Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective:To explore the effect of transcutaneous electrical nerve stimulation (TENS) on interleukin-33 (IL-33)/growth stimulation expressed gene 2 (ST2) signaling pathway in the dorsal root ganglia (DRGs) of rats modeling hyperalgesia (HP).Methods:This study consisted of two experiments. In the first, 30 Sprague-Dawley (SD) rats were randomly divided into a blank group, a Sham-HP group, an HP group, an antibody group and an inhibitor group, each of 6. HP was induced in all except the rats of the blank and Sham-HP groups by injecting carrageenan (Car) and prostaglandin E2 subcutaneously at the bottom of the left hind feet. The antibody and inhibitor groups were then given intrathecal injections of anti-ST2 antibody and a tumor necrosis factor α (TNF-α)-specific inhibitor, respectively. In the second experiment, 42 SD rats were randomly divided into a Sham-HP group, an HP group, a TENSⅠgroup, a TENS II group, a TENS I inhibitor group, a TENS II inhibitor group, and a Sham-TENS group, each of 6. All of the groups had HP induced as in experiment one. All of the rats except those in the Sham-HP, HP and Sham-TENS groups were then given TENS, and the TENS I and II inhibitor groups were offered intrathecal injection of TNF-α-specific inhibitors. Mechanical pain thresholds (MPTs) were documented 4h, 24h, 48h, 72h, 6d, 7d 4h, 7d 1h, and 7d after the Car injections. Western blotting was used to measure the protein expressions of IL-33, ST2 and TNF-α 6d after the Car injection in both experiments.Results:In experiment one, the average MPTs of the HP, antibody and inhibitor groups had decreased significantly 4 hours after the Car injection compared with the blank and Sham-HP groups. However, 7d 1h after the Car injection the value had increased significantly in the Sham-HP, antibody and inhibitor groups compared with the HP group, while the expressions of IL-33, ST2 and TNF-α had decreased significantly. In experiment two, by 4 hours after the Car injection, the average MPT of all the other groups had decreased significantly compared with the Sham-HP group. Moreover, by 7d 1h after the Car injection, the average MPTs of the groups receiving TENS had increased significantly, with significantly lower MPT in the TENS Ⅱ group than in group Ⅰ, on average. There was also significantly higher expression of IL-33, ST2 and TNF-α in group II. Compared with the TENS Ⅰ and Ⅱ groups, the average MPT was significantly higher in the TENS I and Ⅱ inhibitor groups, but IL-33, ST2 and TNF-α expression was lower.Conclusions:TENS can inhibit TNF-α expression, which influences the signals of the DRG IL-33/ST2 signaling pathway to reverse hyperalgesia. TENS combined with anti-TNF-α treatment is superior to TENS alone in treating hyperalgesia.

AIM:To describe the dynamic characteristics of mitochondria in the development of mouse embryonic hematopoietic stem cells,and to explore the function of mitochondria in this process.METHODS:Single-cell transcrip-tomic data of continuous developmental hematopoietic stem cell-related populations were analyzed to describe the dynamic changes of genes related to mitochondrial synthesis and energy metabolism.To explore the dynamic changes in the number and activity of mitochondria during the development of hematopoietic stem cells,we detected the mitochondrial number and mitochondrial membrane potential of the cells in each stage of hematopoietic stem cell development by fluorescent probe staining combined with flow cytometry.We added small molecule inhibitors of mitochondrial synthesis and energy metabolism and used hematopoietic cell colony formation assay to detect the effect of mitochondrial function inhibition on the induction of hematopoietic products in vitro.RESULTS:(1)Single-cell transcriptome analysis showed that genes in-volved in mitochondrial synthesis and oxidative phosphorylation were significantly up-regulated in endothelial cell and type Ⅰ pre-hematopoietic stem cell compared with those involved in glycolysis,and these genes could significantly distinguish continuous dynamic populations.(2)The results of fluorescence staining and flow cytometry analysis showed that mito-chondrial number and mitochondrial membrane potential had an increasing trend during the continuous development of he-matopoietic stem cell,reaching the highest level in the precursor stage of type 2 pre-hematopoietic stem cell,and decreasing in the mature hematopoietic stem cell of fetal liver.(3)Compared with control group,inhibition of mitochondrial respirato-ry chain Ⅰ and Ⅴ significantly reduced the number of hematopoietic colonies(P<0.05).CONCLUSION:(1)Genes re-lated to mitochondrial synthesis and oxidative phosphorylation are highly expressed in hemogenic endothelial cells and type Ⅰpre-hematopoietic stem cells,and can be used to distinguish continuous developing populations.(2)The mitochondrial number and mitochondrial membrane potential increased continuously during hematopoietic stem cell development and reached the highest level in type 2 pre-hematopoietic stem cells.(3)Inhibition of mitochondrial respiratory chain Ⅰ and Ⅴ significantly reduced the production of hematopoietic products in vitro.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.