Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formatio...Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formation. FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs (NSOFCs). Here, we report two rare heterozygous variants (p.P441T and p.G565R) in FLNB in two unrelated hereditary families with NSOFCs. Bioinformatics analysis suggests that both variants may disrupt the function of FLNB. In mammalian cells, p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB, suggesting that they are loss-of-function mutations. Immunohistochemistry analysis demonstrates that FLNB is abundantly expressed during palatal development. Importantly, Flnb^(−/−) embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.展开更多
A novel type of chiral molecular clefts consisting of a rigid deoxycholic acid methyl ester backbone and chiral unsymmetrically disubstituted urea side chain have been designed and synthesized. All these new receptor...A novel type of chiral molecular clefts consisting of a rigid deoxycholic acid methyl ester backbone and chiral unsymmetrically disubstituted urea side chain have been designed and synthesized. All these new receptors 3a^c and the corresponding key intermediates 1a^c and 2a^c are new compounds, their structures were confirmed by 1HNMR, IR, MS spectra and elemental analysis. These molecular clefts showed binding ability for halide anions.展开更多
Human orofacial clefts (OFCs) are congenital anomalies that result from the breakdown of normal mechanisms that regulate the formation of the human face. They could be syndromic or non-syndromic, with a global inciden...Human orofacial clefts (OFCs) are congenital anomalies that result from the breakdown of normal mechanisms that regulate the formation of the human face. They could be syndromic or non-syndromic, with a global incidence of 1:700 per live births. Environmental and genetic factors are thought to play various roles in the aetiology of OFCs. This study seeks to establish the diversity, distribution and pattern of inheritance of OFCs as well as environmental and other risk factors associated with OFCs in a Ghanaian population. A family-based, descriptive cross-sectional study that employed an interview-based survey questionnaire was used to obtain information from 467 families with history of OFCs. We employed chi-square statistics to analyse the data and used graphs to interpret the data. All previously reported subphenotypes of OFCs were observed by the present study. Clinically, about 12% of clefts in the study population were syndromic. The most common syndromic forms observed were Pierre Robin Sequence, cleft-with-club foot abnormalities and Van der Woude Syndrome. Only about 5% of clefts in the study cohort were familial. The study also established that lower level of education of parents, poverty, late antenatal care and dietary folate deficiency are major environmental factors associated with clefts in the Ghanaian population. In conclusion, OFCs are non-randomly distributed in Ghana and folate deficiency could likely be a source of genetic mutations and “epimutations” that cause OFCs, since folate is essential for DNA methylation, replication and repair as well as histone modification.展开更多
<strong>Introduction: </strong>The management of nasolabial-palatal clefts in precarious environments is one of the topics most addressed by many humanitarian missions, especially in Africa and Asia. The a...<strong>Introduction: </strong>The management of nasolabial-palatal clefts in precarious environments is one of the topics most addressed by many humanitarian missions, especially in Africa and Asia. The aim of our study was to propose a humanitarian and not expensive care to the patients presenting with facial clefts during the fairgrounds in disadvantaged areas. <strong>Patients and</strong> <strong>Method:</strong> We carried out a prospective study on 32 patients who were operated with very limited means during the mobile clinics inside Togo during the year 2013. These patients were followed over a period of one year after their surgery. Included in our series were native patients with facial clefts, who had no means of managing their condition, and who therefore needed humanitarian support. We have reported the clinical history of some patients to illustrate our results. <strong>Results:</strong> Our study included 32 children, including 15 boys and 17 girls, with a sex ratio of around 1. The average age of patients was 5 years, with extremes of 6 months and 13 years. We performed 13 clefts (including 12 unilateral clefts and 1 bilateral cleft), 17 clefts palate (including 12 unilateral clefts and 5 bilateral clefts), and 2 velar clefts. We described the clinical history of a few patients in this humanitarian setting and showed the surgical results obtained.展开更多
Purpose: The evaluation of the patients with clefts;the number, type, distribution by gender, etiological factors in Aegean region in Turkey between the years 2000 to 2011. Material and Method: The patients with cleft...Purpose: The evaluation of the patients with clefts;the number, type, distribution by gender, etiological factors in Aegean region in Turkey between the years 2000 to 2011. Material and Method: The patients with clefts who referred to Ege University from different cities were evaluated. The number of the clefts, the type of the clefts, and the causative etiological factors which were known, were recorded for each year separately, from 2000 to 2011. At the same time, the distribution of the gender was made for each year. Chi-square test is used for the statistical evaluation. Results: According to the results of the study, the numbers of the patients with clefts were increased day by day. Totally 741 (49.6% female, 50.4% male) patients with clefts were identified. Unilateral complete cleft lip and palate appeared in the left side was seen more in males (23.8%), while seconder palate cleft was seen more in females (16.7%). Drugs, which were used in the first trimester of the pregnancy, were the most seen etiological factors for the clefts (42.5%), while genetic was 23.3% only. Conclusion: The prevention for one of the mostly seen congenital anomaly;cleft lip and palate is still unknown. For this reason, the determination of the newborn babies with cleft lip and palate has an important role in order to give these patients more effective treatment.展开更多
A rapid, safe, and efficient method for the synthesis of novel molecular clefts based on deoxycholic acid was reported. Seven new molecular clefts have been synthesized in good yields （89-98%）. This method proved to...A rapid, safe, and efficient method for the synthesis of novel molecular clefts based on deoxycholic acid was reported. Seven new molecular clefts have been synthesized in good yields （89-98%）. This method proved to be extremely simple and highly efficient. The structures of these receptors were confirmed by 1H NMR, IR, MS spectra and elemental analysis. 2007 Zhi Gang Zhao. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.展开更多
Oral clefts, the most frequent congenital birth defects in humans, are multifactorial disorders caused by genetic and environmental factors. Epidemiological studies point to different etiologies underlying the oral cl...Oral clefts, the most frequent congenital birth defects in humans, are multifactorial disorders caused by genetic and environmental factors. Epidemiological studies point to different etiologies underlying the oral cleft phenotypes, cleft lip(CL),CL and/or palate(CL/P) and cleft palate(CP). More than 350 genes have syndromic and/or nonsyndromic oral cleft associations in humans. Although genes related to genetic disorders associated with oral cleft phenotypes are known, a gap between detecting these associations and interpretation of their biological importance has remained. Here, using a gene ontology analysis approach, we grouped these candidate genes on the basis of different functional categories to gain insight into the genetic etiology of oral clefts. We identified different genetic profiles and found correlations between the functions of gene products and oral cleft phenotypes. Our results indicate inherent differences in the genetic etiologies that underlie oral cleft phenotypes and support epidemiological evidence that genes associated with CL/P are both developmentally and genetically different from CP only, incomplete CP, and submucous CP. The epidemiological differences among cleft phenotypes may reflect differences in the underlying genetic causes. Understanding the different causative etiologies of oral clefts is important as it may lead to improvements in diagnosis, counseling, and prevention.展开更多
Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of envir...Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of environmental and genetic factors. This paper provides a review of recent progress in defining the genetic causes of NSCLP. Methods: A literature review was conducted on the Medline data by searching for the following keywords: genes, non-syndromic cleft lip-palate, and genetics of clefts lip-palates, until January 2018. Results: Various genes are identified in different population and country, with the study using case parent’s trio. The aim of this study contributes to review relative gene which has been identify in non-syndromic cleft lip and palate, and to help to have a better understanding of the inheritance pattern of this pathology and the prevention of genetic disease. Conclusion: Although three major genes have been confirmed, the genetic research is necessary to provide an understanding of the pathophysiology of the clefts lip-palates.展开更多
Background: The Ghana Expanded Programme on Immunisation recommends that children receive Bacillus Calmette-Guerin (BCG) and Oral Polio Vaccine (OPV) at birth;three doses of Penta vaccine and OPV at 6, 10 and 14 weeks...Background: The Ghana Expanded Programme on Immunisation recommends that children receive Bacillus Calmette-Guerin (BCG) and Oral Polio Vaccine (OPV) at birth;three doses of Penta vaccine and OPV at 6, 10 and 14 weeks of age;and measles vaccine at 9 months of age. Aim/Objective: To evaluate the immunisation status of children born with orofacial clefts who visited the KATH multidisciplinary Cleft clinic. Methodology/Statistics: The study was a descriptive study with a cross-sectional design. The methodology consisted of in-person interviews of mothers of children born with cleft lip and palate reporting at KATH Cleft clinic. Interview guides were used for mothers who could not read. Mothers who were literate and as such could answer the questions directly were given questionnaires to fill. Result: It was reported that of the 83 children included, 47 (57%) had been fully vaccinated and on time, 24 (29%) had been fully vaccinated but delayed and 12 (14%) had not been vaccinated at all. Children with isolated cleft palate and macrostomia were fully vaccinated on time (77.3% and 100%, respectively) as compared to those with combined cleft lip and palate (43.3%) and isolated cleft lip (50.0%). The majority (77%) of the mothers who either had not vaccinated their children or had delayed in vaccinating them attributed stigmatisation as the main cause. Most of the mothers (95%) had knowledge of immunisation. About two-thirds of the mothers (65%) agreed that establishing an immunisation centre at the cleft clinic is the best way to improve immunisation rate among children with orofacial clefts. Conclusion: The study showed that the percentage of children with orofacial cleft who visited the KATH Cleft Clinic and were vaccinated on time was above the national average. Cleft palates were more vaccinated and on time than cleft lips. According to the children’s mothers, lack of timely vaccination was mainly due to the stigma associated with clefts in their societies.展开更多
Background: In developing countries, charity cleft surgical mission is always operated by sporadic surgical teams without systematic follow up and quality assurance. In the past few decades, many mission projects have...Background: In developing countries, charity cleft surgical mission is always operated by sporadic surgical teams without systematic follow up and quality assurance. In the past few decades, many mission projects have been held regularly in China. The purpose of this audit was a retrospective analysis of a 9-year cleft lip and palate charity project operated in a tertiary hospital in China Shenzhen Area to evaluate perioperative and postoperative complications. Nevertheless, understanding the risk profile is essential for establishing a sustainable in-house cleft service in Shenzhen. Methods: A detailed analysis of hospital centralized record in the The University of Hong Kong-Shenzhen Hospital (HKUSZH) was reviewed since the first charity project held in 2015. The parameters of this audit were focused on perioperative complications including anesthesia related problems, early postoperative complications in patients who underwent primary or secondary cleft surgeries. A total of 430 consecutive admitted cases of 311 non-syndromic cleft lip & palate patients were enrolled into the charity project from June 2015 to July 2024. The main anesthesia related complications that occurred during general anesthesia were respiratory tract problems, while intraoperative complication was excessive bleeding, so as wound local infection and reaction were the main early postoperative complications. Results: In our 9-year clinical audit of 430 cleft lip and palate charity surgeries in Shenzhen, we observed no mortalities and a anesthesia-related complication rate of 1.16%. Specific intraoperative complications included excessive bleeding, while early postoperative issues were dominated by wound infections. The fistula rate of 18.7% post palate repair and the average hospital stay of 3.71 days complete the profile of our surgical outcomes. These data underscore the project’s efficacy and offer a reference for international cleft missions aiming for safe and efficient surgical care. Conclusions: This study provides a thorough data review of the complications in the past 9 years charity missions for cleft lip and palate surgery in a well-structured hospital infrastructure and logistic support by local surgical team. There were no perioperative or postoperative death during the study period and the overall short-term complication rate was low. Therefore, it could be a reference model for other international cleft mission in developing country for a safe and efficient service in future.展开更多
Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology i...Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection.A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring.However,the precise relationship remains unclear.In this study,the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P.gingivalis injected intravenously and orally into pregnant mice.We investigated an obvious increasing CP(12.5%)in sonicated P.gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium.Then glycolysis and H4K12 lactylation(H4K12la)were detected to elevate in both mouse embryonic palatal mesenchyme(MEPM)cells and macrophages under P.gingivalis exposure which further promoted the transcription of metallopeptidase domain17(ADAM17),subsequently mediated the shedding of transforming growth factor-beta receptor 1(TGFBR1)in MEPM cells and mer tyrosine kinase(MerTK)in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate,eventually caused abnormalities in palate fusion and ossification.The abnormal efferocytosis also led to a predominance of M1 macrophages,which indirectly inhibited palatal osteogenesis via extracellular vesicles.Furthermore,pharmacological ADAM17 inhibition could ameliorate the abnormality of P.gingivalis-induced abnormal palate development.Therefore,our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.展开更多
Cleft palate is a common congenital malformation of the maxillofacial region,and its postoperative speech disorders(such as hypernasality,nasal emission,and articulation errors)can significantly impact patients’commu...Cleft palate is a common congenital malformation of the maxillofacial region,and its postoperative speech disorders(such as hypernasality,nasal emission,and articulation errors)can significantly impact patients’communication abilities and psychological well-being.Traditional speech-language therapy faces challenges such as insufficient personalization of training methods,limited scenarios,and low patient compliance,making it inadequate for long-term rehabilitation needs.The innovative intervention model of a mobile interactive platform combined with games and picture books,through immersive experiences,instant feedback,and engaging designs,holds promise for enhancing patient participation and overall treatment outcomes.Therefore,this paper provides a comprehensive review from five perspectives:the pathological mechanisms and treatment needs of cleft palate speech disorders,the advantages of games and picture books as carriers in cleft palate speech therapy,the technological implementation of mobile interactive platforms,clinical application effects,and current challenges and limitations.The aim is to offer valuable insights for clinical practice and technological development in cleft palate speech rehabilitation.展开更多
Background: Reconstruction of Nasal Tip Columella (NTC) subunits is one of the most challenging aspects in functional aesthetic rhinoplasty. Moreover, racial variation for Asian nose rhinoplasty could even demand soph...Background: Reconstruction of Nasal Tip Columella (NTC) subunits is one of the most challenging aspects in functional aesthetic rhinoplasty. Moreover, racial variation for Asian nose rhinoplasty could even demand sophistication of tip and columella strut graft infrastructure enhancement. Various autogenous graft options such as 6th costal cartilage, septal cartilage and conchal cartilage are very commonly considered whilst the 10th costal cartilage is scarcely reported. Objective and Method: The purpose of this manuscript is to illustrate the detailed operative steps to harvest the 10th costal cartilage for infrastructural grafting at NTC subunits by a case illustration. The pros and cons of different cartilage options will be discussed, particularly its application in cleft nose rhinoplasty in Chinese patient. We have adopted the 10th rib as the key option for NTC reconstruction in 11 cases of Chinese cleft secondary rhinoplasty since 2019 and have achieved good and stable results without complications. Conclusion: The 10th costal cartilage is one of the best options in Nasal Tip Columella subunits reconstruction, particularly in complex cleft nose or failure revision aesthetic rhinoplasty cases, due to its safety of harvesting, and the sufficient quality and quantity of grafting materials it provides for simultaneous adjunctive augmentation purpose.展开更多
Objective To observe the clinical efficacy of fire needling and bloodletting at cleft points for acute gouty arthritis, and to explore its functional mechanism. Methods Thirty-five patients with acute gouty arthritis ...Objective To observe the clinical efficacy of fire needling and bloodletting at cleft points for acute gouty arthritis, and to explore its functional mechanism. Methods Thirty-five patients with acute gouty arthritis were enrolled into this study, and fire needling and bloodletting with 10 mL/ time were applied at cleft points of corresponding meridians and collaterals at the affected side. The treatment was conducted for once every other day, and treatment for three consecutive times was needed. Serum uric acid （UA） and pain score were tested in patients before treatment and on the 6th day after treatment, follow-up visit for 3 months was performed in patients who stopped treatment, and recurrence rate was calculated. Results Budzyuski 6-point behavioral rating scale was applied to score pain. T-test was conducted on mean and standard deviation of pain score before treatment （4.09 ＋ 0.82） and after treatment （1.14 ＋ 1.33）, showing that the difference was significant （P〈0.05）; t-test was also conducted on mean and standard deviation of serum UA before treatment [（555.34 ＋ 53.09） pmol/L] and after treatment [（414.23 ＋ 67.04） pmol/L], showing that the difference was significant （P〈0.05）; among the 35 patients with acute gouty arthritis, 14 patients were cured （40.0%）, improvement was found in 19 patients （54.3%）, and effectiveness was found in 33 patients （94.3%）. Based on follow-up visit for 3 months in 33 patients with efficacy, recurrence was found in 3 patients （9.1%）. Conclusion Fire needling and bloodletting at cleft points is an effective method in treatment of acute gouty arthritis with significant analgesic effect, efficacy of reducing serum UA, high cure rate and low recurrence rate, which is worth of being generalized clinically.展开更多
Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and pal...Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and palate develop in a very characteristic way. For ultrasonographers involved in screening these patients it is crucial to have a thorough understanding of the embryology of the face. This could help them to make a more accurate diagnosis and save time during the ultrasound. Subsequently, the current postnatal classification will be discussed to facilitate the communication with the CP teams.展开更多
基金supported by the National Natural Science Foundation of China(No.81870747,82170916,81900984,and 82001030)the Fundamental Research Funds for the Central Universities(PKU2022XGK001)+2 种基金Natural Science Foundation of Beijing Municipality(7182184)Xi'an“Science and Technology+”Action Plan-Medical Research Project(20YXYJ0010[1])the Fundamental Research Funds for the Central Universities(xzy012020110).
文摘Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formation. FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs (NSOFCs). Here, we report two rare heterozygous variants (p.P441T and p.G565R) in FLNB in two unrelated hereditary families with NSOFCs. Bioinformatics analysis suggests that both variants may disrupt the function of FLNB. In mammalian cells, p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB, suggesting that they are loss-of-function mutations. Immunohistochemistry analysis demonstrates that FLNB is abundantly expressed during palatal development. Importantly, Flnb^(−/−) embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.
基金the National Natural Science Foundation of China for the financial support(Project No.:20072026).
文摘A novel type of chiral molecular clefts consisting of a rigid deoxycholic acid methyl ester backbone and chiral unsymmetrically disubstituted urea side chain have been designed and synthesized. All these new receptors 3a^c and the corresponding key intermediates 1a^c and 2a^c are new compounds, their structures were confirmed by 1HNMR, IR, MS spectra and elemental analysis. These molecular clefts showed binding ability for halide anions.
文摘Human orofacial clefts (OFCs) are congenital anomalies that result from the breakdown of normal mechanisms that regulate the formation of the human face. They could be syndromic or non-syndromic, with a global incidence of 1:700 per live births. Environmental and genetic factors are thought to play various roles in the aetiology of OFCs. This study seeks to establish the diversity, distribution and pattern of inheritance of OFCs as well as environmental and other risk factors associated with OFCs in a Ghanaian population. A family-based, descriptive cross-sectional study that employed an interview-based survey questionnaire was used to obtain information from 467 families with history of OFCs. We employed chi-square statistics to analyse the data and used graphs to interpret the data. All previously reported subphenotypes of OFCs were observed by the present study. Clinically, about 12% of clefts in the study population were syndromic. The most common syndromic forms observed were Pierre Robin Sequence, cleft-with-club foot abnormalities and Van der Woude Syndrome. Only about 5% of clefts in the study cohort were familial. The study also established that lower level of education of parents, poverty, late antenatal care and dietary folate deficiency are major environmental factors associated with clefts in the Ghanaian population. In conclusion, OFCs are non-randomly distributed in Ghana and folate deficiency could likely be a source of genetic mutations and “epimutations” that cause OFCs, since folate is essential for DNA methylation, replication and repair as well as histone modification.
文摘<strong>Introduction: </strong>The management of nasolabial-palatal clefts in precarious environments is one of the topics most addressed by many humanitarian missions, especially in Africa and Asia. The aim of our study was to propose a humanitarian and not expensive care to the patients presenting with facial clefts during the fairgrounds in disadvantaged areas. <strong>Patients and</strong> <strong>Method:</strong> We carried out a prospective study on 32 patients who were operated with very limited means during the mobile clinics inside Togo during the year 2013. These patients were followed over a period of one year after their surgery. Included in our series were native patients with facial clefts, who had no means of managing their condition, and who therefore needed humanitarian support. We have reported the clinical history of some patients to illustrate our results. <strong>Results:</strong> Our study included 32 children, including 15 boys and 17 girls, with a sex ratio of around 1. The average age of patients was 5 years, with extremes of 6 months and 13 years. We performed 13 clefts (including 12 unilateral clefts and 1 bilateral cleft), 17 clefts palate (including 12 unilateral clefts and 5 bilateral clefts), and 2 velar clefts. We described the clinical history of a few patients in this humanitarian setting and showed the surgical results obtained.
文摘Purpose: The evaluation of the patients with clefts;the number, type, distribution by gender, etiological factors in Aegean region in Turkey between the years 2000 to 2011. Material and Method: The patients with clefts who referred to Ege University from different cities were evaluated. The number of the clefts, the type of the clefts, and the causative etiological factors which were known, were recorded for each year separately, from 2000 to 2011. At the same time, the distribution of the gender was made for each year. Chi-square test is used for the statistical evaluation. Results: According to the results of the study, the numbers of the patients with clefts were increased day by day. Totally 741 (49.6% female, 50.4% male) patients with clefts were identified. Unilateral complete cleft lip and palate appeared in the left side was seen more in males (23.8%), while seconder palate cleft was seen more in females (16.7%). Drugs, which were used in the first trimester of the pregnancy, were the most seen etiological factors for the clefts (42.5%), while genetic was 23.3% only. Conclusion: The prevention for one of the mostly seen congenital anomaly;cleft lip and palate is still unknown. For this reason, the determination of the newborn babies with cleft lip and palate has an important role in order to give these patients more effective treatment.
文摘A rapid, safe, and efficient method for the synthesis of novel molecular clefts based on deoxycholic acid was reported. Seven new molecular clefts have been synthesized in good yields （89-98%）. This method proved to be extremely simple and highly efficient. The structures of these receptors were confirmed by 1H NMR, IR, MS spectra and elemental analysis. 2007 Zhi Gang Zhao. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
基金supported by the Japan Society for the Promotion of Science(JSPS)KAKENHI(grant numbers 25670774,15K11004)to NF
文摘Oral clefts, the most frequent congenital birth defects in humans, are multifactorial disorders caused by genetic and environmental factors. Epidemiological studies point to different etiologies underlying the oral cleft phenotypes, cleft lip(CL),CL and/or palate(CL/P) and cleft palate(CP). More than 350 genes have syndromic and/or nonsyndromic oral cleft associations in humans. Although genes related to genetic disorders associated with oral cleft phenotypes are known, a gap between detecting these associations and interpretation of their biological importance has remained. Here, using a gene ontology analysis approach, we grouped these candidate genes on the basis of different functional categories to gain insight into the genetic etiology of oral clefts. We identified different genetic profiles and found correlations between the functions of gene products and oral cleft phenotypes. Our results indicate inherent differences in the genetic etiologies that underlie oral cleft phenotypes and support epidemiological evidence that genes associated with CL/P are both developmentally and genetically different from CP only, incomplete CP, and submucous CP. The epidemiological differences among cleft phenotypes may reflect differences in the underlying genetic causes. Understanding the different causative etiologies of oral clefts is important as it may lead to improvements in diagnosis, counseling, and prevention.
文摘Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of environmental and genetic factors. This paper provides a review of recent progress in defining the genetic causes of NSCLP. Methods: A literature review was conducted on the Medline data by searching for the following keywords: genes, non-syndromic cleft lip-palate, and genetics of clefts lip-palates, until January 2018. Results: Various genes are identified in different population and country, with the study using case parent’s trio. The aim of this study contributes to review relative gene which has been identify in non-syndromic cleft lip and palate, and to help to have a better understanding of the inheritance pattern of this pathology and the prevention of genetic disease. Conclusion: Although three major genes have been confirmed, the genetic research is necessary to provide an understanding of the pathophysiology of the clefts lip-palates.
文摘Background: The Ghana Expanded Programme on Immunisation recommends that children receive Bacillus Calmette-Guerin (BCG) and Oral Polio Vaccine (OPV) at birth;three doses of Penta vaccine and OPV at 6, 10 and 14 weeks of age;and measles vaccine at 9 months of age. Aim/Objective: To evaluate the immunisation status of children born with orofacial clefts who visited the KATH multidisciplinary Cleft clinic. Methodology/Statistics: The study was a descriptive study with a cross-sectional design. The methodology consisted of in-person interviews of mothers of children born with cleft lip and palate reporting at KATH Cleft clinic. Interview guides were used for mothers who could not read. Mothers who were literate and as such could answer the questions directly were given questionnaires to fill. Result: It was reported that of the 83 children included, 47 (57%) had been fully vaccinated and on time, 24 (29%) had been fully vaccinated but delayed and 12 (14%) had not been vaccinated at all. Children with isolated cleft palate and macrostomia were fully vaccinated on time (77.3% and 100%, respectively) as compared to those with combined cleft lip and palate (43.3%) and isolated cleft lip (50.0%). The majority (77%) of the mothers who either had not vaccinated their children or had delayed in vaccinating them attributed stigmatisation as the main cause. Most of the mothers (95%) had knowledge of immunisation. About two-thirds of the mothers (65%) agreed that establishing an immunisation centre at the cleft clinic is the best way to improve immunisation rate among children with orofacial clefts. Conclusion: The study showed that the percentage of children with orofacial cleft who visited the KATH Cleft Clinic and were vaccinated on time was above the national average. Cleft palates were more vaccinated and on time than cleft lips. According to the children’s mothers, lack of timely vaccination was mainly due to the stigma associated with clefts in their societies.
文摘Background: In developing countries, charity cleft surgical mission is always operated by sporadic surgical teams without systematic follow up and quality assurance. In the past few decades, many mission projects have been held regularly in China. The purpose of this audit was a retrospective analysis of a 9-year cleft lip and palate charity project operated in a tertiary hospital in China Shenzhen Area to evaluate perioperative and postoperative complications. Nevertheless, understanding the risk profile is essential for establishing a sustainable in-house cleft service in Shenzhen. Methods: A detailed analysis of hospital centralized record in the The University of Hong Kong-Shenzhen Hospital (HKUSZH) was reviewed since the first charity project held in 2015. The parameters of this audit were focused on perioperative complications including anesthesia related problems, early postoperative complications in patients who underwent primary or secondary cleft surgeries. A total of 430 consecutive admitted cases of 311 non-syndromic cleft lip & palate patients were enrolled into the charity project from June 2015 to July 2024. The main anesthesia related complications that occurred during general anesthesia were respiratory tract problems, while intraoperative complication was excessive bleeding, so as wound local infection and reaction were the main early postoperative complications. Results: In our 9-year clinical audit of 430 cleft lip and palate charity surgeries in Shenzhen, we observed no mortalities and a anesthesia-related complication rate of 1.16%. Specific intraoperative complications included excessive bleeding, while early postoperative issues were dominated by wound infections. The fistula rate of 18.7% post palate repair and the average hospital stay of 3.71 days complete the profile of our surgical outcomes. These data underscore the project’s efficacy and offer a reference for international cleft missions aiming for safe and efficient surgical care. Conclusions: This study provides a thorough data review of the complications in the past 9 years charity missions for cleft lip and palate surgery in a well-structured hospital infrastructure and logistic support by local surgical team. There were no perioperative or postoperative death during the study period and the overall short-term complication rate was low. Therefore, it could be a reference model for other international cleft mission in developing country for a safe and efficient service in future.
基金funded by grants from the National Natural Science Foundation of China(grant numbers 82170912 and 82370910)the Beijing Stomatological Hospital,Capital Medical University Young Scientist Program(No.YSP202404).
文摘Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection.A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring.However,the precise relationship remains unclear.In this study,the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P.gingivalis injected intravenously and orally into pregnant mice.We investigated an obvious increasing CP(12.5%)in sonicated P.gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium.Then glycolysis and H4K12 lactylation(H4K12la)were detected to elevate in both mouse embryonic palatal mesenchyme(MEPM)cells and macrophages under P.gingivalis exposure which further promoted the transcription of metallopeptidase domain17(ADAM17),subsequently mediated the shedding of transforming growth factor-beta receptor 1(TGFBR1)in MEPM cells and mer tyrosine kinase(MerTK)in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate,eventually caused abnormalities in palate fusion and ossification.The abnormal efferocytosis also led to a predominance of M1 macrophages,which indirectly inhibited palatal osteogenesis via extracellular vesicles.Furthermore,pharmacological ADAM17 inhibition could ameliorate the abnormality of P.gingivalis-induced abnormal palate development.Therefore,our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
文摘Cleft palate is a common congenital malformation of the maxillofacial region,and its postoperative speech disorders(such as hypernasality,nasal emission,and articulation errors)can significantly impact patients’communication abilities and psychological well-being.Traditional speech-language therapy faces challenges such as insufficient personalization of training methods,limited scenarios,and low patient compliance,making it inadequate for long-term rehabilitation needs.The innovative intervention model of a mobile interactive platform combined with games and picture books,through immersive experiences,instant feedback,and engaging designs,holds promise for enhancing patient participation and overall treatment outcomes.Therefore,this paper provides a comprehensive review from five perspectives:the pathological mechanisms and treatment needs of cleft palate speech disorders,the advantages of games and picture books as carriers in cleft palate speech therapy,the technological implementation of mobile interactive platforms,clinical application effects,and current challenges and limitations.The aim is to offer valuable insights for clinical practice and technological development in cleft palate speech rehabilitation.
文摘Background: Reconstruction of Nasal Tip Columella (NTC) subunits is one of the most challenging aspects in functional aesthetic rhinoplasty. Moreover, racial variation for Asian nose rhinoplasty could even demand sophistication of tip and columella strut graft infrastructure enhancement. Various autogenous graft options such as 6th costal cartilage, septal cartilage and conchal cartilage are very commonly considered whilst the 10th costal cartilage is scarcely reported. Objective and Method: The purpose of this manuscript is to illustrate the detailed operative steps to harvest the 10th costal cartilage for infrastructural grafting at NTC subunits by a case illustration. The pros and cons of different cartilage options will be discussed, particularly its application in cleft nose rhinoplasty in Chinese patient. We have adopted the 10th rib as the key option for NTC reconstruction in 11 cases of Chinese cleft secondary rhinoplasty since 2019 and have achieved good and stable results without complications. Conclusion: The 10th costal cartilage is one of the best options in Nasal Tip Columella subunits reconstruction, particularly in complex cleft nose or failure revision aesthetic rhinoplasty cases, due to its safety of harvesting, and the sufficient quality and quantity of grafting materials it provides for simultaneous adjunctive augmentation purpose.
文摘Objective To observe the clinical efficacy of fire needling and bloodletting at cleft points for acute gouty arthritis, and to explore its functional mechanism. Methods Thirty-five patients with acute gouty arthritis were enrolled into this study, and fire needling and bloodletting with 10 mL/ time were applied at cleft points of corresponding meridians and collaterals at the affected side. The treatment was conducted for once every other day, and treatment for three consecutive times was needed. Serum uric acid （UA） and pain score were tested in patients before treatment and on the 6th day after treatment, follow-up visit for 3 months was performed in patients who stopped treatment, and recurrence rate was calculated. Results Budzyuski 6-point behavioral rating scale was applied to score pain. T-test was conducted on mean and standard deviation of pain score before treatment （4.09 ＋ 0.82） and after treatment （1.14 ＋ 1.33）, showing that the difference was significant （P〈0.05）; t-test was also conducted on mean and standard deviation of serum UA before treatment [（555.34 ＋ 53.09） pmol/L] and after treatment [（414.23 ＋ 67.04） pmol/L], showing that the difference was significant （P〈0.05）; among the 35 patients with acute gouty arthritis, 14 patients were cured （40.0%）, improvement was found in 19 patients （54.3%）, and effectiveness was found in 33 patients （94.3%）. Based on follow-up visit for 3 months in 33 patients with efficacy, recurrence was found in 3 patients （9.1%）. Conclusion Fire needling and bloodletting at cleft points is an effective method in treatment of acute gouty arthritis with significant analgesic effect, efficacy of reducing serum UA, high cure rate and low recurrence rate, which is worth of being generalized clinically.
文摘Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and palate develop in a very characteristic way. For ultrasonographers involved in screening these patients it is crucial to have a thorough understanding of the embryology of the face. This could help them to make a more accurate diagnosis and save time during the ultrasound. Subsequently, the current postnatal classification will be discussed to facilitate the communication with the CP teams.
