BACKGROUND: An increased prevalence of cleft lip and/or palate (CL/P), a major congenital anomaly, has been observed in the offspring of women with elevated body mass index (BMI) before pregnancy. Likewise, gestational comorbidities, such as hypertension and diabetes mellitus, also increase the risk of CL/P; however, the risk linked to the coexistence of these conditions in women with higher BMI on birth prevalence of CL/P remains unclear. This study focused on the combined effects of a high BMI before pregnancy and gestational comorbidities on the birth prevalence of CL/P. METHODS: Among 98,373 live births from the Japan Environment and Children's Study (JECS), a nationwide birth cohort, 255 mothers of infants with CL/P (74, 112, and 69 infants born with cleft lip, cleft lip and palate, and isolated cleft palate, respectively) were included in the analyses. The association of CL/P birth prevalence with pre-pregnancy BMI and gestational comorbidities (hypertension and diabetes) was examined using multivariate logistic regression analyses after multiple imputations, with adjustments for several maternal (age at delivery, smoking habits, and alcohol intake) and child-related (sex and prevalence of other congenital diseases) variables, obtained through medical record transcriptions and self-reports on JECS transcription forms. RESULTS: Higher prevalence rates of overweight, gestational hypertension, and gestational diabetes mellitus were found in mothers of infants with CL/P (16.1%, 6.3%, and 4.7%, respectively) than in the control group (10.4%, 3.1%, and 3.1%, respectively). The odds ratio [95% confidence interval] for childbirth with CL/P was increased in mothers with high BMI before pregnancy (1.58 [1.11-2.24]). Furthermore, gestational hypertension and diabetes coexisting with high BMI additionally increased the odds ratios for childbirth with CL/P (2.91 [1.28-6.61] and 2.12 [0.87-5.19], respectively). CONCLUSION High maternal BMI, particularly when accompanied by gestational hypertension, was significantly associated with an increased prevalence of childbirth with CL/P.
Humans ; Female ; Cleft Lip/etiology* ; Cleft Palate/etiology* ; Pregnancy ; Japan/epidemiology* ; Prevalence ; Body Mass Index ; Adult ; Male ; Infant, Newborn ; Comorbidity ; Diabetes, Gestational/epidemiology* ; Risk Factors ; Young Adult ; Birth Cohort

OBJECTIVES: To analyze the trends of disease burden of lip and oral cancers in East Asia from 1990 to 2021 and its future projections. METHODS: We used the Global Burden of Disease 2021 database to conduct a comprehensive analysis of disease burden data from China (including Taiwan Province of China), Japan, Republic of Korea, Democratic People's Republic of Korea and Mongolia. The data were stratified by age, gender and major risk factors, and a Bayesian age-period-cohort model was employed to predict the future trends. RESULTS: From 1990 to 2021, the burden of lip and oral cancers in East Asian countries exhibited a steady increase. Taiwan Province of China experienced the most significant increases in incidence, prevalence, mortality, and disability-adjusted life years (DALYs), while Mongolia saw a decline in both mortality and DALYs. In 2021, Taiwan Province of China reported the highest rates of lip and oral cancer incidence (27.50 per 100 000), prevalence (137.92 per 100 000), mortality (9.59 per 100 000), and DALYs (292.07 person-years per 100 000), particularly among male and elderly populations. Tobacco use and alcohol consumption significantly exacerbated the disease burden in Taiwan Province of China and Japan. Future projections indicate that the incidence and prevalence of lip and oral cancer in China (excluding Taiwan Province of China) will continue to rise, while their mortality rates are expected to decline in most regions, except for Taiwan Province of China and Democratic People's Republic of Korea. CONCLUSIONS By the year 2035, the disease burden of lip and oral cancers in East Asia is expected to continue to increase, especially in Taiwan Province of China. To address this challenge, it is essential to implement effective measures to control major risk factors, promote early screening, and ensure equitable distribution of healthcare resources.
Humans ; Mouth Neoplasms/epidemiology* ; Incidence ; Lip Neoplasms/epidemiology* ; Asia, Eastern/epidemiology* ; Male ; Disability-Adjusted Life Years ; Prevalence ; Female ; Forecasting ; Risk Factors ; Cost of Illness ; Middle Aged ; Global Burden of Disease ; Aged ; Bayes Theorem

Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA⁺ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
Humans ; Neutrophils/metabolism* ; Single-Cell Analysis ; Lip Neoplasms/genetics* ; Hyperthermia, Induced/methods* ; Microwaves/therapeutic use* ; Transcriptome ; Carcinoma, Squamous Cell/immunology* ; Tumor Microenvironment

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

OBJECTIVES: This study aims to explore the association between single nucleotide polymorphisms (SNPs) loci near the haplotype region hg19 chr9:100560865-100660865 of the forkhead box E1 (FOXE1) gene and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P) in western Han Chinese population. METHODS: In the first stage, our study recruited 159 NSCL/P patients and performed targeted region sequencing to screen SNPs loci near the haplotype region of the FOXE1 gene associated with NSCL/P. In the second stage, we selected 21 common SNPs and re-enrolled 1 000 non-syndromic cleft lip only (NSCLO) patients, 1 000 non-syndromic cleft palate only (NSCPO) patients, and 1 000 normal controls to verify the association. PLINK software was used to perform Hardy-Weinberg equilibrium (HWE) test. Association analysis for common variants, gene burden analysis for rare mutations, and function prediction of SNPs with non-synonymous mutations were performed using Mutation Taster and other software programs. RESULTS: In the first stage, 126 variants, including 76 single nucleotide variants and 50 insertion-deletions were identified. All the included SNPs confirmed to HWE, and the results of gene burden analysis and prediction of functional harmfulness for rare variants were not statistically significant. Association analysis showed that rs13292899 of the FOXE1 gene was significantly associated with NSCL/P (P=1.85E-27) and was also correlated with NSCLO (P=6.41E-23) and non-syndromic cleft lip with cleft palate (NSCLP) (P=2.36E-15) subtypes. In the validation phase, rs79268293 (P=0.013, P=0.022), rs10983951 (P=0.009 2, P=0.007 6), rs117227387 (P=0.009 2, P=0.007 6), rs3758250 (P=0.009 2, P=0.007 6), and rs116899397 (P=0.009 2, P=0.007 6) were significantly associated with NSCLO and NSCPO; rs13292899 (P=0.008 5), rs74606599 (P=0.008 3), rs143226042 (P=0.008 3), and rs117236550 (P=0.01) were associated with the occurrence of NSCLO; and rs12343182 (P=0.008 7), rs10119760 (P=0.012), rs10113907 (P=0.012), and rs13299924 (P=0.012) were associated with the occurrence of NSCPO. CONCLUSIONS This study found a new susceptible SNP rs13292899 of the FOXE1 gene that is closely associated with NSCL/P and NSCLO subtype and 13 other SNPs associated with NSCLO or NSCPO.
Female ; Humans ; Male ; China ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Forkhead Transcription Factors/genetics* ; Haplotypes ; Polymorphism, Single Nucleotide ; East Asian People/genetics*

OBJECTIVES: This study aims to investigate factors influencing dental arch development in patients aged 0-6 years with cleft palate after Sommerlad-Furlow (SF) palatoplasty. METHODS: A total of 183 patients who underwent primary SF repair for cleft lip and palate before 18 months of age were included. Follow-ups were conducted at different ages, and digital dental casts of the maxillary dental arch were obtained using 3-matic Research 12.0 software. The length and width of the dental arch and palate were measured to explore developmental changes in the maxillary dental arch of the patients after the procedure. The study also investigated the influence of gender, age, cleft palate type, and relaxation incision on maxillary dental arch development. RESULTS: After SF, maxillary dental arch measurements showed statistically significant differences between children aged 0-2 years and those aged 3-6 years (P<0.05). However, no statistically significant differences were observed among different age groups within the 3-6 years range. Statistically significant differences were detected between males and females, with males having greater width of the posterior dental arch and palate (P=0.001) and shorter length of the anterior dental arch and entire dental arch (P<0.05). The unilateral cleft lip and palate group had shorter dental arch length (P<0.01) and wider posterior palate (P<0.01) than the cleft palate only group. Maxillary dental arch measurements had no statistically significant differences between groups with or without a relaxing incision. CONCLUSIONS Gender and age influence the width of the maxillary dental arch in children aged 0-6 years after SF, while age and cleft palate type affect dental arch length.
Humans ; Child, Preschool ; Male ; Cleft Palate/surgery* ; Female ; Child ; Infant ; Dental Arch/growth & development* ; Maxilla/growth & development* ; Cleft Lip/surgery* ; Age Factors ; Sex Factors ; Palate/surgery* ; Infant, Newborn

The unilateral cleft lip repair surgery has undergone over a century of development, marked by achievements and difficulties. Although the development of the methods for cleft lip repair has passed the period of rapid advancement, there remains an urgent need in clinical practice to further improve these methods in order to enhance clinical outcomes. This article aims to improve cleft lip repair methods by analyzing and elaborating on various aspects, including the attributes of cleft lip repair, the shift in concepts of cleft lip repair, innovations in surgical techniques, technical improvements, and classifications and repair methods for correcting secondary deformities. The analysis is based on the author's research and experience.
Cleft Lip/surgery* ; Humans ; Plastic Surgery Procedures/methods* ; Surgical Flaps

OBJECTIVE: To investigate the effectiveness of comprehensive rhinoplasty with autogenous costal cartilage grafting and prosthesis augmentation rhinoplasty in the treatment of secondary nasal deformity with saddle nasal deformity after cleft lip surgery. METHODS: The clinical data of 96 patients with secondary nasal deformity with saddle nasal deformity after cleft lip surgery between September 2008 and January 2019 were retrospectively analyzed. There were 17 males and 79 females with an average age of 25.6 years (range, 17-38 years). Autogenous costal cartilage grafts were used to construct stable nasal tip framework and enhance the strength of alar cartilage. Nasal dorsum prostheses (39 cases of bulge, 45 cases of silicone prosthesis) or autogenous costal cartilage (12 cases) were used for comprehensive rhinoplasty. Visual analogue scale (VAS) score was used to evaluate the postoperative satisfaction subjectively, and nasal alar height symmetry index, nasal alar width symmetry index, nasal dorsum central axis deviation angle, and nasal columella deviation angle were calculated to evaluate objectively before and after operation. RESULTS: All patients were followed up 6 months to 8 years, with an average of 13.4 months. Nasal septal hematoma occurred in 3 patients after operation, which was improved after local aspiration and nasal pressure packing. Two cases had mild deformation of the rib cartilage graft of the nasal dorsum, one of which had no obvious deviation of the nasal dorsum and was not given special treatment, and one case underwent the cartilage graft of the nasal dorsum removed and replaced with silicone prosthesis. The incisions of the other patients healed by first intention, and there was no complication such as postoperative infection and prosthesis displacement. The nasal alar height symmetry index, nasal alar width symmetry index, nasal dorsum central axis deviation angle, and nasal columella deviation angle significantly improved after operation when compared with preoperative ones ( P<0.05). Postoperative subjective satisfaction evaluation reached the level of basic satisfaction or above, and most of them were very satisfied. CONCLUSION Comprehensive rhinoplasty using autologous rib cartilage grafting to construct a stable nasal tip support, combined with dorsal nasal prosthesis or autologous cartilage implantation, can achieve good effectiveness on secondary nasal deformity with saddle nasal deformity after cleft lip surgery.
Male ; Female ; Humans ; Adult ; Rhinoplasty ; Cleft Lip/surgery* ; Retrospective Studies ; Nose/surgery* ; Nasal Septum/surgery* ; Nasal Cartilages/surgery* ; Silicones ; Treatment Outcome

Background: One of the early problems that children born with cleft lip and palate encounter is difficulty in feeding. This affects the child’s nutritional needs and the timing of the surgical intervention. Information on the appropriate feeding methods for children with cleft lip and palate will enable mothers to feed their babies properly and facilitate the implementation of appropriate interventions. Objectives: The study described the feeding problems experienced by children with cleft lip and palate (CLP), and cleft palate (CP) ages 0-24 months, the feeding methods most preferred by Filipino mothers, the methods they found most useful, and the mothers’ reactions to the feeding issues their children face. Methods. The research is a pilot study which used a quantitative, cross-sectional, descriptive mixed method design. Thirty-two (32) mothers of children with cleft lip and palate, and cleft palate answered an 11-item online survey and participated in focused interviews from January to June 2022. Inferential statistics was used specifically frequency distribution to describe the data, and Fishers’ Exact Test and Pearson’s Chi-Square Test were used to analyze the data quantitatively to determine the significant association between the variables identified. Results: Results showed that the feeding problems encountered by the children included nasal regurgitation, sucking, aspiration of liquids, latching on nipples, and swallowing. Mothers preferred to use regular feeding bottles (24.3%), specialized feeding bottles for children with cleft (21.6%), breast feeding and dropper (17.6%), syringe (9.5%), cup (6.8%), and spoon feeding (2.7%) methods. They also mentioned that they found the following feeding methods to be the most useful, regular feeding bottles (32.7%), specialized feeding bottles for cleft (23.1%), breast feeding (11.5%), spoon and dropper feeding (7.7%), and syringe feeding (1.9%). Conclusion The feeding problems experienced by Filipino children with CLP and CP mirror those that have been reported in other studies. The study revealed that mothers still prefer to use the traditional regular feeding bottles in feeding their babies and found this to be the most useful. Maternal reactions of the participants to the cleft condition and its feeding issues are similar to reported studies in other countries. The internet has been the primary source of information on cleft and feeding of the participants in the study.
Feeding Methods ; Cleft Lip ; Palate

Objective: To investigate the characteristics of electromyography (EMG) signals and the starting threshold voltages of the orbicularis oris muscles (OOM) in healthy rhesus monkeys under different muscle movement conditions. Methods: The EMG signals and the starting threshold voltages at different time points in 4 healthy rhesus monkeys were acquired and recorded with EMG device and evoked potentiometer. The voltage amplitude variation of EMG signals was analyzed, and the voltage amplitude range of EMG signals at the beginning of OOM contraction was established. The data were statistically analyzed by one-way ANOVA. Results: The EMG of OOM in healthy monkeys in the quiet, natural and continuous mouth-closed state was linear and relatively stable, and the absolute value fluctuated between 15 and 50 μV. The EMG waveform increased rapidly during the natural lip contraction movement, and its amplitude fluctuated greatly, with the highest absolute value of the peak value reaching hundreds of microvolts. The amplitude of EMG induced by continuous mouth closure was more than thousands of microvolts. There was no significant difference in EMG amplitudes of OOM in the healthy rhesus monkey under quiet and continuous lip closure at different time points (P>0.05). There was no significant difference in threshold voltages in the state of natural lip contraction of bilateral OOM at different time points (average range: 57.17-57.47 μV) in the healthy rhesus monkeys (P>0.05). There was no significant difference in threshold voltages of OOM induced by bilateral OOM at different time points(average range: 55.38-55.99 μV) in the healthy rhesus monkeys(P>0.05). There were significant differences in the absolute values of EMG amplitudes of OOM between the three lip movement modes: (30.67±8.72) μV in quiet and natural continuous lip closure (475.12±54.72) μV in natural lip contraction, and (921.22±312.79) μV in the induced persistent lip closure, with t values of -8.48, -9.35 and -5.01 respectively, all P<0.001. Conclusions: The EMG signals of OOM show different characteristics under different muscle movement conditions, which can be used as a basis for computer to judge and recognize the movement conditions of OOM. The upper limits of the EMG threshold voltage values of OOM under different motion states are 55-60 μV.
Animals ; Lip ; Macaca mulatta ; Facial Muscles ; Electromyography