservation Fat Grafting.

BACKGROUND: Cryopreserved fat has limited clinical applications due to its rapid absorption, high degree of fibrosis, and risk of complications after grafting. Many studies have verified that Adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) can improve fresh fat graft survival. This study assessed whether ADSC-Exos could improve the survival of cryopreserved fat grafts. METHODS: Exosomes were isolated from human ADSCs were subcutaneously engrafted with adipose tissues stored under different conditions (fresh; cryopreserved for 1 month) into the backs of BALB/c nude mice (n = 24), and exosomes or PBS were administered weekly. Grafts were harvested at 1, 2, 4, and 8 weeks, and fat retention rate, histologic, and immunohistochemical analyses were conducted. RESULTS: At 1, 2, and 4 weeks after the transfer, cryopreserved fat grafts in groups of exosome-treated showed better fat integrity, fewer oil cysts, and reduced fibrosis. Further investigations of macrophage infiltration and neovascularization revealed that those exosomes increased the number of M2 macrophages at 2 and 4 weeks (p<0.05), but had limited impact on vascularization (p>0.05). It's important to note that no significant differences (p>0.05) were observed between the two groups in both histological and immunohistochemical evaluations at 8 weeks post-transplantation. CONCLUSIONS: This study suggests that ADSC-Exos could improve the survival of cryopreserved fat grafts in the short term (within 4 weeks), but the overall improvement was poor (after 8 weeks). This suggests that the utility of using ADSC-Exos to treat cryopreserved adipose tissue grafts is limited. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Aesthetic Concerns of Chin Augmentation With Hyaluronic Acid Soft Tissue Filler in Chinese: A Prospective, Observational Study.

BACKGROUND: The chin is an important facial structure that directly affects the overall contour of the face. The key to achieving a beautiful, effective, and safe chin injection is to make a good facial assessment and use an appropriate injection technique to achieve the best injection effect. OBJECTIVE: In this article, the authors will discuss cosmetic concepts for the chin area and verify the effectiveness of chin augmentation techniques. MATERIALS AND METHODS: Chin volume injections were performed on 23 Asian female subjects and 15 Asian male subjects. Demographic and imaging data were collected, and the facial aesthetic length was calculated. The authors also measured the length of beautiful chins, as evaluated by 2 plastic surgeons, and the ratios of chins from "The 100 Most Beautiful/Handsome Faces in China" published by TCC Asia in 2020. RESULTS: The mean volume of chin filling was 1.89 ± 0.74 mL in female subjects and 2.68 ± 1.28 mL in male subjects. The ideal length of the chin was equal to that of the nasal dorsum in male subjects, and the ideal chin-to-nasal dorsum ratio was 0.9 in female subjects. CONCLUSION: In this study, the authors investigate sex differences in chin aesthetics among the Chinese population and introduce an aesthetic and anatomical approach to chin injection.

Clinical Anatomy of the Chin Evaluated by 3-Dimensional Tomography and Cadaveric Dissection: Implications for Safety and Optimal Injection Techniques in Chinese.

BACKGROUND: Soft tissue fillers have been widely used for the correction of chin volume loss because of congenital conditions and aging. OBJECTIVE: This study aimed to discuss anatomical concerns for chin filler injections, which may help to reduce the incidence of severe intravascular embolization complications and improve patient satisfaction. METHODS AND MATERIALS: We scanned 40 cadaveric heads with a contrast agent using a 64-row spiral computed tomography scanner. The scan was visualized by a Philips IntelliSpace workstation and analyzed by Materialise's interactive m image control system software to measure and quantify the arterial data. Twenty of 40 cadavers were dissected to define the layers of tissue. RESULTS: In total, 221 arteries passed through the sagittal plane of 40 specimens. The number of superficial arteries (163 of 221) was much greater than the number of deep arteries (58 of 221). The number of arteries gradually decreased with distance from the lower lip vermilion border plane, which formed the lower third of the face. CONCLUSION: This study introduces a safe and effective technique for administering chin filler injections that minimizes risks and improves patient satisfaction.

Serratus Plane Block in Breast Cancer Surgery: A Systematic Review and Meta-Analysis.

The serratus plane block is a regional anesthesia technique awaiting efficacy and safety evaluation in breast cancer surgery, but evidence is unclear. This meta-analysis evaluates the analgesic effectiveness of serratus plane block vis-à-vis general anesthesia and paravertebral block for breast cancer surgery. We searched for randomized controlled trials in PubMed, the Cochrane Library, and Web of Science with no language limitation, comparing the serratus plane block with multimodal analgesia or the thoracic paravertebral block in breast cancer surgery. The Hartung-Knapp-Sidik-Jonkman method in combination with a random-effects model was used to pool data. We included 12 randomized controlled trials (799 patients). Compared with multimodal analgesia, pooled outcomes favored the use of serratus plane block for effectively alleviating acute postoperative pain severity at multiple time points. The serratus plane block also resulted in decreased postoperative analgesic consumption of 28.81mg (95% confidence interval [CI]: -51.20, -6.43), decreased intraoperative fentanyl consumption of -56.46 mg (95% CI: -79.61, -33.30), increased duration of postoperative anesthesia of 243.85 min (95% CI: 104.38, 383.31), and reduced postoperative nausea and vomiting with a log relative risk of -1.07 (95% CI: -1.90, -0.24). Compared with the thoracic paravertebral block, the serratus plane block was not statically worse for all of the outcomes assessed. No adverse effects were reported. The serratus plane block effectively alleviates acute postoperative pain, reduces the rate of postoperative nausea and vomiting, and improves perioperative anesthesia outcomes in breast cancer surgery, and it may represent an alternative to thoracic paravertebral block.

Prenatal genetic diagnosis of tetrasomy 18p from maternal trisomy 18p: a case report.

BACKGROUND: Tetrasomy 18p syndrome is a rare chromosomal disorder that is caused by the presence of isochromosome 18p. Most tetrasomy 18p cases are de novo cases and maternal origin of trisomy 18p is a rare condition. At present, only four cases of maternal origin have been reported in worldwide.This is the fifth case of tetrasomy 18p originating from maternal trisomy 18p. The mother of the fetus studied had no apparent disease phenotype. CASE PRESENTATION: The current case report is to describe a fetus with confirmed 18p tetrasomy as detected by karyotyping and Single Nucleotide Polymorphism array (SNP array) analysis. However, the fetus showed normal phenotypic features that were observed using ultrasound scans. The mother and maternal grandfather were phenotypically normal and healthy; however, they were diagnosed with trisomy 18p, which was confirmed by conventional karyotyping and SNP array. CONCLUSIONS: We report a case of 18p tetrasomy in a fetus whose mother and grandfather had 18p trisomy. The mother and grandfather were phenotypically normal. Our case report findings provide an important reference for the genetic counseling of trisomy 18p in the future.

Prenatal diagnosis of complete paternal uniparental isodisomy for chromosome 3: a case report.

BACKGROUND: Uniparental disomy (UPD) is defined as an inheritance of two chromosomes from only one of the parents with no representative copy from the other. Paternal-origin UPD of chromosome 3 is a very rare condition, with only five cases of paternal UPD(3) reported. CASE PRESENTATION: Here, we report a prenatal case that is only the second confirmed paternal UPD(3) reported with no apparent disease phenotype. The fetus had a normal karyotype and normal ultrasound features throughout gestation. Copy neutral regions of homozygosity on chromosome 3 were identified by single nucleotide polymorphism (SNP) array. Subsequent SNP array data of parent-child trios showed that the fetus carried complete paternal uniparental isodisomy (isoUPD) of chromosome 3. The parents decided to continue with the pregnancy after genetic counseling, and the neonate had normal physical findings at birth and showed normal development after 1.5 years. CONCLUSIONS: These findings provided further evidence to confirm that there were no important imprinted genes on paternal chromosome 3 that caused serious diseases and a reference for the prenatal diagnosis and genetic counseling of UPD(3) in the future.

Six novel Mutation analysis of the androgen receptor gene in 17 Chinese patients with androgen insensitivity syndrome.

BACKGROUND: Androgen insensitivity syndrome (AIS) is the most common type of 46, XY disorders of sex development (DSD), with a wide range of clinical heterogeneity, from male infertility, hypospadias to completely normal female external genitalia. Mutation of the androgen receptor (AR) gene on the X chromosome (Xq11.2q12) is the main cause of AIS. METHODS: By phenotype evaluation, hormone test, ultrasound scan and G-banding karyotype, 17 unrelated Chinese patients were clinical diagnosed with AIS. Sanger sequencing of the AR was performed in these 17 patients. Functional studies were carried out for the novel mutations. RESULTS: We identified 16 mutations in all patients, including six novel mutations (Q59*, F171Sfs*4, E204*, G209E, I870T, *921R). It is the first time that a stop codon mutation (*921R) in AR has been identified. Expression and nuclear localization analysis showed the *921R mutation caused an elongated abnormal polypeptide chain of the AR protein, and the abnormal protein could not be transported to the nucleus to stimulate the expression of downstream genes after androgenic treatment. Expression analysis showed the protein level of G209E mutation was obviously decreased. CONCLUSION: Our study expands the spectrum of AR mutations and could provide evidence for the genetic and reproductive counseling of families with AIS. All of these findings broadened the mutation spectrum of AR, which were significantly valuable for patient gender assignment, genetic counseling and the clinical and psychological management.

28 novel mutations identified from 33 Chinese patients with cilia-related kidney disorders.

BACKGROUND: Cilia play an important role in cellular signaling pathways. Defective ciliary function causes a variety of disorders involve retina, skeleton, liver, kidney or others. Cilia-related kidney disorders are characterized by cystic renal disease, nephronophthisis and renal failure in general. METHODS: In this study, we collected 33 families clinically suspected of cilia-related kidney disorders. Capture-based next-generation sequencing (NGS) of 88 related genes, Sanger sequencing, pedigree analysis and functional study were performed to analyze their genetic cause. RESULTS: 40 mutations in PKD1, PKD2, PKHD1, DYNC2H1 and TMEM67 genes were identified from 27 of 33 affected families. 70% (28/40) of the mutations were first found in patients. We reported a very early-onset autosomal dominant polycystic kidney disease (ADPKD) family caused by a novel heterozygous PKD1 mutation; another fetus with DYNC2H1 compound heterozygous missense mutations showed mainly kidney dysplasia instead of skeletal abnormalities; and a novel PKD1 mutation, c.12445-3C > G, was confirmed to cause two wrong splicing modes. As for previously reported mutations, such as PKD1, c.6395 T > G (p.F2132C) and c.6868G > T (p.D2290Y), we had new and different findings. CONCLUSION: The findings provided new references for genotype-phenotype analyses and broadened the mutation spectrum of detected genes, which were significantly valuable for prenatal diagnosis and genetic counseling.