Surgical Management of Airway Obstruction Following Posterior Pharyngeal Flap.

BACKGROUND: Posterior pharyngeal flap (PPF) is effective in managing velopharyngeal insufficiency (VPI) but is of airway obstruction risk. This study compared the effectiveness and complications of two PPF revision procedures and screened potential prognostic factors to postoperative hypernasality and persistent obstruction. METHODS: Patients who received flap division (FD) or port enlargement (PE) for airway obstruction following PPF were reviewed. Ventilation status was assessed using the nasal obstruction symptom evaluation (NOSE) scale, and velopharyngeal closure was assessed using subjective speech evaluation and nasopharyngoscopy. The effectiveness of ventilation relief and complication rate (hypernasality and persistent obstruction) of the two techniques were compared. A comprehensive panel of factors, including age, velopharyngeal mobility, obstruction laterality, body mass index, jaw relationship, and adenoid hypertrophy, were evaluated for correlation with complications. RESULTS: 79 patients were enrolled, with 51 receiving FD and 28 PE. Both techniques significantly improved ventilation dysfunction and hyponasality. Mild hypernasality occurred among 10 cases in the FD group and 3 in the PE group. Age at surgery was significantly associated with persistent obstruction after PPF revision. The occurrence of persistent obstruction was significantly higher among patients below 12 years than those above. Obstruction laterality was suggested in significant correlation with hypernasality post-PPF revision. Among patients with unilateral port obstruction, the occurrence of hypernasality after FD was significantly higher than after PE. CONCLUSION: Both flap division and port enlargement are effective revision procedures to relieve airway obstruction after PPF. Patients below 12 years are more likely to experience persistent ventilation problem after PPF revision.

Lithium chloride promotes mesenchymal-epithelial transition in murine cutaneous wound healing via inhibiting CXCL9 and IGF2.

Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re-epithelialization through mesenchymal-epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal-epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal-derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal-epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal-epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal-epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by ß-catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re-epithelialization in future.

Evaluation of Secondary Alveolar Bone Grafting for Unilateral Complete Cleft Alveolus: A Retrospective Cone Beam Computed Tomography-Based Study.

Background: In patients with cleft lip and palate (CLP), secondary alveolar bone grafting (SABG) with particulate cancellous bone marrow (PCBM) is recommended. Objective: To compare bone graft outcomes in patients with unilateral CLP, when SABG is completed before or after canine tooth eruption (ACE or BCE), as measured by cone beam computed tomography (CBCT). Methods: Patients were allocated into two cohorts, ACE and BCE. The outcomes were evaluated using CBCT, followed by univariate and multifactorial analyses. Results: A total of 468 patients (age 11.61 ± 4.03 years; male/female 288/180) were analyzed, including 282 in the BCE group (9.41 ± 1.59 years, 175/107) and 186 in the ACE group (14.95 ± 4.31 years, 113/73). Although 5-level assessment revealed no significant difference in clinical success rate (>4 points) between the BCE and ACE groups (53.90% vs. 47.85%, p = 0.20), BCE group showed significantly higher rate of bone bridges formation (73.05% vs. 62.90%, p = 0.02), which can be attributed to variations in orthodontic participation and follow-up time. Independent predictors of graft failure were wide cleft, severe oronasal fistula, no palatal bone wall, and insufficient PCBM filling (p < 0.01). Conclusions: SABG should be performed before canine eruption with more aggressive PCBM filling and oral fistula management.

Acupuncture and related acupoint therapies for smoking cessation: An umbrella review and updated meta-analysis.

INTRODUCTION: Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. METHODS: Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. RESULTS: Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02-2.02; I2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74-1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14-1.87; I2=5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. CONCLUSIONS: Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

Integrative Salt Selection and Formulation Optimization: Perspectives of Disproportionation and Microenvironmental pH Modulation.

We report a novel utilization of a pH modifier as a disproportionation retardant in a tablet formulation. The drug molecule of interest has significant bioavailability challenges that require solubility enhancement. In addition to limited salt/cocrystal options, disproportionation of the potential salt(s) was identified as a substantial risk. Using a combination of Raman spectroscopy with chemometrics and quantitative X-ray diffraction in specially designed stress testing, we investigated the disproportionation phenomena. The learnings and insight drawn from crystallography drove the selection of the maleate form as the target API. Inspired by the fumarate form's unique stability and solubility characteristics, we used fumaric acid as the microenvironmental pH modulator. Proof-of-concept experiments with high-risk (HCl) and moderate-risk (maleate) scenarios confirmed the synergistic advantage of fumaric acid, which interacts with the freebase released by disproportionation to form a more soluble species. The resultant hemifumarate helps maintain the solubility at an elevated level. This work demonstrates an innovative technique to mediate the solubility drop during the "parachute" phase of drug absorption using compendial excipients, and this approach can potentially serve as an effective risk-mitigating strategy for salt disproportionation.

Embosphere microspheres size for bronchial artery embolization in patients with hemoptysis caused by bronchiectasis: a retrospective comparative analysis of 500-750 versus 700-900 µm microspheres.

BACKGROUND: Bronchial arterial embolization (BAE) has been accepted as an effective treatment for bronchiectasis-related hemoptysis. However, rare clinical trials compare different sizes of specific embolic agents. This study aims to evaluate whether different Embosphere microsphere sizes change the outcome of BAE. METHODS: A retrospective review was conducted on consecutive patients with bronchiectatic hemoptysis who were scheduled to undergo BAE treatment during a period from January 2018 to December 2022. The patients received BAE using microspheres of different sizes: group A patients were treated with 500-750 µm microspheres, and group B patients were treated with 700-900 µm microspheres. The cost of embolic microspheres (Chinese Yuan, CNY), duration of hospitalization, complications, and hemoptysis-free survival were compared between patients in group A and those in group B. A Cox proportional hazards regression model was used to identify predictors of recurrent hemoptysis. RESULTS: Median follow-up was 30.2 months (range, 20.3-56.5 months). The final analysis included a total of 112 patients (49-77 years of age; 45 men). The patients were divided into two groups: group A (N = 68), which received 500-750 µm Embosphere microspheres, and group B (N = 44), which received 700-900 µm Embosphere microspheres. Except for the cost of embolic microspheres(group A,5314.8 + 1301.5 CNY; group B, 3644.5 + 1192.3 CNY; p = 0.042), there were no statistically significant differences in duration of hospitalization (group A,7.2 + 1.4 days; group B, 8 + 2.4days; p = 0.550), hemoptysis-free survival (group A, 1-year, 2-year, 3-year, 85.9%, 75.8%, 62.9%; group B, 1-year, 2-year, 3-year, 88.4%, 81.2%,59.4%;P = 0.060), and complications(group A,26.5%; group B, 38.6%; p = 0.175) between the two groups. No major complications were observed. The multivariate analysis results revealed that the presence of cystic bronchiectasis (OR 1.61, 95% CI 1.12-2.83; P = 0.001) and systemic arterial-pulmonary shunts (SPSs) (OR 1.52, 95% CI 1.10-2.72; P = 0.028) were independent risk factors for recurrent bleeding. CONCLUSIONS: For the treatment of BAE in patients with bronchiectasis-related hemoptysis, 500-750 µm diameter Embosphere microspheres have a similar efficacy and safety profile compared to 700-900 µm diameter Embosphere microspheres, especially for those without SPSs or cystic bronchiectasis. Furthermore, the utilization of large-sized (700-900 µm) Embosphere microspheres is associated with the reduced cost of an embolic agent.

[Clinical Characteristics Analysis of 1051 Cases of Cleft Lip With/Without Cleft Palate in the Ethnic Tibetan Population]. / 1051ä¾‹è—æ—å”‡è ­è£‚æ‚£è€ ä¸´åºŠç‰¹å¾åˆ†æž.

Objective: To examine the characteristics of the prevalence of congenital cleft lip with/without cleft palate in the ethnic Tibetan population and to provide support for the precise prevention and treatment of cleft lip with/without cleft palate in the Tibetan population. Methods: The clinical data of Tibetan patients with cleft lip with/without cleft palate were collected and the clinical characteristics of the patients were analyzed. The patients' age ranged from 2 months to 51 years old. All the subjects were admitted to West China Stomatology Hospital, Sichuan University for the treatment of cleft lip with/without cleft palate between January 2016 and August 2023. Most of the subjects came from Sichuan Province and the Tibet Autonomous Region. Results: A total of 1051 patients were enrolled and children aged under 12 months (460 cases) accounted for the largest proportion. Among the subjects, 383 had cleft lip only (36.44%), 140 had cleft palate only (13.32%), and 528 had cleft lip with cleft palate (50.24%). The male-to-female ratios of patients with cleft lip only (0.99∶1), cleft palate only (0.54∶1), and cleft lip with cleft palate (1.67∶1) exhibited significant differences (P<0.001). However, there was no significant difference in the male-to-female ratio in patients with cleft lip only or those with cleft lip with cleft palate when the subjects were divided into two groups according to whether they had unilateral or bilateral cleft lip with/without cleft palate. Most of the patients with bilateral cleft lip were female, while most of the patients with unilateral cleft lip and unilateral or bilateral cleft lip with cleft palate were male. The unilateral cleft lip with/without cleft palate was located predominantly on the left side. Syndromic cleft lip with/without cleft palate accounted for 3.43% of all the cases and the most common concomitant deformity was congenital heart disease. 3.81% (40 cases) of the patients had a family history. In the patients with cleft lip only and those with cleft palate only, the proportion of patients having parents with corresponding phenotypes was higher than those of other phenotypes of cleft lip with/without cleft palate. Regarding the birth time distribution of the children with cleft lip with/without cleft palate, Spring saw the highest number of births of these children (311 cases, 29.59%), while Winter saw the lowest number of births (231 cases, 21.98%). Conclusion: The cases of cleft lip with/without cleft palate in the ethnic Tibetan population are predominantly cleft lip and palate. Unilateral cleft lip only or cleft lip with palate is predominantly located on the left side. Lip disease phenotypes may be more heritable.

Examining the relationship between self-efficacy, career development, and subjective wellbeing in physical education students.

We investigated the relationship between self-efficacy and career development via subjective well-being of students majoring in physical education. Life satisfaction, positive affect, and negative affect were the componennts of subjective well-being. Participants were the 1381 adolescents with major in physical education with an age range of 18-22 years (Mage = 19.5 ± 1; females = 34.76%). Hayes PROCESS model was used to develop a multiple mediation model. The results suggest that higher self-efficacy leads to better career development. Further, a significant mediating role was played by negative and positive affect in case of the relationship between self-efficacy and career exploration, but life-satisfaction is not significant mediator. Conversely, life satisfaction and positive affect are significant mediators between self-efficacy and career adaptability but negative affect is not. The findings suggest that self-efficacy and subjective well-being benefit career development of adolescents in the physical education field.

The reciprocity of skeletal muscle and bone: an evolving view from mechanical coupling, secretory crosstalk to stem cell exchange.

Introduction: Muscle and bone constitute the two main parts of the musculoskeletal system and generate an intricately coordinated motion system. The crosstalk between muscle and bone has been under investigation, leading to revolutionary perspectives in recent years. Method and results: In this review, the evolving concept of muscle-bone interaction from mechanical coupling, secretory crosstalk to stem cell exchange was explained in sequence. The theory of mechanical coupling stems from the observation that the development and maintenance of bone mass are largely dependent on muscle-derived mechanical loads, which was later proved by Wolff's law, Utah paradigm and Mechanostat hypothesis. Then bone and muscle are gradually recognized as endocrine organs, which can secrete various cytokines to modulate the tissue homeostasis and remodeling to each other. The latest view presented muscle-bone interaction in a more direct way: the resident mesenchymal stromal cell in the skeletal muscle, i.e., fibro-adipogenic progenitors (FAPs), could migrate to the bone injury site and contribute to bone regeneration. Emerging evidence even reveals the ectopic source of FAPs from tissue outside the musculoskeletal system, highlighting its dynamic property. Conclusion: FAPs have been established as the critical cell connecting muscle and bone, which provides a new modality to study inter-tissue communication. A comprehensive and integrated perspective of muscle and bone will facilitate in-depth research in the musculoskeletal system and promote novel therapeutic avenues in treating musculoskeletal disorders.

Review on the Role of IRF6 in the Pathogenesis of Non-syndromic Orofacial Clefts.

Non-syndromic orofacial clefts (NSOCs) are the most common craniofacial malformation. In the complex aetiology and pathogenesis of NSOCs, genetic factors play a crucial role and IRF6, located at chromosome 1q32.2, is the best documented NSOC susceptibility gene. IRF6 is a key factor in oral maxillofacial development and known to contribute the most in NSOCs. It is essential to conduct a complete review of the existing results on IRF6 to further understand its role in the pathogenesis of NSOCs. Thus, the present authors summarised the research progress on the mechanism of IRF6 in NSOCs from both genetic and functional perspectives in this review.

Amphiphilic α-Peptoid-deoxynojirimycin Conjugate-based Multivalent Glycosidase Inhibitor for Hypoglycemic Effect and Fluorescence Imaging.

Multivalent glycosidase inhibitors based on 1-deoxynojirimycin derivatives against α-glucosidases have been rapidly developed. Nonetheless, the mechanism based on self-assembled multivalent glucosidase inhibitors in living systems needs to be further studied. It remains to be determined whether the self-assembly possesses sufficient stability to endure transit through the small intestine and subsequently bind to the glycosidases located therein. In this paper, two amphiphilic compounds, 1-deoxynojirimycin and α-peptoid conjugates (LP-4DNJ-3C and LP-4DNJ-6C), were designed. Their self-assembling behaviors, multivalent α-glucosidase inhibition effect, and fluorescence imaging on living organs were studied. LP-4DNJ-6C exhibited better multivalent α-glucosidase inhibition activities in vitro. Moreover, the self-assembly of LP-4DNJ-6C could effectively form a complex with Nile red. The complex showed fluorescence quenching effect upon binding with α-glucosidases and exhibited potent fluorescence imaging in the small intestine. This result suggests that a multivalent hypoglycemic effect achieved through self-assembly in the intestine is a viable approach, enabling the rational design of multivalent hypoglycemic drugs.

Engineered Luminescent Oncolytic Vaccinia Virus Activation of Photodynamic-Immune Combination Therapy for Colorectal Cancer.

Oncolytic virus therapy is currently regarded as a promising approach in cancer immunotherapy. It has greater therapeutic advantages for colorectal cancer that is prone to distant metastasis. However, the therapeutic efficacy and clinical application of viral agents alone for colorectal cancer remain suboptimal. In this study, an engineered oncolytic vaccinia virus (OVV-Luc) that expresses the firefly luciferase gene is developed and loaded Chlorin e6 (Ce6) onto the virus surface through covalent coupling, resulting in OVV-Luc@Ce6 (OV@C). The OV@C infiltrates tumor tissue and induces endogenous luminescence through substrate catalysis, resulting in the production of reactive oxygen species. This unique system eliminates the need for an external light source, making it suitable for photodynamic therapy (PDT) in deep tissues. Moreover, this synergistic effect between PDT and viral immunotherapy enhances dendritic cell maturation, macrophage polarization, and reversal of the immunosuppressive microenvironment. This synergistic effect has the potential to convert a "cold" into a "hot" tumor, it offers valuable insights for clinical translation and application.

Analysis of Risk Factors for Velopharyngeal Insufficiency and Palatal Fistula After Sommerlad-Furlow Palatoplasty.

This study aimed to introduce a surgery technique-Sommerlad-Furlow palatoplasty (SFP) and analyze the risk factors of velopharyngeal insufficiency (VPI) and palatal fistula after SFP. Cases after SFP under the age of 5 between 2011 and 2021 were reviewed, and the cases with complete follow-up information were included. Univariate and multivariate logistic regression were used to evaluate the effects of surgical age, surgery technique, surgeon's experience, and cleft type on velopharyngeal function and the occurrence of palatal fistula. SFP is a safe and effective procedure to increase the palatal length and reconstruct the levator veli palatini sling. The speech outcome after SFP was associated with cleft type and age at operation. Age = 1.285 years is the best cutoff value. The fistula occurrence was associated with cleft type only.

Tumor-targeted delivery of copper-manganese biomineralized oncolytic adenovirus for colorectal cancer immunotherapy.

Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. STATEMENT OF SIGNIFICANCE: Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, hypoxia effect, and administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy.

Preliminary study on reliability and validity of the Chinese version of the Asher-McDade aesthetic index.

OBJECTIVES: This study aims to test the reliability and validity of the Chinese version of the Asher-McDade aesthetic index and clarify its feasibility for the postoperative outcome evaluation of cleft lip in China. METHODS: The Chinese version of the Asher-McDade aesthetic index was established through translation, back translation, debugging, and pre-survey. Eighty postoperative photographs of patients with cleft lip admitted to the West China Hospital of Stomatology, Sichuan University were included. Ten healthcare professionals, including surgeons, nurses, and students, in the department of cleft lip and palate surgery finished the index to test its reliability and validity. RESULTS: The Cronbach's alpha coefficient and retest reliability of this index are 0.804 and 0.895, respectively. The item-level content validity index (I-CVI) and scale-level content validity index ave-rage (S-CVI/ave) of the index are 1.000 and 0.95, respectively. For this index, the Kaiser-Meyer-Olkin (KMO) test score is 0.706, the χ2 value of Bartlett's test for the consistency of the index is 962.260 (P<0.01), and the cumulative variance contribution rate is 63.095%. CONCLUSIONS: The Chinese version of the Asher-McDade aesthe-tic index has good reliability and validity and is applicable to the professional evaluation of the effect of postoperative photographs in Chinese patients with cleft lip.

Cost-effectiveness of screening for amblyopia among kindergarten children in China.

Objective: Current cost-effectiveness analyses of amblyopia screening are mainly from western countries. It remains unclear whether it is cost-effective to implement a preschool amblyopia screening programme in China. Our study aimed to evaluate the cost-effectiveness of a hypothetical kindergarten-based amblyopia screening versus non-screening among 3-year-old children. Methods: We developed a decision tree combined with a Markov model to compare the cost and effectiveness of screening versus non-screening for 3-year-old children from a third-party payment perspective. The primary outcomes were quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Costs were obtained from expert opinions in different regions of China. Transition probabilities and health utilities were mainly based on published literature and open sources. Sensitivity analyses were performed to assess the impact of parameters' uncertainty on results. Results: Base-case analysis demonstrated that the ICER of screening versus non-screening was $17,466/QALY, well below the WTP threshold ($38,223/QALY) for China. One-way sensitivity analysis showed that the prevalence of amblyopia, the transition probability per year from untreated amblyopia to healthy, and the discount rate were the top three factors. The likelihood of cost-effectiveness of screening compared with non-screening was 92.56%, according to probabilistic sensitivity analysis. Scenario analysis also indicated that ICER was lower than the WTP threshold even if the time horizon was shortened or the screening was delayed to the age of 4 or 5. Conclusions: Amblyopia screening could be considered a cost-effective strategy compared to non-screening for 3-year-old children in China. Screening for children at the age of 4 or 5 may even yield better results.

Dry eye symptoms and health-related quality of life among Chinese individuals: a national-based study.

AIMS: To assess the impact of dry eye symptoms (DESs) on health-related quality of life (HRQOL) among Chinese residents. METHODS: A total of 21 916 participants were involved in this nationwide cross-sectional study. All of them completed the Ocular Surface Disease Index-6 and the five-level European Quality of Life 5-Dimensional (EQ-5D) Questionnaire to assess the severity of DES and HRQOL, respectively. Multiple linear regression models were used to explore the associations of DES with EQ-5D health utility score (HUS) and visual analogue scale (VAS) score. We used logistic regression models to assess the relationships between DES and self-reported problems in the EQ-5D dimensions. RESULTS: Overall, 43.6% of participants reported DESs. Of them, 2511 (11.5%) were with mild symptoms, 2762 (12.6%) were with moderate symptoms and 4288 (19.6%) were with severe symptoms. Both EQ-5D HUS and VAS score were significantly negatively associated with the severity of DES. The difference in HUS between patients with no symptoms and severe symptoms (0.085) was larger than the minimally clinical important difference for EQ-5D. The loss in HRQOL was greater for patients with severe DES than those just with other comorbidities. Participants with DES had a significantly higher risk of reporting problems in all five EQ-5D dimensions, especially in pain/discomfort and anxiety/depression for patients with mild or moderate symptoms and in mobility, self-care and usual activities for severe patients. CONCLUSION: Patients with more severe DES tend to have lower HRQOL. Effective interventions targeted at different HRQOL dimensions should be taken according to the severity of DES.

Genetic association and functional validation of ZFP36L2 in non-syndromic orofacial cleft subtypes.

BACKGROUND: Non-syndromic orofacial cleft (NSOC) is one of the most common craniofacial malformations with complex etiology. This study aimed to explore the role of specific SNPs in ZFP36L2 and its functional relevance in zebrafish models. METHODS: We analyzed genetic data of the Chinese Han population from two previous GWAS, comprising of 2512 cases and 2255 controls. Based on the Hardy-Weinberg Equilibrium (HWE) and minor allele frequency (MAF), SNPs in the ZFP36L2 were selected for association analysis. In addition, zebrafish models were used to clarify the in-situ expression pattern of zfp36l2 and the impact of its Morpholino-induced knockdown. RESULTS: Via association analysis, rs7933 in ZFP36L2 was significantly associated with various non-syndromic cleft lip-only subtypes, potentially conferring a protective effect. Zebrafish embryos showed elevated expression of zfp36l2 in the craniofacial region during critical stages of oral cavity formation. Furthermore, Morpholino-induced knockdown of zfp36l2 led to craniofacial abnormalities, including cleft lip, which was partially rescued by the addition of zfp36l2 mRNA. CONCLUSION: Our findings highlight the significance of ZFP36L2 in the etiology of NSOC, supported by both human genetic association data and functional studies in zebrafish. These results pave the way for further exploration of targeted interventions for craniofacial malformations.