Large inter-individual and intra-individual differences in the expression and activity of drug-metabolizing enzymes(DMEs)contribute to unpredictable drug response and toxicity,which is a challenge facing precision medicine.Nuclear receptor-mediated transcriptional regulation and epigenetic mechanisms including histone modifications,non-coding RNAs,and DNA methylation can help to explain the individual variability in DME expressions.However,several questions remain unanswered.Recently,epitranscriptomics,an emerging field,provides new insights into the regulation of gene expression.As the most abundant RNA modification in eukaryotes,N6-methyladenosine(m6A)modifi-cation plays key roles in various physiological and pathological processes.This review summarizes the recent progress in m6A modification-mediated individual variability in DME expression in terms of the role of m6A modification in regulating basal expression of DMEs,crosstalk between m6A modification and nuclear receptors during the ontogeny of DMEs,and the contribution of m6A modification to xenobi-otic exposure-mediated changes in DME expression.This review aims to provide data for the elucida-tion of individual variations in drug metabolism in clinic.

Large inter-individual and intra-individual differences in the expression and activity of drug-metabolizing enzymes(DMEs)contribute to unpredictable drug response and toxicity,which is a challenge facing precision medicine.Nuclear receptor-mediated transcriptional regulation and epigenetic mechanisms including histone modifications,non-coding RNAs,and DNA methylation can help to explain the individual variability in DME expressions.However,several questions remain unanswered.Recently,epitranscriptomics,an emerging field,provides new insights into the regulation of gene expression.As the most abundant RNA modification in eukaryotes,N6-methyladenosine(m6A)modifi-cation plays key roles in various physiological and pathological processes.This review summarizes the recent progress in m6A modification-mediated individual variability in DME expression in terms of the role of m6A modification in regulating basal expression of DMEs,crosstalk between m6A modification and nuclear receptors during the ontogeny of DMEs,and the contribution of m6A modification to xenobi-otic exposure-mediated changes in DME expression.This review aims to provide data for the elucida-tion of individual variations in drug metabolism in clinic.

Objective:To investigate the clinical effect of "mutual support" framework in costal cartilage rhinoplasty.Methods:From June 2020 to December 2021, the patients were enrolled and undergone rhinoplasty with bilateral lower lateral cartilage margin incision combined with nasal columnar incision in the Department of Plastic & Reconstructive Surgery of Zhejiang Provincial People’s Hospital. During the operation, the sixth costal cartilage was made into the nasal columella support graft(strut) and the nasal tip graft integrated scaffold, and the septal extension grafts (SEG). The strut and SEG were sutured in the same plane to construct the framework to correct the aesthetic defects of the nose. Abode Photoshop CS 6.0 was used to measure a series of aesthetics index before and 6 months after surgery, including nasofrontal angle, nasorostral angle, nasolabial angle, columella lobular angle, ratio of tip projection to the length of the nose and ratio of the length of the infratip lobule to the length of the nasal columella to evaluate the surgical effect. Visual analogue scale (VAS) and rhinoplasty outcome evaluation (ROE) were used to investigate the patients’ satisfaction. Paired t-test was used for data analysis and P<0.05 was considered statistically significant. Results:A total of 53 patients were enrolled, including 4 males and 49 females, aged from 18 to 45 years (average age: 25.6 years). Forty-nine cases were primary rhinoplasty and 4 cases were secondary rhinoplasty. No short-term complications including hemorrhage and infection occurred in 53 patients. All patients were followed up for 6-12 months. There were statistically significant differences in nasofrontal angle, nasorostral angle, nasolabial angle, columella lobular angle, ratio of tip projection to the length of the nose and ratio of the length of the infratip lobule to the length of the nasal columella( P<0.01), which sugguested that aesthetic defects of the nose were corrected and no obvious deflection and rotation of nasal tip occured. VAS score and ROE score postoperatively were 7.6±0.4 and 21.3±2.1, respectively, which were significantly higher than preoperatively( 6.1±0.5, 10.5±1.6)( P< 0.01). Postoperative satisfaction survey showed that swelling disappeared within 4-6 weeks after surgery, and no obvious ventilatory disorder, paresthesia and hyposmia symptoms occurred. Most patients were satisfied with the aesthetic and functional results. Conclusions:The "mutual support" framework in costal cartilage rhinoplasty can reduce the risk of framework deflection and nasal tip rotation and obtain satisfactory nasal columella shape.

Objective:To investigate the clinical effect of "mutual support" framework in costal cartilage rhinoplasty.Methods:From June 2020 to December 2021, the patients were enrolled and undergone rhinoplasty with bilateral lower lateral cartilage margin incision combined with nasal columnar incision in the Department of Plastic & Reconstructive Surgery of Zhejiang Provincial People’s Hospital. During the operation, the sixth costal cartilage was made into the nasal columella support graft(strut) and the nasal tip graft integrated scaffold, and the septal extension grafts (SEG). The strut and SEG were sutured in the same plane to construct the framework to correct the aesthetic defects of the nose. Abode Photoshop CS 6.0 was used to measure a series of aesthetics index before and 6 months after surgery, including nasofrontal angle, nasorostral angle, nasolabial angle, columella lobular angle, ratio of tip projection to the length of the nose and ratio of the length of the infratip lobule to the length of the nasal columella to evaluate the surgical effect. Visual analogue scale (VAS) and rhinoplasty outcome evaluation (ROE) were used to investigate the patients’ satisfaction. Paired t-test was used for data analysis and P<0.05 was considered statistically significant. Results:A total of 53 patients were enrolled, including 4 males and 49 females, aged from 18 to 45 years (average age: 25.6 years). Forty-nine cases were primary rhinoplasty and 4 cases were secondary rhinoplasty. No short-term complications including hemorrhage and infection occurred in 53 patients. All patients were followed up for 6-12 months. There were statistically significant differences in nasofrontal angle, nasorostral angle, nasolabial angle, columella lobular angle, ratio of tip projection to the length of the nose and ratio of the length of the infratip lobule to the length of the nasal columella( P<0.01), which sugguested that aesthetic defects of the nose were corrected and no obvious deflection and rotation of nasal tip occured. VAS score and ROE score postoperatively were 7.6±0.4 and 21.3±2.1, respectively, which were significantly higher than preoperatively( 6.1±0.5, 10.5±1.6)( P< 0.01). Postoperative satisfaction survey showed that swelling disappeared within 4-6 weeks after surgery, and no obvious ventilatory disorder, paresthesia and hyposmia symptoms occurred. Most patients were satisfied with the aesthetic and functional results. Conclusions:The "mutual support" framework in costal cartilage rhinoplasty can reduce the risk of framework deflection and nasal tip rotation and obtain satisfactory nasal columella shape.

Objective:Facial artery is the main blood supply source of facial soft tissue, which has an important influence on facial plastic surgery and injection procedures. There are many types of facial arteries. They have wide coverage, and travel several layers. In this study, the detailed characteristics of the facial arteries were revealed by cadaver dissection.Methods:In 19 donated fresh cranial (28 sides) specimens, the facial arteries were dissected. And then the type, layer, relationship with nasolabial groove, length, diameter, distance from the oral commissure, branches and submental artery were observed and measured.Results:Facial arteries were found in all cadavers, starting from the external carotid arteries, branching submental arteries below the mandibular margins, ascending to the anterior edge of the masseter muscles, crossing the mandibles and entering the faces. After entering into the faces, the facial arteries branched the submental arteries(100%, 28/28), lower labial arteries (100%, 28/28), upper labial arteries (100%, 28/28), lateral nasal arteries (92.9%, 26/28) and the angular arteries (57.2%, 16/28) throughout the courses. According to the vascular route, the facial artery was classified into four types. In TypesⅠ(8 sides), all branches were included and the angular arteries arose directly from the lower segment of the facial arteries (28.6%). In TypesⅡ(8 sides), all branches were included and the angular arteries were the terminal branches (28.6%). In TypesⅢ(10 sides), angular arteries were absent (35.7%). In Type Ⅳ (2 sides), angular arteries and lateral nasal arteries were absent (7.1%). The lower segment of facial artery coursed under the facial expression muscles, and continued to the middle segment at the point which was (26.0±5.0) mm away from the oral commissure on the lateral side. The layer that the facial artery coursed was varied. It passed through the superficial layer of the facial expression muscles. After passing the horizontal line parallel to the lower margin of nasal sill, the upper segment continued to on the superficial layer of the facial expression muscles. The facial arteries were mostly located medial to the nasolabial fold(24 sides, 85.7%) and occasionally across the nasolabial fold(4 sides, 14.3%). The lengths of the upper, middle and lower segments of facial artery were (26.4±10.9) mm, (29.7±8.4) mm, and(33.5±6.9) mm, respectively. The diameters in starting point of upper, middle and lower sections were(2.45±0.48) mm, (1.85±0.12) mm, and (1.09±0.21) mm, respectively. The facial artery passed lateral to the oral commissure and the distance from the intersection of the horizontal line to the oral commissure was (26.0±5.0) mm. The starting point of the superior labial artery locacted below the horizontal line was (8.0±1.4)mm away from the horizontal line of the oral commissure and(55.0±5.2) mm from the mandibular angle. The starting point of the inferior labial artery located below the horizontal line was (17.1±11.1) mm from the horizontal line of the oral commissure, and the distance from the mandibular angle was (44.2±5.2) mm. The diameter of the submental artery in its starting point was (1.4±0.1) mm. The distance from the starting point of the submental artery to the horizontal line of the oral commissure was (34.9±2.6) mm, and the distance from the mandibular angle was (29.4±5.8) mm. The starting point of the submental artery was (6.4±0.8) mm from the lower margin of the mandible. In the midline of the mandible, the distance between the submental artery and the lower margin of the mandible was (9.0±1.0) mm. In the midsagittal plane, the starting point of the submental artery was(8.4±1.0) mm from the lower margin of the mandible.Conclusions:There were several types of facial arteries and the courses were various, but the way they branched and the layers they coursed had certain rules. Understanding the anatomy of facial arteries is helpful to keep the treatment safe.

Objective:Facial artery is the main blood supply source of facial soft tissue, which has an important influence on facial plastic surgery and injection procedures. There are many types of facial arteries. They have wide coverage, and travel several layers. In this study, the detailed characteristics of the facial arteries were revealed by cadaver dissection.Methods:In 19 donated fresh cranial (28 sides) specimens, the facial arteries were dissected. And then the type, layer, relationship with nasolabial groove, length, diameter, distance from the oral commissure, branches and submental artery were observed and measured.Results:Facial arteries were found in all cadavers, starting from the external carotid arteries, branching submental arteries below the mandibular margins, ascending to the anterior edge of the masseter muscles, crossing the mandibles and entering the faces. After entering into the faces, the facial arteries branched the submental arteries(100%, 28/28), lower labial arteries (100%, 28/28), upper labial arteries (100%, 28/28), lateral nasal arteries (92.9%, 26/28) and the angular arteries (57.2%, 16/28) throughout the courses. According to the vascular route, the facial artery was classified into four types. In TypesⅠ(8 sides), all branches were included and the angular arteries arose directly from the lower segment of the facial arteries (28.6%). In TypesⅡ(8 sides), all branches were included and the angular arteries were the terminal branches (28.6%). In TypesⅢ(10 sides), angular arteries were absent (35.7%). In Type Ⅳ (2 sides), angular arteries and lateral nasal arteries were absent (7.1%). The lower segment of facial artery coursed under the facial expression muscles, and continued to the middle segment at the point which was (26.0±5.0) mm away from the oral commissure on the lateral side. The layer that the facial artery coursed was varied. It passed through the superficial layer of the facial expression muscles. After passing the horizontal line parallel to the lower margin of nasal sill, the upper segment continued to on the superficial layer of the facial expression muscles. The facial arteries were mostly located medial to the nasolabial fold(24 sides, 85.7%) and occasionally across the nasolabial fold(4 sides, 14.3%). The lengths of the upper, middle and lower segments of facial artery were (26.4±10.9) mm, (29.7±8.4) mm, and(33.5±6.9) mm, respectively. The diameters in starting point of upper, middle and lower sections were(2.45±0.48) mm, (1.85±0.12) mm, and (1.09±0.21) mm, respectively. The facial artery passed lateral to the oral commissure and the distance from the intersection of the horizontal line to the oral commissure was (26.0±5.0) mm. The starting point of the superior labial artery locacted below the horizontal line was (8.0±1.4)mm away from the horizontal line of the oral commissure and(55.0±5.2) mm from the mandibular angle. The starting point of the inferior labial artery located below the horizontal line was (17.1±11.1) mm from the horizontal line of the oral commissure, and the distance from the mandibular angle was (44.2±5.2) mm. The diameter of the submental artery in its starting point was (1.4±0.1) mm. The distance from the starting point of the submental artery to the horizontal line of the oral commissure was (34.9±2.6) mm, and the distance from the mandibular angle was (29.4±5.8) mm. The starting point of the submental artery was (6.4±0.8) mm from the lower margin of the mandible. In the midline of the mandible, the distance between the submental artery and the lower margin of the mandible was (9.0±1.0) mm. In the midsagittal plane, the starting point of the submental artery was(8.4±1.0) mm from the lower margin of the mandible.Conclusions:There were several types of facial arteries and the courses were various, but the way they branched and the layers they coursed had certain rules. Understanding the anatomy of facial arteries is helpful to keep the treatment safe.

OBJECTIVE: To explore the molecular basis for an individual with postnatal deafness and provide genetic counseling for her family. METHODS: Following extraction of genomic DNA from peripheral blood samples, 127 genes associated with deafness were subjected to targeted capturing and next generation sequencing. Suspected mutation was verified by Sanger sequencing. RESULTS: The proband was found to carry a homozygous c.1893C>A mutation in the TECTA gene, which is located in the tectorial membrane of inner ear and may cause premature termination of translation of TECTA protein. In addition, two heterozygous mutations, c.13010C>T and c.12790G>A, were found in the USH2A gene. Whilst the former is likely to be pathogenic, the latter has unknown clinical significance. Further analysis suggested that all three mutations have derived from the parents of the proband. CONCLUSION The homozygous c.1893C>A mutation of the TECTA gene probably underlies the proband's hearing loss which conformed to an autosomal recessive inheritance.
Deafness ; Extracellular Matrix Proteins ; genetics ; Female ; GPI-Linked Proteins ; genetics ; High-Throughput Nucleotide Sequencing ; Homozygote ; Humans ; Mutation ; Pedigree

OBJECTIVE: To explore the genetic basis for a patient with syndromic hearing loss. METHODS: Genomic DNA of the patient was extracted, for which 127 deafness-related genes were enriched with a chip. Following next generation sequencing, pathogenic loci in exonic regions were analyzed through comparison against the databases. Genotype of her fetus for the suspected site was determined by testing the amniotic fluid sample. qPCR method was applied to verify the deletion of a large fragment. RESULTS: The proband was diagnosed with Waardenburg syndrome type 2, and had harbored a novel heterozygous deletion of the exons 3 and 4 of the SOX10 gene. Her fetus was found to carry the same deletion and presented with blue eyes and deafness after birth. CONCLUSION Waardenburg syndrome type 2 due to SOX10 gene deletion may feature autosomal dominant inheritance with incomplete penetrance. The deletion of exons 3 and 4 of the SOX10 gene probably underlies the disease in this family.
Eye Color ; Female ; Hearing Loss ; Humans ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; SOXE Transcription Factors ; genetics ; Waardenburg Syndrome

OBJECTIVETo explore the origin of a supernumerary small marker chromosome (sSMC) in a fetus, and to assess the feasibility of single nucleotide polymorphism array (SNP-array) for prenatal diagnosis.

METHODSThe fetal sample was subjected to karyotyping analysis. The identified sSMC was subjected to genome-wide scan using a SNP microarray chip. The results were validated with fluorescence in situ hybridization (FISH).

RESULTSThe karyotype of the fetus was determined as 47,XX,+mar, which was verified by SNP microarray chip analysis as a 34.6 Mb duplication in 12p13.33p11.1. FISH analysis confirmed that the sSMC has originated from chromosome 12p.

CONCLUSIONThe karyotype of the fetus was determined as 47,XX,+i(12)(p10). Tetrasomy 12p is reported to be a marker for Pallister-Killian syndrome, which may result in multi-system anomalies. SNP-array analysis can simultaneously detect microdeletions and microduplications, which may be used for prenatal diagnosis of suspected cases.

Adult ; Chromosome Aberrations ; Chromosome Banding ; Chromosome Disorders ; diagnostic imaging ; embryology ; genetics ; Chromosomes, Human, Pair 12 ; genetics ; Female ; Fetus ; abnormalities ; diagnostic imaging ; metabolism ; Genome-Wide Association Study ; methods ; Humans ; In Situ Hybridization, Fluorescence ; Karyotype ; Karyotyping ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide ; Pregnancy ; Ultrasonography, Prenatal ; methods

OBJECTIVETo explore the genetic causes for a child with multiple congenital malformations and epilepsy through analysis of copy number variations, and to correlate the genotype with the phenotype.

METHODSG-banding karyotyping was performed on the child and her parents. Single nucleotide polymorphisms array (SNP-array) was used to map the exact chromosomal breakpoints in the proband. The result was validated with fluorescence in situ hybridization (FISH).

RESULTSG banding analysis suggested that the proband had a karyotype of 46,XX,del(4)(p15), while both of his parents had a normal karyotype. SNP-array has identified a hemizygous deletion of 13.3 Mb on chromosome 4p16.3p15.33, which has been implicated in Wolf-Hirschhorn syndrome. FISH assay has confirmed the de novo origin of the deletion, with the karyotype and clinical phenotype of both parents taken into consideration.

CONCLUSIONA case of Wolf-Hirschhorn syndrome has been diagnosed by clinical manifestation and karyotyping analysis. Compared with conventional karyotyping analysis, SNP-array has greater resolution and accuracy, and can provide useful information for genetic counseling.

Chromosome Banding ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant, Newborn ; Karyotyping ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Wolf-Hirschhorn Syndrome ; genetics