Assessing the causal association between sleep apnea and the human gut microbiome composition: A two-sample Mendelian randomization study.

Background: Studies have linked gut microbiota dysbiosis with sleep apnea; however, no causal relationship was found in human subjects. Finding new targets for the pathophysiology of sleep apnea might be made possible by systematically investigating the causal relationship between the human gut microbiota and sleep apnea. Methods: A two-sample Mendelian randomization analysis was conducted. The human gut microbiome composition data, spanning five taxonomic levels, were acquired from a genome-wide association study that included 18,340 participants from 24 cohorts. Genome-wide association study data for sleep apnea were obtained from the Sleep Disorder Knowledge Portal for primary analysis and the FinnGen consortium for meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results: Using inverse-variance weighted analysis, eight microbial taxa were initially found to be substantially linked with the apnea-hypopnea index. Only three microbial taxa remained significant associations with sleep apnea when combined with the FinnGen consortium (the class Bacilli: B = 8.21%, 95% CI = 0.93%-15.49%; p = 0.03; the order Lactobacillales: B = 7.55%, 95% CI = 0.25%-4.85%; p = 0.04; the genus RuminococcaceaeUCG009: B = -21.63%, 95% CI = -41.47% to -1.80%; p = 0.03). Conclusions: Sleep apnea may lead to gut dysbiosis as significant reductions in butyrate-producing bacteria and increases in lactate-producing bacteria. By integrating genomes and metabolism, the evidence that three microbiome species are causally linked to sleep apnea may offer a fresh perspective on the underlying mechanisms of the condition.

Clinical features of non-syndromic late developing supernumerary teeth: a sign of the third dentition?

OBJECTIVES: This study aimed to summarize the clinical features of non-syndromic late developing supernumerary teeth (LDST) and comparisons with common supernumerary teeth (ST) and explore the association between LDST and the third dentition. MATERIALS AND METHODS: This study retrospected cone-beam computed tomography (CBCT) and medical history of 41,903 consecutive patients from January to December 2021. Comparisons between ST and LDST were evaluated by Chi-square test or Fisher exact test. Correlation between chronological age and dental stage age was evaluated by Spearman's rank correlation coefficient. Binary logistic regression analysis was used to explore the features of LDST originating from the third dentition. RESULTS: Sixty patients with 126 non-syndromic LDST and 1602 patients with 1988 non-syndromic ST were identified. The prevalence of ST and LDST was 3.82% and 0.14%, respectively, with a male-female ratio of 1.78:1 and 1.31:1. LDST patients mainly had LDST in multiple (58.33%) and bilaterally (41.67%), with an average of 2.1/patient. Most LDST were normal-shaped (84.13%), vertically oriented (71.43%), located in the mandible (80.16%), and distributed in the premolar region (82.54%). The study also indicated that the development of LDST was correlated with permanent teeth, with LDST developing 6.48 to 10.45 years later. In this study, 72.22% of LDST met the clinical criteria for the third dentition. CONCLUSIONS: LDST manifested different clinical features from common ST. LDST might be closely related to the third dentition. CLINICAL RELEVANCE: This work would help to comprehend LDST from a clinical perspective, and may be complementary to the criteria of the third dentition.

Impact of rise and fall phases of shear on platelet activation and aggregation using microfluidics.

Blood flow disorders are often the result of the non-physiological narrowing of blood arteries caused by atherosclerosis and thrombus. The blood then proceeds through rising-peak-decreasing phases as it passes through the narrow area. Although abnormally high shear is known to activate platelets, the shear process that platelets undergo in small arteries is complex. Thus, understanding how each shear phase affects platelet activation can be used to improve antiplatelet therapy and decrease the risk of side effects like bleeding. Blood samples were sheared (68.8 ms,5200 s-1) in vitro by the microfluidic technique, and platelet activation levels (P-selectin and integrin αIIbß3) and von Willebrand factor (vWF) binding to platelets were analyzed by flow cytometry. Post-stenosis platelet aggregation was dynamically detected using microfluidic technology. We studied TXA2, P2Y12-ADP, and integrin αIIbß3-fibrinogen receptor pathways by adding antiplatelet drugs, such as acetylsalicylic acid (ASA, an active ingredient of aspirin that inhibits platelet metabolism), ticagrelor (hinders platelet activation), and tirofiban (blocks integrin αIIbß3 receptor) in vitro, respectively, to determine platelet activation function mediated by transient non-physiological high shear rates. We demonstrated that platelets can be activated under transient pathological high shear rates. The shear rise and fall phases influenced shear-induced platelet activation by regulating the binding of vWF to platelets. The degree of platelet activation and aggregation increased with multiple shear rise and fall phases. ASA did not inhibit shear-mediated platelet activation, but ticagrelor and tirofiban effectively inhibited shear-mediated platelet activation. Our data demonstrated that the shear rise and fall phases play an important role in shear-mediated platelet activation and promote platelet activation and aggregation in a vWF-dependent manner. Blocking integrin αIIbß3 receptor and hindering P2Y12-ADP were beneficial to reducing shear-mediated platelet activation.

The Influences of Adverse Childhood Experiences and Social Support on Male Teenagers' Gaming Motivation: A Moderated Network Analysis.

INTRODUCTION: Strong gaming motivations can lead to gaming-related health problems, but how gaming motivations are formed is unclear. Therefore, we examined the impact of early life experiences on gaming motivations. METHODS: Questionnaire data on the gaming motivations, adverse childhood experiences, and social support of 2,171 teenaged online game players were modeled using moderated network analysis. RESULTS: All adverse childhood experience components positively correlated with achievement and escapism motivations (weight range: 0.08-0.40). Social support from friends (weight = -0.04) negatively moderated the relationship between achievement motivation and other adverse childhood experiences and positively moderated (weight = 0.01) the relationship between escapism motivation and familial dysfunction. DISCUSSION: The findings indicate that adverse childhood experiences foster negative gaming motivations. Additionally, social support moderates the relationship between adverse childhood experiences and gaming motivations. These findings offer valuable insights that nursing practitioners can apply to gaming-related health problem interventions and prevention in teenagers.

Relationship Between Sleep Duration and Cognitive Function in Older Adults: Analysis of NHANES and UK Biobank GWAS Data.

OBJECTIVES: To explore the relationship between sleep duration and cognitive functions in older adults using NHANES, a national US population study dataset, and to explore the causal association with Mendelian randomization (MR) using the UK Biobank. METHODS: First, an observational study was conducted with the NHANES database with participants ≥60 years. Sleep duration was measured with accelerometers for 7 consecutive days. Participants were divided into habitual short sleep (<7 h) and long sleep (>9 h) groups. Cognitive functions were measured with the CERAD Word Learning sub-set, Animal Fluency, and Digit Symbol Substitution test (DSST). Multivariate regression models were used to explore relationships between sleep duration and cognitive functions. Second, bidirectional MR was conducted with data for self-reported sleep duration, which came from a genome-wide association study (GWAS) comprising 446,118 adults from the UK Biobank, and general cognitive performance, which was obtained from a recent GWAS study (N = 257,841). Inverse-variance weighted (IVW) was used as the primary estimation of the outcome. RESULTS: In the observational study, 2687 participants were included. Sleep duration was associated with cognitive functions in a non-linear way. Habitual long sleep (>9°h) was associated with lower scores on DSST (OR = 0.01, p = .003) in the fully-adjusted model. The association between habitual short sleep and cognitive functions was insignificant. For the MR, genetically predicted lower general cognitive performance was causally associated with a higher prevalence of habitual short sleep (OR = 0.97, p = 5.1 × 10-7) and long sleep (OR = 0.97, p = 8.87 × 10-16). DISCUSSION: Short and long sleep duration might be both causally associated with worse outcomes of cognitive functions in older adults, highlighting the importance of maintaining sleep health.

Antiplatelet Agents Inhibit Platelet Adhesion and Aggregation on Glass Surface Under Physiological Flow Conditions: Toward a Microfluidic Platelet Functional Assay Without Additional Adhesion Protein Modification.

ABSTRACT: As the pathogenesis of arterial thrombosis often includes platelet adhesion and aggregation, antiplatelet agents are commonly used to prevent thromboembolic events. Here, a new microfluidic method without additional adhesion protein modification was developed to quantify the inhibitory effect of antiplatelet drugs on the adhesion and aggregation behavior of platelets on glass surfaces under physiological flow conditions. Polydimethylsiloxane-glass microfluidic chips were fabricated by soft photolithography. Blood samples from healthy volunteers or patients before and after taking antiplatelet drugs flowed through the microchannels at wall shear rates of 300 and 1500 second -1 , respectively. The time to reach 2.5% platelet aggregation surface coverage (Ti), surface coverage (A 150s ), and mean fluorescence intensity (F 150s ) were used as quantitative indicators. Aspirin (80 µM) prolonged Ti and reduced F 150s . Alprostadil, ticagrelor, eptifibatide, and tirofiban prolonged Ti and reduced A 150s and F 150s in a concentration-dependent manner, whereas high concentrations of alprostadil did not completely inhibit platelet aggregation. Aspirin combined with ticagrelor synergistically inhibited platelet adhesion and aggregation; GPIb-IX-von Willebrand factor inhibitors partially inhibited platelet aggregation, and the inhibition was more pronounced at 1500 than at 300 second -1 . Patient administration of aspirin or (and) clopidogrel inhibited platelet adhesion and aggregation on the glass surface under flow conditions. This technology is capable of distinguishing the pharmacological effects of various antiplatelet drugs on inhibition of platelet adhesion aggregation on glass surface under physiological flow conditions, which providing a new way to develop microfluidic platelet function detection method without additional adhesive protein modification for determining the inhibitory effects of antiplatelet drugs in the clinical setting.

Evaluating the impact of transient shear stress on platelet activation, adhesion, and aggregation with microfluidic chip technique.

BACKGROUND: When nonphysiological stenosis occurs, the transient high shear stress formed in vessels increases the risk of thrombosis and is a potential factor for cardiovascular diseases. But the platelet adhesion and aggregation behavior at nonphysiological post-stenosis and its affecting factors are not fully understood yet. METHODS: In this experiment, platelet aggregation on collagen and fibrinogen at different shear stresses and different hematocrits were observed by microfluidic technology. Platelet activation (P-selectin, glycoprotein IIb/IIIa) and monocyte-platelet aggregate (MPA) levels under different shear stresses were analyzed by flow cytometry. RESULTS: On fibrinogen, platelets aggregate more at higher shear stress conditions. While on collagen, it becomes more difficult for platelets to form stable aggregation at higher shear stress conditions. If platelets adhere initially at low shear stress, stable platelet aggregation can be formed at subsequent high shear stress. Moreover, when the shear stress increases, platelet activity markers (P-selectin, glycoprotein IIb/IIIa and MPAs) increase significantly. Hematocrit affects the degree of platelet aggregation, and the influence of hematocrit is obvious at high shear stress. CONCLUSION: Transient high shear stress (46 ms) can effectively activate platelets. Platelet aggregation behavior was different for coated fibrinogen and collagen protein. Stable platelet adhesion at post-stenosis is more dependent on fibrinogen and platelet aggregation is stable on both fibrinogen and collagen. Hematocrit can significantly affect the formation of platelet aggregation.

Profiles of fear of missing out and their social media use among young adults: A six-month longitudinal study.

This longitudinal study used a person-centered approach to differentiate fear of missing out (FoMO) among subgroups of individuals using latent profile analysis (LPA). The subgroups were identified according to trait-FoMO (a specific predisposition) and state-FoMO (a specific cognition in the online context) items. Data were collected from 1125 participants (70.04 % female, age range 17-26 years, Mage = 20.52 years). The LPA showed five distinct profiles: highest FoMO, high trait-FoMO high state-FoMO, high trait-FoMO low state-FoMO, low trait-FoMO high state-FoMO, and low trait-FoMO low state-FoMO. We further explored how these profiles relate to social media use. The results revealed significant differences between profiles in terms of social media engagement, social media self-control failure, and problematic social media use and could be used to predict social media use behaviors of 437 participants (77.35 % female, age range 18-27 years, Mage = 20.60 years) six months later. Thus, the combination of high trait-FoMO and high state-FoMO may mean more frequent social media engagement and could be an important risk factor for social media self-control failure and problematic social media use. Additionally, state-FoMO should be considered in prevention and intervention strategies aimed at addressing young adults' problematic social media use.

The rapid change of shear rate gradient is beneficial to platelet activation.

Fluid shear plays a key role in hemostasis and thrombosis, and the purpose of this study was to investigate the effect of shear gradient change rate (SGCR) on platelet reactivity and von Willebrand factor (vWF) activity and its mechanism. In this study, we developed a set of microfluidic chips capable of generating different shear gradients and simulated the shear rate distribution in the flow field by COMSOL Multiphysics software. Molecular markers of platelet activation (P-selectin, activated GPIIb/IIIa, phosphatidylserine exposure, and monocyte-platelet aggregate formation) were analyzed by flow cytometry. Platelet aggregation induced by shear gradient was studied by a microfluidic experimental platform, and plasma vWF ristocetin cofactor (vWF: RCO) activity was investigated by flow cytometry. The expression of p-Akt was studied by Western blotting. The results showed that the faster the SGCR, the higher the expression of platelet p-Akt, and the stronger the platelet reactivity and vWF activity. This indicates that fluid shear stress can activate platelets and vWF in a shear gradient-dependent manner through the PI3K/AKT signal pathway, and the faster the SGCR, the more significant the activation effect.

What is the context? Recent studies have shown that fluid shear stress plays a key role in platelet activation and thrombosis. However, its mechanism and effect have not been fully elucidated.The development of microfluidic chip technology enables people to study platelet function in a precisely controlled flow field environment.Previous studies have shown that the PI3K-AKT signal pathway may be a mechanically sensitive signal transduction pathway.What is new?In this study, we designed a microfluidic model with different narrow geometry, and controlled the injection pump to perfuse fluid at the same flow rate, so that the platelets flowing through the model experienced the flow field environment of different shear gradients.We studied the activities of platelets and von Willebrand factor in different flow fields and explored their signal transduction pathways.What is the impact? Our results suggest that vascular stenosis does increase platelet activity and the risk of thrombosis. However, its ability to activate platelets is not only related to the peak shear rate and shear time, but also closely related to the decreasing rate of shear gradient. Even if the peak shear rate at the stenosis is the same, the faster the shear rate decreases, the higher the reactivity of platelets and von Willebrand factor, which may be mediated by the PI3K-AKT signal pathway. This study not only helps clinicians to judge the risk of thrombosis in patients with atherosclerosis or percutaneous coronary intervention, but also helps us to better understand the mechanism of shear-induced platelet activation.

Comparisons are Odious? The neural basis of in-group and out-group social comparison among game players: An fMRI study.

Social comparison is an important way for individuals to define their social characteristics. Online games with a large amount of social information provide a convenient platform for social comparison between players. However, few studies have examined the neural basis of different social comparisons in game players. This study aims to explore the activation of brain regions triggered by social comparison in different contexts and the possible moderating effect of group identity. A total of 26 subjects participated in our experiment. We referred to the minimum group paradigm to evoke group identity and used the dot estimation paradigm to generate in-group or out-group social comparisons. The activation of brain regions was measured and analyzed. Compared to upward comparison, the fusiform gyrus, putamen, lentiform nucleus, precuneus, and precentral gyrus were significantly activated in downward comparison when the group identity of the comparison object was the same as that of the player. When the two had different identities, downward comparison significantly activated the angular gyrus, middle frontal gyrus, and superior frontal gyrus. However, the moderating effect of group identity was not significant. Further functional connectivity analysis based on the brain region activation results was performed. Our study has shown that social comparison in group contexts leads to the activation of different brain regions and provides neurophysiological evidence of social interaction among game players.

Self-reported sleep status and influencing factors: a web-based national cross-sectional survey in China.

OBJECTIVES: To investigate self-reported sleep duration, sleep timing, sleep status and influencing factors in the Chinese population. METHODS: This web-based cross-sectional survey was conducted in 2022, covering 31 provinces (91%) in China. 11,000 questionnaires were collected, of which 8970 were valid for analysis. Self-reported sleep habits, problems and quality were investigated. Good or fair sleep ratings, enough duration, regular, with no sleep disturbances and <30 min sleep latency was defined as a composite variable: 'Good sleep'. Factors influencing sleep patterns and 'Good sleep' were analyzed by multivariate logistic regression. RESULTS: Most participants sleep less than 7 h per night (55.13%), usually go to bed at 10-12 pm (47.99%), wake up at 6-8 am (49.86%), and take less than 30 min to fall asleep (66.30%) with regular sleep schedule (76.01%). Only 12.36% have 'Good sleep'. In the past 3 months, 46.80% of the participants reported symptoms of insomnia, and 21.54% had snoring problems. Among the adults, the young, males, college students, freelancers, and those who resided in urban areas and pandemic-free areas slept later, and the northerners woke up earlier. The adults with low-moderate and moderate income and the minors at elementary and middle school slept earlier and woke up earlier. Mid-aged adults who often napped at noon were more likely to have 'Good sleep' than any other age group, and urban dwellers with the same habit were more likely to have 'Good sleep' than people dwelled in other regions. While people who slept late, woke up too early or too late, slept too little or too much, resided at GMT 7-8 area or pandemic area, had high income, or took up some occupations (entrepreneurs/individuals, professionals, manual and non-manual workers, housewives) were less likely to get a 'Good sleep'. CONCLUSIONS: The national survey provided a sleep profile of the Chinese population. Both socio-economic status and personal sleep hygiene habits had an impact on 'Good sleep'.

Long-term efficacy of mandibular advancement devices in the treatment of adult obstructive sleep apnea: A systematic review and meta-analysis.

This study aims to review the long-term subjective and objective efficacy of mandibular advancement devices (MAD) in the treatment of adult obstructive sleep apnea (OSA). Electronic databases such as PubMed, Embase, and Cochrane Library were searched. Randomized controlled trials (RCTs) and non-randomized self-controlled trials with a treatment duration of at least 1 year with MAD were included. The quality assessment and data extraction of the included studies were conducted in the meta-analysis. A total of 22 studies were included in this study, of which 20 (546 patients) were included in the meta-analysis. All the studies had some shortcomings, such as small sample sizes, unbalanced sex, and high dropout rates. The results suggested that long-term treatment of MAD can significantly reduce the Epworth sleepiness scale (ESS) by -3.99 (95%CI -5.93 to -2.04, p<0.0001, I2 = 84%), and the apnea-hypopnea index (AHI) -16.77 (95%CI -20.80 to -12.74) events/h (p<0.00001, I2 = 97%). The efficacy remained statistically different in the severity (AHI<30 or >30 events/h) and treatment duration (duration <5y or >5y) subgroups. Long-term use of MAD could also significantly decrease blood pressure and improve the score of functional outcomes of sleep questionnaire (FOSQ). Moderate evidence suggested that the subjective and objective effect of MAD on adult OSA has long-term stability. Limited evidence suggests long-term use of MAD might improve comorbidities and healthcare. In clinical practice, regular follow-up is recommended.

Porphyrin-anthracene covalent organic frameworks for sustainable photosterilization.

Covalent organic frameworks (COFs) have promising applications in enhanced phototherapy. However, COFs that can sustainably play a role in phototherapy without continuous irradiation are extremely scarce. Herein, we report the fabrication of porphyrin-anthracene multifunctional COFs (Por-DPA) for sustainable photosterilization and bacterial-infected wound healing. A porphyrin photosensitizer, as one of the monomers, was used to provide photothermal and photodynamic activities under irradiation. An anthracene derivative, a good chemical source of singlet oxygen (1O2), was selected as another monomer to capture 1O2 and release it continuously via cycloreversion in the dark. The prepared Por-DPA COF prevents the self-aggregation quenching of the photosensitizer and thermal damage caused by continuous exposure to external light sources. Besides, Por-DPA exhibits good photothermal conversion performance and efficient 1O2 production capacity through dual pathways of photosensitization and cycloreversion. The developed sustainable photosterilization platform not only has good bactericidal effects on Escherichia coli and Staphylococcus aureus, but also promotes wound healing without obvious side effects, and is expected to be a novel efficient bactericide.

Orthodontic appliances for the treatment of pediatric obstructive sleep apnea: A systematic review and network meta-analysis.

This systematic review and network meta-analysis aims to preliminarily investigate the efficacy of different orthodontic appliances for the treatment of pediatric obstructive sleep apnea (OSA). Electronic databases were systematically searched. Randomized and non-randomized controlled trials with patients <18 y treated with either mandibular advancement appliance (MAA), rapid maxillary expansion (RME), or myofunctional therapy (MFT) were included. A network meta-analysis using multivariate random effects was conducted to estimate pooled differences using the apnea-hypopnea index (AHI) as the main outcome. Eleven studies (595 patients) were included in the analysis. Compared with control, MAA was associated with significant reductions in AHI of -2.18/h (95%CI -3.48 to -0.89, p = 0.001). Combined treatment of RME + adenotonsillectomy (AT) and RME + MAA showed a significant decrease in AHI, with -5.13/h (95%CI -7.50 to -2.76, p < 0.0001) and -3.79 (95%CI -5.21 to -2.37, p < 0.0001), respectively. MFT was associated with a -2.45/h (95%CI -4.76 to -0.14, p = 0.038) decrease in AHI. However, RME alone was not associated with significant AHI reduction (0.02, 95%CI -1.72 to 1.75, p = 0.985). The heterogeneity of the network meta-analysis was I2 = 32.6%. Limited evidence indicated that MAA (alone or combined with RME) and RME + AT were associated with benefits for pediatric patients with OSA. This study could not find convincing evidence of a significant benefit of other orthodontic appliances over control.

Magnetic resonance imaging features of bile duct adenoma.

Objectives: To evaluate the magnetic resonance imaging (MRI) features of bile duct adenoma. Methods: The data of 28 patients [with 32 pathologically confirmed bile duct adenomas, including 15 with malignant change (malignant group) and 17 without malignant change (benign adenoma group)] were retrospectively reviewed. Abdominal MRI was performed for all patients; in addition, dynamic enhanced MRI was performed for 18 lesions. The MRI features, including lesion location, maximum size, morphology, signal characteristics, enhancement type, and appearance of the bile duct, were assessed by two abdominal radiologists. Apparent diffusion coefficient (ADC) values were measured and compared. Results: Of the 32 bile duct adenomas, 22 (68.75%) involved the common bile duct (CBD). While 14/32 (43.75%) lesions presented as focal eccentric-type masses, 9/32 (28.13%) presented as plaque-like masses, 4/32 (12.50%) as bile duct casting masses, and 5/32 (15.62%) as infiltrative masses. A frond-like superficial appearance was seen in 8/32 (25%) lesions. Infiltrative masses were significantly more common in the malignant group than in the benign adenoma group (P = 0.015). While 23/32 (71.88%) lesions were isointense on T1-weighted imaging (T1WI), 24/32 (75%) were hyperintense on T2-weighted imaging (T2WI). Bile duct dilatation was present upstream of the lesion in all cases. Bile duct dilatation at the lesion was seen in 24/32 (75%) cases and downstream of the lesion in 6/32 (18.75%) cases. Of the 18 lesions that underwent dynamic enhanced MRI, 14 (77.78%) showed moderate enhancement and 13 (72.22%) showed persistent enhancement. On diffusion-weighted imaging (DWI), 27/32 (84.37%) lesions showed hyperintensity. Mean ADC value was comparable between the malignant group and the benign adenoma group (P = 0.156). Conclusions: Bile duct adenoma primarily presents as intraductal growth in the CBD, usually with bile duct dilatation at the lesion site or upstream to it. Most lesions are isointense on T1WI, are hyperintense on T2WI and DWI, and show moderate enhancement. A superficial frond-like appearance of the lesion and bile duct dilatation at the lesion or downstream to it might be characteristics of bile duct adenoma. An infiltrative appearance might indicate malignant transformation.

Phenotypic characteristics of taurodontism and a novel WNT10A variant in non-syndromic oligodontia family.

OBJECTIVE: Variants in wingless-type MMTV integration site family member 10A (WNT10A) have been proposed to be the most common cause of non-syndromic oligodontia (NSO). The goal of the present study was to identify the novel WNT10A variants in Chinese families with NSO. DESIGN: Clinical data were collected from 39 families with oligodontia admitted to the Hospital of Stomatology Hebei Medical University (China) from 2016 to 2022. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify WNT10A variants in three families with non-syndromic oligodontia. Amino acid conservation analysis and protein conformational analysis were conducted for the WNT10A variant. Genotype-phenotype analysis was performed on the previously reported WNT10A variants related to NSO. RESULTS: We found a novel heterozygous WNT10A variant c.1127 G>A (p.Cys376Tyr) and two reported heterozygous variants c.460 C>A (p.Leu154Met) and c.511 C>T (p.Arg171Cys). Structural modeling showed that the novel WNT10A variant was located in a highly conserved domain, which led to structural damage of WNT10A protein. In addition, we found that the phenotype of the WNT10A variants affected the maxillary second premolars, followed by the mandibular second premolars, and rarely affected the maxillary central incisor. Herein, it is the first time to report that NSO patients with WNT10A monoallele mutation carry taurodontism phenotype and 6.1% prevalence of taurodontism in WNT10A-related NSO patients. CONCLUSIONS: Our results demonstrated that the novel variant c.1127 G>A (p.Cys376Tyr) of WNT10A causes NSO. The present study expanded the known variation spectrum of WNT10A and provided valuable information for genetic counseling of families.

[Microfluidic Chip and Flow Cytometry for Examination of the Antiplatelet Effect of Ticagrelor].

Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 µmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.