In an attempt to generate g.A746G substitution in the BMPR-IB gene,we unexpectedly obtained BMPR-IB homozygous knockout piglets(BMPR-IB^(-/-))and heterogeneous knockout piglets with one copy of the A746G mutation(BMPR...In an attempt to generate g.A746G substitution in the BMPR-IB gene,we unexpectedly obtained BMPR-IB homozygous knockout piglets(BMPR-IB^(-/-))and heterogeneous knockout piglets with one copy of the A746G mutation(BMPR-IB-/746G)via CRISPR/Cas9 editing.Polymerase chain reaction(PCR)and sequencing revealed complex genomic rearrangements in the target region.All BMPR-IBdisrupted piglets showed an inability to stand and walk normally.Both BMPR-IB^(-/-)and BMPR-IB-/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms(ulna,radius)and disordered carpal,metacarpal,and phalangeal bones in the forelimbs.The piglets displayed more severe deformities in the hindlimbs by visual inspection,including fibular hemimelia,enlarged tarsal bone,and disordered toe joint bones.Limb deformities were more profound in BMPR-IB^(-/-)piglets than in the BMPR-IB-/746G piglets.Proteomic analysis identified 139 differentially expressed proteins(DEPs)in the hindlimb fibula of BMPR-IB-/746G piglets compared to the wild-type(WT)controls.Most DEPs are involved in skeletal or embryonic development and/or the TGF-βpathway and tumor progression.Gene Ontology(GO)and protein domain enrichment analysis suggested alterations in these processes.Of the top 50 DEPs,a large proportion,e.g.,C1QA,MYO1H,SRSF1,P3H1,GJA1,TCOF1,RBM10,SPP2,MMP13,and PHAX,were significantly associated with skeletal development.Our study provides novel findings on the role of BMPR-IB in mammalian limb development.展开更多
Congenital musculoskeletal and limb deformities(CMLD)seriously affect the physical and mental health of patients,and pose great challenges to healthcare systems worldwide.We explored the specific situation and changes...Congenital musculoskeletal and limb deformities(CMLD)seriously affect the physical and mental health of patients,and pose great challenges to healthcare systems worldwide.We explored the specific situation and changes of incidence,prevalence,disability-adjusted life years rates,and mortality of CMLD in under-5 children from 1990 to 2021 in different groups,including different regions,periods,genders and sociodemographic indices(SDI),through corresponding analytical models.Overall,the global disease burden of CMLD in under-5 children has decreased from 1990 to 2021.The disease burden of CMLD in under-5 children varied significantly among different regions and countries,and there was a strong correlation between the corresponding burden of disease and the level of SDI.In addition,cross-country inequality analysis showed that while absolute inequalities in the disease burden of CMLD in under-5 children have improved,relative inequalities have worsened.It is essential to reduce the global health impact of CMLD by implementing targeted interventions to improve health care in underdeveloped areas.展开更多
BACKGROUND We aimed to translate and culturally adapt the LIMB-Q Kids questionnaire for use in the Netherlands.The LIMB-Q Kids is a patient-reported outcome measure designed to assess functional,psychosocial,and aesth...BACKGROUND We aimed to translate and culturally adapt the LIMB-Q Kids questionnaire for use in the Netherlands.The LIMB-Q Kids is a patient-reported outcome measure designed to assess functional,psychosocial,and aesthetic aspects of living with a limb difference in paediatric populations.AIM To investigate the feasibility of a questionnaire in the Netherlands,which was translated into Dutch after having already been successfully translated and validated in several other languages.METHODS The translation and adaptation process followed best practice guidelines,including forward and backward translation,expert panel review,and cognitive debriefing interviews with patients.The interviews focused on the clarity and comprehensibility of the instructions,response options,and questionnaire items.RESULTS The rigorous process resulted in a linguistically and conceptually equivalent Dutch version of the LIMB-Q Kids questionnaire.While some challenges were encountered,no major difficulties were reported.The constructs and cultural relevance were found to be relatable to the Dutch context.Minor adjustments were made based on patient feedback,such as clarifying questions and modifying translations for technical terms.CONCLUSION We demonstrated the successful translation and cultural adaptation of the LIMB-Q Kids questionnaire for use in the Netherlands.By following best practices,the researchers have developed a version that is conceptually and linguistically equivalent to the original English version.The availability of this Dutch version will facilitate the assessment of outcomes in paediatric populations with limb differences,and potentially enable cross-cultural comparisons.展开更多
The purpose of this study was to report the use and assess the effects of extracorporeal shockwave therapy (ESWT) for the treatment of carpal joint valgus deformities (CJVDs) in young foals. Only foals with CJVDs grea...The purpose of this study was to report the use and assess the effects of extracorporeal shockwave therapy (ESWT) for the treatment of carpal joint valgus deformities (CJVDs) in young foals. Only foals with CJVDs greater than 5° were included in the study. Foals were assigned to 3 treatment groups based on their degree of CJVD measured during the initial evaluation: valgus deformity (VD) of 5° to 8.9° (Group 1), VD of 9° to 11.9° (Group 2) and VD greater than or equal to 12° (Group 3). ESWT was applied on the convex side of the angular deformity immediately following the initial radiographic evaluation. Foals were subsequently evaluated clinically and radiologically followed by treatment every 10 days until resolution of the VD, with resolution defined as a deviation less than 5 degrees. Each treatment group received specific exercise, hoof trimming and hoof/shoe extension recommendations. Sixty-four (64) foals were included in the study;ages ranged from 8 to 60 days old at inclusion in the study with a mean age of 26.7 days. Of the 28 foals included in Group 1, 10 had bilateral CJVD. There were 21 in Group 2, and 15 in Group 3. Treatment success was defined as a VD angle less than 5°, and was reached in all foals in Groups 1 and 2. Five (5) foals in Group 3 completed the study with a VD angle of 5° to 6.7° at the last radiographic assessment. No major complications were observed during the study. In conclusion, ESWT in conjunction with controlled exercise, hoof trimming and hoof/shoe extensions corrected severe CJVDs in young foals. The use of ESWT eliminates possible negative side effects of general anesthesia and surgical techniques to treat VDs. Future studies should include a control population, more severe cases, other types of angular limb deformities, and older foals.展开更多
BACKGROUND Triphalangeal thumb-polysyndactyly syndrome(TPT-PS)is a rare type of congenital limb deformity,and most studies focus on the genetics.Case reports of the sonographic characteristics of TPT-PS during pregnan...BACKGROUND Triphalangeal thumb-polysyndactyly syndrome(TPT-PS)is a rare type of congenital limb deformity,and most studies focus on the genetics.Case reports of the sonographic characteristics of TPT-PS during pregnancy are rare.CASE SUMMARY A 30-year-old woman(G3P1)who had pregnancies with TPT-PS fetuses is presented.The possibility of TPT-PS was shown by ultrasound performed at the 19th wk of pregnancy,featuring hands with six metacarpals,an extra digit at the 5th finger side,and an abnormally widened thumb.Whole-exome sequencing was subsequently conducted.The results showed that exons 1-17 of the LMBR1 gene had a heterozygous duplication,with a length of approximately 253 kb.CONCLUSION We suggest prenatal ultrasound examination combined with genetic testing to diagnose TPT-PS accurately and to help clinicians and patients make decisions.展开更多
Coronal plane deformity around the knee,also known as genu varum or genu valgum,is a common finding in clinical practice for pediatricians and orthopedists.These deformities can be physiological or pathological.If unt...Coronal plane deformity around the knee,also known as genu varum or genu valgum,is a common finding in clinical practice for pediatricians and orthopedists.These deformities can be physiological or pathological.If untreated,pathological deformities can lead to abnormal joint loading and a consequent risk of premature osteoarthritis.The aim of this review is to provide a framework for the diagnosis and management of genu varum and genu valgum in skeletally immature patients.展开更多
基金supported by the National Natural Science Foundation of China(31560304)National Key Research Programs of China(2016ZX08006-003)。
文摘In an attempt to generate g.A746G substitution in the BMPR-IB gene,we unexpectedly obtained BMPR-IB homozygous knockout piglets(BMPR-IB^(-/-))and heterogeneous knockout piglets with one copy of the A746G mutation(BMPR-IB-/746G)via CRISPR/Cas9 editing.Polymerase chain reaction(PCR)and sequencing revealed complex genomic rearrangements in the target region.All BMPR-IBdisrupted piglets showed an inability to stand and walk normally.Both BMPR-IB^(-/-)and BMPR-IB-/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms(ulna,radius)and disordered carpal,metacarpal,and phalangeal bones in the forelimbs.The piglets displayed more severe deformities in the hindlimbs by visual inspection,including fibular hemimelia,enlarged tarsal bone,and disordered toe joint bones.Limb deformities were more profound in BMPR-IB^(-/-)piglets than in the BMPR-IB-/746G piglets.Proteomic analysis identified 139 differentially expressed proteins(DEPs)in the hindlimb fibula of BMPR-IB-/746G piglets compared to the wild-type(WT)controls.Most DEPs are involved in skeletal or embryonic development and/or the TGF-βpathway and tumor progression.Gene Ontology(GO)and protein domain enrichment analysis suggested alterations in these processes.Of the top 50 DEPs,a large proportion,e.g.,C1QA,MYO1H,SRSF1,P3H1,GJA1,TCOF1,RBM10,SPP2,MMP13,and PHAX,were significantly associated with skeletal development.Our study provides novel findings on the role of BMPR-IB in mammalian limb development.
基金supported by the Scientific Research Projects of Colleges and Universities in Gansu Province(No.2023CYZC-03).
文摘Congenital musculoskeletal and limb deformities(CMLD)seriously affect the physical and mental health of patients,and pose great challenges to healthcare systems worldwide.We explored the specific situation and changes of incidence,prevalence,disability-adjusted life years rates,and mortality of CMLD in under-5 children from 1990 to 2021 in different groups,including different regions,periods,genders and sociodemographic indices(SDI),through corresponding analytical models.Overall,the global disease burden of CMLD in under-5 children has decreased from 1990 to 2021.The disease burden of CMLD in under-5 children varied significantly among different regions and countries,and there was a strong correlation between the corresponding burden of disease and the level of SDI.In addition,cross-country inequality analysis showed that while absolute inequalities in the disease burden of CMLD in under-5 children have improved,relative inequalities have worsened.It is essential to reduce the global health impact of CMLD by implementing targeted interventions to improve health care in underdeveloped areas.
文摘BACKGROUND We aimed to translate and culturally adapt the LIMB-Q Kids questionnaire for use in the Netherlands.The LIMB-Q Kids is a patient-reported outcome measure designed to assess functional,psychosocial,and aesthetic aspects of living with a limb difference in paediatric populations.AIM To investigate the feasibility of a questionnaire in the Netherlands,which was translated into Dutch after having already been successfully translated and validated in several other languages.METHODS The translation and adaptation process followed best practice guidelines,including forward and backward translation,expert panel review,and cognitive debriefing interviews with patients.The interviews focused on the clarity and comprehensibility of the instructions,response options,and questionnaire items.RESULTS The rigorous process resulted in a linguistically and conceptually equivalent Dutch version of the LIMB-Q Kids questionnaire.While some challenges were encountered,no major difficulties were reported.The constructs and cultural relevance were found to be relatable to the Dutch context.Minor adjustments were made based on patient feedback,such as clarifying questions and modifying translations for technical terms.CONCLUSION We demonstrated the successful translation and cultural adaptation of the LIMB-Q Kids questionnaire for use in the Netherlands.By following best practices,the researchers have developed a version that is conceptually and linguistically equivalent to the original English version.The availability of this Dutch version will facilitate the assessment of outcomes in paediatric populations with limb differences,and potentially enable cross-cultural comparisons.
文摘The purpose of this study was to report the use and assess the effects of extracorporeal shockwave therapy (ESWT) for the treatment of carpal joint valgus deformities (CJVDs) in young foals. Only foals with CJVDs greater than 5° were included in the study. Foals were assigned to 3 treatment groups based on their degree of CJVD measured during the initial evaluation: valgus deformity (VD) of 5° to 8.9° (Group 1), VD of 9° to 11.9° (Group 2) and VD greater than or equal to 12° (Group 3). ESWT was applied on the convex side of the angular deformity immediately following the initial radiographic evaluation. Foals were subsequently evaluated clinically and radiologically followed by treatment every 10 days until resolution of the VD, with resolution defined as a deviation less than 5 degrees. Each treatment group received specific exercise, hoof trimming and hoof/shoe extension recommendations. Sixty-four (64) foals were included in the study;ages ranged from 8 to 60 days old at inclusion in the study with a mean age of 26.7 days. Of the 28 foals included in Group 1, 10 had bilateral CJVD. There were 21 in Group 2, and 15 in Group 3. Treatment success was defined as a VD angle less than 5°, and was reached in all foals in Groups 1 and 2. Five (5) foals in Group 3 completed the study with a VD angle of 5° to 6.7° at the last radiographic assessment. No major complications were observed during the study. In conclusion, ESWT in conjunction with controlled exercise, hoof trimming and hoof/shoe extensions corrected severe CJVDs in young foals. The use of ESWT eliminates possible negative side effects of general anesthesia and surgical techniques to treat VDs. Future studies should include a control population, more severe cases, other types of angular limb deformities, and older foals.
基金Supported by Fund of the Research Project of Collaborative Innovation Center for Maternal and Infant Health Service Application Technology,No.XJM1802.
文摘BACKGROUND Triphalangeal thumb-polysyndactyly syndrome(TPT-PS)is a rare type of congenital limb deformity,and most studies focus on the genetics.Case reports of the sonographic characteristics of TPT-PS during pregnancy are rare.CASE SUMMARY A 30-year-old woman(G3P1)who had pregnancies with TPT-PS fetuses is presented.The possibility of TPT-PS was shown by ultrasound performed at the 19th wk of pregnancy,featuring hands with six metacarpals,an extra digit at the 5th finger side,and an abnormally widened thumb.Whole-exome sequencing was subsequently conducted.The results showed that exons 1-17 of the LMBR1 gene had a heterozygous duplication,with a length of approximately 253 kb.CONCLUSION We suggest prenatal ultrasound examination combined with genetic testing to diagnose TPT-PS accurately and to help clinicians and patients make decisions.
文摘Coronal plane deformity around the knee,also known as genu varum or genu valgum,is a common finding in clinical practice for pediatricians and orthopedists.These deformities can be physiological or pathological.If untreated,pathological deformities can lead to abnormal joint loading and a consequent risk of premature osteoarthritis.The aim of this review is to provide a framework for the diagnosis and management of genu varum and genu valgum in skeletally immature patients.
