Early exposure to infections increases the risk of allergic rhinitis-a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to provide evidence for early life care by meta-analyzing the relationship between infection during pregnancy and up to 2 years of age and the risk of subsequent allergic rhinitis (AR). METHODS: Published studies up to April 2022 were systematically searched in PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang Database, and VIP. Literature screening, including quality assessment, was performed, and the effect values (OR, HR, RR) and 95% confidence intervals (95% CI) of infection during pregnancy and up to 2 years of age and allergic rhinitis were extracted from each qualified study. RESULTS: In total, 5 studies with a sample size of 82,256 reported the relationship between infection during pregnancy and offspring AR. Meta-analysis showed that maternal infection during pregnancy was associated with an increased risk of childhood AR in offspring (OR = 1.34, 95% CI: 1.08-1.67). Altogether, 13 studies with a sample size of 78,426 reported evidence of an association between infection within 2 years of age and subsequent AR in children. A pooled meta-analysis of all studies showed that early infection within 2 years of age was closely associated with childhood AR (OR = 1.25, 95% CI: 1.12-1.40), especially upper respiratory tract infection (OR = 1.32, 95% CI: 1.06-1.65) and gastrointestinal infections (OR = 1.37, 95% CI: 1.01-1.86), but ear infection showed similar results in the cohort study (OR = 1.13, 95% CI: 1.04-1.22). CONCLUSION: Current evidence suggests that infection during pregnancy, early upper respiratory infection, gastrointestinal infections and ear infection within 2 years of age would increase the risk of AR in children. Therefore, the prevention of infection during pregnancy and in infancy and young children needs to be emphasized.

Paternal Programming of Liver Function and Lipid Profile Induced by a Paternal Pre-Conceptional Unhealthy Diet: Potential Association with Altered Gut Microbiome Composition.

BACKGROUND/AIMS: Paternal exposure to adverse environmental conditions can act on offspring's phenotype and influence offspring's later life disease risk. Our study was designed to examine the effect of feeding male rats before mating a high-fat, high-sucrose and high-salt diet (HFSSD) over two generations (F0 and F1) on their offspring's (F2) liver function and gut microbiome composition. METHODS: Male F0 rats and male F1 rats were fed either control diet or HFSSD before mating. Liver function of F2 offspring was investigated, and their gut microbiome composition was analyzed by 16S rRNA gene sequencing in the F2 offspring of rats whose fathers and grandfathers were fed with control diet (CD) (F0CD+F1CD-F2 group) or HFSSD prior to mating (F0HD+F1HD-F2 group). RESULTS: F2 offspring had higher serum aspartate aminotransferase activity (female, p < 0.05 and male, p < 0.01 respectively) compared with control. Shannon indexes of gut microbiota indicated a significantly higher diversity in the female F0HD+F1HD-F2 as compared to F0CD+F1CD-F2 female offspring (p < 0.01). The dominant phyla of all the groups were Bacteroidetes, Firmicutes and Proteobacteria. There were significant differences in gut bacterial community composition at phyla and genus level between the F0CD+F1CD-F2 and F0HD+F1HD-F2. Furthermore, the variation in the relative abundance (percentage) of bacterial genus in the F2 offspring was associated with liver function alterations induced by a paternal pre-conceptional unhealthy diet. Male F0HD+F1HD-F2 offspring had higher serum cholesterol, high density lipoproteins as well as low density lipoproteins concentrations compared to the corresponding male control rats. CONCLUSION: Taken together, our findings suggested that a paternal pre-conceptional unhealthy diet predisposes the offspring to mild liver function alterations and alterations of gut microbiota in later life. Effects on lipids were sex-specific and only seen in male offspring.

BMP4: a Possible Key Factor in Differentiation of Auditory Neuron-Like Cells from Bone-Derived Mesenchymal Stromal Cells.

BACKGROUND: Previous studies have shown that BMP4 may play an important part in the development of auditory neurons (ANs), which are degenerated in sensorineural hearing loss. However, whether BMP4 can promote sensory fate specification from mesenchymal stromal cells (MSCs) is unknown so far. METHODS: MSCs isolated from Sprague-Dawley (SD) rats were confirmed by expression of MSC markers using flow cytometry and adipogenesis/osteogenesis using differentiation assays. MSCs treated with a complex of neurotrophic factors (BMP4 group and non-BMP4 group) were induced into auditory neuron-like cells, then the differences between the two groups were analyzed in morphological observation, cell growth curve, qRT-PCR, and immunofluorescence. RESULTS: Flow cytometric analysis showed that the isolated cells expressed typical MSC surface markers. After adipogenic and osteogenic induction, the cells were stained by oil red O and Alizarin Red. The neuronal induced cells were in the growth plateau and had special forms of neurons. In the presence of BMP4, the inner ear genes NF-M, Neurog1, GluR4, NeuroD, Calretinin, NeuN, Tau, and GATA3 were up-regulated in MSCs. CONCLUSIONS: MSCs have the capacity to differentiate into auditory neuron-like cells in vitro. As an effective inducer, BMP4 may play a key role in transdifferentiation.

The impact of umbilical blood flow regulation on fetal development differs in diabetic and non-diabetic pregnancy.

BACKGROUND/AIMS: Diabetes is well-known to influence endothelial function. Endothelial function and blood flow regulation might be different in diabetic and non-diabetic pregnancy. However, the impact of umbilical blood flow regulation in gestational diabetes on fetal development is unknown so far. METHODS: In a prospective birth cohort study, we analyzed the association of the umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) and fetal size measures (biparietal diameter, head circumference, abdominal circumference, femur length and birth weight) in 519 non-gestational diabetes mellitus pregnancies (controls) and 226 gestational diabetes mellitus pregnancies in middle (day 160.32 ±16.29 of gestation) and late (day 268.12 ±13.04 of gestation) pregnancy. RESULTS: Multiple regression analysis considering confounding factors (gestational day of ultrasound examination, offspring sex, maternal body mess index before pregnancy, maternal age at delivery, maternal body weight at delivery and maternal hypertension) showed that umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) were associated with fetal head circumference and femur length in middle gestational diabetes mellitus pregnancy but not in non-gestational diabetes mellitus pregnancy. Head circumference, biparietal diameter, abdominal circumference and femur length in mid gestation were smaller in fetus of gestational diabetes mellitus pregnancy versus non-gestational diabetes mellitus pregnancy. In contrast to non-gestational diabetes mellitus pregnancy in late gestation, umbilical artery Doppler indices in gestational diabetes mellitus pregnancy were not associated with ultrasound measures of fetal growth. Birth weight was slightly increased in gestational diabetes mellitus pregnancy as compared to non-gestational diabetes mellitus pregnancy. CONCLUSIONS: The impact of umbilical blood flow on fetal growth is time dependent in human gestational diabetes mellitus and non-gestational diabetes mellitus pregnancy. In gestational diabetes mellitus pregnancy umbilical blood flow is critical for organ development in much earlier stages of pregnancy as compared to non-gestational diabetes mellitus pregnancy. The physiological and molecular pathways why there is a catch up growth in later times of gestational diabetes mellitus pregnancy resulting in larger gestational diabetes mellitus babies at birth needs to be addressed in further studies.

Polyphase exhumation in the western Qinling Mountains, China: Rapid Early Cretaceous cooling along a lithospheric-scale tear fault and pulsed Cenozoic uplift.

The western sector of the Qinling-Dabie orogenic belt plays a key role in both Late Jurassic to Early Cretaceous "Yanshanian" intracontinental tectonics and Cenozoic lateral escape triggered by India-Asia collision. The Taibai granite in the northern Qinling Mountains is located at the westernmost tip of a Yanshanian granite belt. It consists of multiple intrusions, constrained by new Late Jurassic and Early Cretaceous U-Pb zircon ages (156 ± 3 Ma and 124 ± 1 Ma). Applying various geochronometers (40Ar/39Ar on hornblende, biotite and K-feldspar, apatite fission-track, apatite [U-Th-Sm]/He) along a vertical profile of the Taibai Mountain refines the cooling and exhumation history. The new age constraints record the prolonged pre-Cenozoic intracontinental deformation as well as the cooling history mostly related to India-Asia collision. We detected rapid cooling for the Taibai granite from ca. 800 to 100 °C during Early Cretaceous (ca. 123 to 100 Ma) followed by a period of slow cooling from ca. 100 Ma to ca. 25 Ma, and pulsed exhumation of the low-relief Cretaceous peneplain during Cenozoic times. We interpret the Early Cretaceous rapid cooling and exhumation as a result from activity along the southern sinistral lithospheric scale tear fault of the recently postulated intracontinental subduction of the Archean/Palaeoproterozoic North China Block beneath the Alashan Block. A Late Oligocene to Early Miocene cooling phase might be triggered either by the lateral motion during India-Asia collision and/or the Pacific subduction zone. Late Miocene intensified cooling is ascribed to uplift of the Tibetan Plateau.

Unravelling the history of mountain belts through U-Pb and Lu-Hf dating of zircon and 40Ar/39Ar dating of detrital white mica: a case study from the Eastern Alps.

Radiogenic isotopes of igneous and detrital minerals from various clastic rocks of mountain belts are used to reveal tectonic and sedimentary processes, which are otherwise difficult to detect. Here, we discuss the results of U-Pb and Lu-Hf zircon systems, and 40Ar/39Ar on detrital white mica in Eastern Alps. Zircon and white mica are chemically and mechanically stable and occur in magmatic, metamorphic and sedimentary rocks. During subsequent metamorphism, zircon is resistant against high temperature, >650 °C (U-Pb) and 900 °C (Lu-Hf). The Lu-Hf zircon system is used as a tracer of initial magma separation from the mantle, and the U-Pb zircon system records magmatic crystallization. The 40Ar/39Ar white mica system is stable up to 400-450 °C dating either formation or cooling after high-grade metamorphism. Detrital U-Pb zircon ages on two major rivers draining the Eastern Alps do not record any sign of Alpine orogeny or metamorphism. Consequently, U-Pb zircon studies can entirely miss the record of collisional orogeny in cool, magma-poor collision orogens. In contrast, 40Ar/39Ar white mica ages record Early and Late Alpine metamorphism but are limited to revealing the pre-orogenic history. U-Pb zircon and 40Ar/39Ar white mica yield different information in provenance studies. In the Eastern Alps, U-Pb zircon dating of magmatic and clastic rocks indicates intense formation of magmatic rocks between 630 and 230 Ma. Felsic rocks dominate the older age groups, and increasingly young mafic rocks were dated, specifically between 265 and 230 Ma. Hf isotopes record increasing juvenile input since ∼630 Ma. Two different groups with respect to Mesoproterozoic depleted mantle ages are shown: (1) one group with a Mesoproterozoic age gap typical for Gondwana-derived units, and (2) a rare group with Mesoproterozoic ages recording a new tectonic element in the Austroalpine basement in Alps.

Unveiling the hidden risk: paternal smoking and alcohol exposure prior to conception as independent factors for allergic rhinitis in children.

Introduction: Limited knowledge exists regarding the impact of paternal smoking and alcohol exposure on the development of allergic rhinitis in offspring. Our study aimed to investigate the potential association between preconception paternal smoking and alcohol exposure and the likelihood of children allergic rhinitis. Methods: A retrospective case-control study of 556 prepubertal children aged 3-12 years was performed. The participants were 278 children with allergic rhinitis and 278 healthy controls matched for age and gender. Self-administered questionnaires were distributed and collected on-site, focusing on various factors related to the children's fathers, mothers, and the children themselves during the first year of life and the past 12 months, from March to October 2022. Results: Multivariate analysis demonstrated that paternal smoking, paternal alcohol consumption prior to conception, paternal allergic diseases, children with a family history of allergies, maternal allergic diseases and pregnancy complications were identified as independent risk factors for allergic rhinitis in their offspring. Moreover, after considering confounding factors, it was observed that paternal smoking exceeding 5 cigarettes per day in the year preceding pregnancy and exceeding 11 years significantly elevated the likelihood of allergic rhinitis in children (OR = 2.009 and 2.479, respectively). Furthermore, the consumption of alcohol by the father at intervals of less than one month in the year prior to pregnancy and a duration of alcohol consumption exceeding 11 years prior to pregnancy are both associated with a significantly increased risk of allergic rhinitis in children (OR = 2.005 and 3.149, respectively). Conclusions: Paternal smoking and alcohol consumption prior to conception contribute to an increased risk of allergic rhinitis in children, with the risk being dependent on the dosage and duration of exposure. Therefore, it is important to not only focus on personal and maternal environmental exposures when considering the occurrence risk of allergic rhinitis in children, but also to consider paternal detrimental exposures prior to conception.

A functional fetal HSD11B2[CA]n microsatellite polymorphism is associated with maternal serum cortisol concentrations in pregnant women.

BACKGROUND/AIMS: Cortisol plays an important role during pregnancy. It controls maternal glucose metabolism and fetal development. Cortisol metabolism is partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and human placenta. The activity of the enzyme is partially controlled by functional polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this functional gene polymorphism on cortisol metabolism and potential effects on the newborn's is unknown so far. METHODS: In the current prospective birth cohort study in southern Asia, we analyzed the association of the HSD11B2[CA]n microsatellite polymorphisms in 187 mothers and their newborn's on maternal and newborn's serum cortisol concentrations. RESULTS: Using multivariable regression analyses considering known confounding (gestational age, newborn's gender, the labor uterine contraction states and the timing during the day of blood taking), we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first intron was related to maternal cortisol concentration (R2=0.26, B=96.27, p=0.007), whereas as the newborn's cortisol concentrations were independent of fetal and maternal HSD11B2[CA]n microsatellite polymorphism. CONCLUSIONS: Our study showed for the first time that the fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration. This indicates that fetal genes controlling cortisol metabolism may affect maternal cortisol concentration and hence physiology in healthy pregnant women.

Exploratory study of a multifrequency EIT-based method for detecting intracranial abnormalities.

Objective: The purpose of this paper is to compare the differences in the features of multifrequency electrical impedance tomography (MFEIT) images of human heads between healthy subjects and patients with brain diseases and to explore the possibility of applying MFEIT to intracranial abnormality detection. Methods: Sixteen healthy volunteers and 8 patients with brain diseases were recruited as subjects, and the cerebral MFEIT data of 9 frequencies in the range of 21 kHz - 100 kHz of all subjects were acquired with an MFEIT system. MFEIT image sequences were obtained according to certain imaging algorithms, and the area ratio of the ROI (AR_ROI) and the mean value of the reconstructed resistivity change of the ROI (MVRRC_ROI) on both the left and right sides of these images were extracted. The geometric asymmetry index (GAI) and intensity asymmetry index (IAI) were further proposed to characterize the symmetry of MFEIT images based on the extracted indices and to statistically compare and analyze the differences between the two groups of subjects on MFEIT images. Results: There were no significant differences in either the AR_ROI or the MVRRC_ROI between the two sides of the brains of healthy volunteers (p > 0.05); some of the MFEIT images mainly in the range of 30 kHz - 60 kHz of patients with brain diseases showed stronger resistivity distributions (larger area or stronger signal) that were approximately symmetric with the location of the lesions. However, statistical analysis showed that the AR_ROI and the MVRRC_ROI on the healthy sides of MFEIT images of patients with unilateral brain disease were not significantly different from those on the affected side (p > 0.05). The GAI and IAI were higher in all patients with brain diseases than in healthy volunteers except for 80 kHz (p < 0.05). Conclusion: There were significant differences in the geometric symmetry and the signal intensity symmetry of the reconstructed targets in the MFEIT images between healthy volunteers and patients with brain diseases, and the above findings provide a reference for the rapid detection of intracranial abnormalities using MFEIT images and may provide a basis for further exploration of MFEIT for the detection of brain diseases.

Cesarean section and the risk of allergic rhinitis in children: a systematic review and meta-analysis.

Multiple evidence indicates that perinatal factors make impact on immune development and affect offspring allergic rhinitis (AR) risk. In this systematic review and meta-analysis, we examined available published studies to clarify the relationship between cesarean section (C-section) and offspring AR in children. To explore the relationship between C-section, especially the special attention was paid to different cesarean delivery mode, and the risk of AR in children. Articles were searched using PubMed, Web of Science, EMBASE, Cochrane Library, China knowledge Network, Wanfang, and China Science and Technology Journal databases. A meta-analysis of 22 studies published before August 1, 2022, which included 1,464,868 participants, was conducted for statistical analysis with RevMan5.4. The correlation strength between C-section and offspring AR was determined by combining odds ratio (OR) and 95% confidence interval (95% CI). Meta-regression and subgroup analyses were used to explore potential sources of heterogeneity. Publication bias was detected using the funnel chart and Egger tests. Meta-analysis revealed that there was a significant correlation between C-section and children AR (OR = 1.19, 95% CI: 1.12-1.27, P < 0.001), especially C-section with a family history of allergy (OR = 1.82, 95% CI: 1.36-2.43, P < 0.001). Moreover, elective C-section (without genital tract microbe exposure) had the higher risk of offspring AR (OR = 1.24, 95% CI: 1.05-1.46, P = 0.010) compared with the whole study. Meta-regression demonstrated that sample size explained 38.0% of the variability between studies, and year of publication explained 18.8%. Delivery by C-section, particularly elective C-section and C-section with a family history of allergy can increase the risk of AR in children.

Application value of a computer-aided diagnosis and management system for the detection of lung nodules.

Background: Computer-aided diagnosis (CAD) systems can help reduce radiologists' workload. This study assessed the value of a CAD system for the detection of lung nodules on chest computed tomography (CT) images. Methods: The study retrospectively analyzed the CT images of patients who underwent routine health checkups between August 2019 and November 2019 at 3 hospitals in China. All images were first assessed by 2 radiologists manually in a blinded manner, which was followed by assessment with the CAD system. The location and classification of the lung nodules were determined. The final diagnosis was made by a panel of experts, including 2 associate chief radiologists and 1 chief radiologist at the radiology department. The sensitivity for nodule detection and false-positive nodules per case were calculated. Results: A total of 1,002 CT images were included in the study, and the process was completed for 999 images. The sensitivity of the CAD system and manual detection was 90.19% and 49.88% (P<0.001), respectively. Similar sensitivity was observed between manual detection and the CAD system in lung nodules >15 mm (P=0.08). The false-positive nodules per case for the CAD system were 0.30±0.84 and those for manual detection were 0.24±0.68 (P=0.12). The sensitivity of the CAD system was higher than that of the radiologists, but the increase in the false-positive rate was only slight. Conclusions: In addition to reducing the workload for medical professionals, a CAD system developed using a deep-learning model was highly effective and accurate in detecting lung nodules and did not demonstrate a meaningfully higher the false-positive rate.

Association of fetal but not maternal P-glycoprotein C3435T polymorphism with fetal growth and birth weight, a possible risk factor for cardiovascular diseases in later life.

BACKGROUND: The multidrug transporter P-glycoprotein (PGP) is expressed in the human placenta. In particular the C3435T ABCB1 polymorphism was associated with altered tissue expression of PGP in the human placenta. However, the potential functional impact of this polymorphism on the offspring is unknown so far. METHODS: We analyzed the impact of the ABCB1/C3435T polymorphism on fetal growth in 262 mother/child pairs. Fetal growth was assessed by differential ultrasound examination of the fetal body prior to birth and by measuring birth weight. RESULTS: The maternal ABCB1/C3435T polymorphism showed no trend for an association with birth weight or any ultrasound parameter describing late gestational fetal body shape. Genotyping the newborns, however, demonstrated that newborns carrying two copies of the T allele had a birth weight of 3176.39 g, whereas CT and CC newborns had a birth weight of 3345.04 g (p = 0.022). Adjusting for gestational age at delivery, child's gender, maternal BMI, maternal age and body weight at delivery confirmed this finding (p = 0.009). Considering gestational day of late ultrasound examination, gestational age at delivery, child's gender, maternal BMI, maternal age and maternal body weight at delivery, the fetal ABCB1/C3435T genotype revealed likewise a significant negative correlation with abdominal diameter and abdominal circumference (R2 = 0.538, p = 0.010 and R2 = 0.534, p = 0.005, respectively). CONCLUSIONS: Low birth weight may be a risk factor for cardiovascular diseases in later life. The fetal ABCB1/C3435T gene polymorphism may contribute to this risk. Since PGP controls transport of various biological agents, we suggest that PGP is involved in the transport of biological agents to the fetus that are important for normal fetal growth.

Fabrication and Performance of UV Photodetector of ZnO Nanorods Decorated with Al Nanoparticles.

In this work, localized surface plasmon resonance (LSPR) mediated by aluminum nanoparticles (Al NPs) was investigated to enhance the ultraviolet (UV) response of the zinc oxide nanorods (ZnO NRs) grown by the hydrothermal method. The ZnO NRs were characterized by scanning electron microscope, energy dispersive spectroscopy, X-ray diffractometer, Raman spectrometer, ultraviolet-visible spectrophotometer and fluorescence spectrometer. The results show that the morphology and crystalline structure of the ZnO NRs could not be changed before and after decoration with Al NPs, but the absorption rates in the UV range and the photoluminescence (PL) properties were improved. The photo-to-dark current ratio of ZnO NRs with Al NPs was about 447 for 325 nm UV light (5 mW/cm2) at 3.0 V bias, with the sensitivity increasing from 9.5 to 47.8, and the responsivity increasing from 53 to 267 mA/W.

Maternal tobacco exposure during pregnancy and allergic rhinitis in offspring: A systematic review and meta-analysis.

BACKGROUND: Maternal tobacco exposure during pregnancy is known to cause a potential hazard to the offspring's health. So far, published studies have shown no consistent results with whether tobacco exposure in utero is causally linked to the development of allergic rhinitis in offspring. The aim of this study was to comprehensively evaluate the association between maternal tobacco exposure during pregnancy and allergic rhinitis in offspring by meta-analysis and to provide reference for clinical work. METHODS: Literatures were searched in CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of science and Embase up to September 30,2020. Screening, inclusion, quality assessment, data extraction and data analysis of the literatures were conducted. Meta-analysis was performed with Revman 5.3 and State15.1 software. Odds ratio (OR) and 95%CI were used as observation indicators. RESULTS: We had retrieved 16 articles with 22 independent datasets and 11,49,879 sample size. When all the studies were analyzed together, the results showed that maternal smoking exposure during pregnancy would increase the risk of allergic rhinitis in offspring (OR = 1.13, 95%CI:1.02-1.26), especially maternal passive smoking during pregnancy (OR = 1.39, 95%CI:1.05-1.84). But subgroup analysis showed that maternal active smoking during pregnancy was only significantly associated with offspring allergic rhinitis in cross-sectional studies (OR = 1.24, 95%CI:1.07-1.45) and study done in America study (OR = 1.22, 95%CI:1.05-1.42). CONCLUSIONS: Tobacco exposure during pregnancy could increase the risk of allergic rhinitis in offspring. The importance of avoiding prenatal tobacco exposure should be emphasized more for the health of next generation in the public.

Congenital Middle Ear Malformation with Common Deafness Gene Mutation Analysis: A Review of 813 Profound Sensorineural Hearing Loss Child Patients.

Deafness gene variants play a key role in inner ear malformations. However, the relationship between congenital middle ear malformations and common deafness genes (GJB2, SLC26A4, and mtDNA) in profound sensorineural hearing loss (SNHL) child patients remains poorly investigated. Here we showed that there was no statistical significance in the total mutation frequency of the three common deafness genes in the middle ear malformation group (21.2%, 41/193) in comparison with the normal middle ear and inner ear group (21.0%, 116/553) (χ2 = 0.0061, p = 0.940). Moreover, the mutation ratio of GJB2 and SLC26A4 in the middle ear malformation group (18.7%, 36/193; 2.6%, 5/193) was not significantly different from that in the normal middle ear and inner ear group (17.7%, 98/553; 2.4%, 13/553) (χ2 = 0.084, p = 0.772; χ2 = 0.0000, p = 1.000). The mutation ratio of GJB2 235delC and GJB2 79G>A in the middle ear malformation group (8.8%, 17/193; 8.8%, 17/193) was almost the same to that in the normal middle ear and inner ear group (8.6%, 48/553; 6.7%, 37/553) (χ2 = 0.0030, p = 0.957; χ2 = 0.9556, p = 0.328). The high jugular bulb subgroup analysis also showed the same results. Our findings suggested that GJB2, SLC26A4, and mtDNA mutations might not be related to the middle ear malformations in profound SNHL child patients. Anat Rec, 303:594-599, 2020. © 2019 American Association for Anatomy.

The Relationship Between Single Nucleotide Polymorphisms of SMAD3/SMAD6 and Risk of Esophageal Squamous Cell Carcinoma in Chinese Population.

BACKGROUND: The TGF-ß signal pathways play a key role in the development and promotion of squamous cell carcinoma (SCC). The pathway is mediated by the SMAD family proteins that include SMAD3 and SMAD6. Our study aimed to evaluate the relationship between single nucleotide polymorphism (SNP) of SMAD3/SMAD6 and susceptibility to esophageal squamous cell carcinoma (ESCC) in the Chinese population. PATIENTS AND METHODS: This was a hospital-based case-control study compromised of 1043 ESCC patients and 1315 non-cancer patients. Seven SMAD3/SMAD6 (rs8028147, rs3743343, rs3743342, rs8025774, rs8031440, rs803167, and rs34643453) SNPs were selected and used to evaluate their correlation with ESCC susceptibility. Genetic model tests, stratified analyses, linkage disequilibrium analyses, and haplotype analyses were performed in our study. RESULTS: Participants with SMAD3 rs3743342 C>T, rs8025774 C>T, rs8031440 G>A or rs8031627 G>A had a significantly higher risk of ESCC. This was more evident in males, older patients (>63 years), smokers, and non-alcohol drinking participants. Linkage disequilibrium analyses further revealed that there were strong correlations between SMAD3 rs3743342 C>T, rs8025774 C>T, rs8031440 G>A, and rs8031627 G>A. In the same line, haplotype analyses revealed that SMAD3 ACCCGGSMAD6A and SMAD3AGCCGGSMAD6A were associated with less susceptibility to ESCC while SMAD3ATTTAASMAD6A was associated with a higher risk of ESCC. CONCLUSION: SNPs of SMAD3 were related to higher susceptibility to ESCC. As such, they may contribute to the development of viable strategies for early diagnosis and treatment of ESCC. However, more detailed association mechanisms between SMAD3/SMAD6 SNPs and ESCC need further experiments to prove.

Efficient introduction of an isogenic homozygous mutation to induced pluripotent stem cells from a hereditary hearing loss family using CRISPR/Cas9 and single-stranded donor oligonucleotides.

BACKGROUND: Heterozygous purinergic receptor p2x gene ( P2RX2) c.178G>T (p.V60L) mutations can lead to progressive hearing loss (HL) and increased susceptibility to noise. However, the underlying mechanisms remain unclear. A combination of human induced pluripotent stem cell (hiPSC) technology with clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)9-mediated gene editing may provide a promising tool to study gene function and treat hereditary deafness in humans. METHODS: hiPSC technology and CRISPR/Cas9-mediated gene editing were used to generate heterozygous and homozygous P2RX2 c.178G>T (p.V60L) cell models. RESULTS: We generated non-integrative hiPSCs from urine samples derived from three members of a large Chinese family carrying heterozygous P2RX2 c.178G>T mutations (designated P2RX2+/-) as a model to study P2RX2-mediated hereditary HL. Furthermore, we used CRISPR/Cas9 and single-stranded donor oligonucleotides to genetically establish homozygous P2RX2 c.178G>T hiPSCs (designated P2RX2-/-) from heterozygous patient-specific hiPSCs as a control to further study the pathological gene function. CONCLUSIONS: Heterozygous and homozygous P2RX2-mutated hiPSC lines are good models to investigate the pathological mechanisms of P2RX2 mutations in HL pathogenesis. Our findings confirmed our hypothesis that it is feasible and convenient to introduce precise point mutations into genomic loci of interest to generate gene-mutated hiPSC models.

A novel frameshift mutation of SMPX causes a rare form of X-linked nonsyndromic hearing loss in a Chinese family.

X-linked hearing impairment is the rarest form of genetic hearing loss (HL) and represents only a minor fraction of all cases. The aim of this study was to investigate the cause of X-linked inherited sensorineural HL in a four-generation Chinese family. A novel duplication variant (c.217dupA, p.Ile73Asnfs*5) in SMPX was identified by whole-exome sequencing. The frameshift mutation predicted to result in the premature truncation of the SMPX protein was co-segregated with the HL phenotype and was absent in 295 normal controls. Subpopulation screening of the coding exons and flanking introns of SMPX was further performed for 338 Chinese patients with nonsydromic HL by Sanger sequencing, and another two potential causative substitutions (c.238C>A and c.55A>G) in SMPX were identified in additional sporadic cases of congenital deafness. Collectively, this study is the first to report the role of SMPX in Chinese population and identify a novel frameshift mutation in SMPX that causes not only nonsyndromic late-onset progressive HL, but also congenital hearing impairment. Our findings extend the mutation and phenotypic spectrum of the SMPX gene.

The role of transcription factors of neurosensory cells in non-syndromic sensorineural hearing loss with or without inner ear malformation.

CONCLUSIONS: Previous studies have stated the roles and correlation of the four TFs (Sox2, Atoh1, Neurog1, and Neurod1) in the development of neurosensory cells. but whether they are inherited pathogenic factors to cause non-syndromic sensorineural hearing loss is unknown so far. This is the first time for screening the Sox2, Atoh1, Neurog1, and Neurod1 genes in children with NSHL. The c.133A > G in Neurod1 gene is a polymorphism, which is not associated with NSHL. Although these genes are the recognized TFs for modulating the development and transformation of NSCs, they may not be the inherited pathogenic factors to cause congenital severe or profound NSHL directly. OBJECTIVE: To investigate the effect of the transcription factors (TFs) for the development of neurosensory cells (NSCs) and to explore the genetic etiology of congenital profound non-syndromic sensorineural hearing loss (NSHL). METHODS: Children with NSHL, from multi-national and regional group, and control group were recruited to screen for the most common mutations for non-syndromic deafness among East Asian (mtDNA 12S rRNA: 1555A > G, 1494C > T; SLC26A4: IVS7-2 A > G, 2168 C > T). And mutational analysis of the coding regions in Sox2, Atoh1 and Neurog1, Neurod1 genes were performed. RESULTS: Only the c.133A > G (p. Ala45Thr) in the Neurod1 gene was detected in this study. The allele frequencies of this variant were 88.00% and 84.88% in the inner ear malformation group and the normal inner ear group, respectively, while 90.85% of children in the control group carried c.133A > G. This variant existed in every group commonly and had no significant difference among them. No variant in the other two TFs was detected in this cohort.

[Advances in diagnosis and treatment of Meniere's disease].

Meniere's disease (MD), a kind of common disease of otology, is based on the endolymphatic hydrops. The clinical features of MD are intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus and ear fullness. With the in-depth exploration of the disease, the diagnosis and treatment of MD has made a series of research results. In this paper, the related literature and research reports in recent years were reviewed.