OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

Objective:To explore the clinical characteristics and genetic etiology of a child with Osteopathia striata with cranial sclerosis (OSCS) due to variant of AMER1 gene. Methods:A child presented at the Affiliated Children′s Hospital of Zhengzhou University in July 2024 due to growth and development retardation was selected as the study subject. A retrospective study was conducted to collect the child′s clinical data. Peripheral blood samples (2 mL each) were collected from the child and her parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used for the verification of candidate variants. The pathogenicity of variant was rated according to the guidelines from American College of Medical Genetics and Genomics (ACMG). The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No.: 2024-108-001).Results:The patient, a 4-year-and-10-month-old girl, presented with global developmental delay, short stature, cleft palate, distinct facial features, and hearing impairment. WES revealed that she has harbored a heterozygous c. 790_794dup (p.Cys265Trpfs*19) variant of the AMER1 gene, which was not detected in either parent. Based on the guidelines from ACMG, the gene variant was classified as pathogenic (PVS1 + PS2 + PM2_supporting). As the result of a non-triplet base insertion in the coding region of the AMER1 gene, it has converted a codon originally encoding an amino acid into a stop codon, and led to a truncated protein, causing severe alteration and dysfunction of the protein. Conclusion:The child was diagnosed with OSCS for clinical features such as global developmental delay, short stature, cleft palate, distinctive facial features, and hearing impairment, for which the de novo heterozygous frameshift variant AMER1: c. 790_794dup (p.Cys265Trpfs*19) may be accountable. Above finding has expanded the mutational spectrum of OSCS and provided a basis for genetic counseling and prenatal diagnosis for the family.

Objective:To analyze the distribution and epidemiological characteristics of common non-bacterial pathogens in hospitalized children with acute respiratory tract infections(ARTI)from a multi-center study covering 4 regions in Fujian Province in 2023.Methods:A retrospective cohort study was conducted using medical record analysis.A total of 22 769 hospitalized children with ARTI were enrolled from January to December 2023 across seven regional pediatric medical centers in Fujian Province (covering four major geographical divisions of Fuzhou, Nanping, Sanming and Longyan; all selected hospitals were regional children′s medical centers).Using single-tube multiplex PCR with fragment analysis on a Sanger sequencing platform, the nucleic acids of 11 common non-bacterial respiratory pathogens were tested in nasopharyngeal swabs collected from 22 769 children. These pathogens included influenza A virus(FluA), influenza B virus(FluB), parainfluenza virus(PIV), respiratory syncytial virus (RSV), adenovirus (ADV), human rhinovirus (HRV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus(HMPV), Mycoplasma pneumoniae(MP), and Chlamydia (Ch). Count data were described as [ n(%)], and the chi-square test/Fisher′s exact test was used to compare the differences in rates between groups. Epidemiological features, including positive detection rates, pathogen profiles, and correlations with region, sex, age and month, were analyzed. Results:Among 22 769 children with ARTI, pathogens were detected in 16 213 cases (71.21%), including 13 340 single infections (58.59%).The detection rates of single pathogens in descending order were human rhinovirus (HRV, 12.95%), Mycoplasma pneumoniae(MP, 12.27%), respiratory syncytial virus(RSV, 11.12%), influenza A virus (Flu-A, 7.98%), parainfluenza virus(PIV, 4.66%), human metapneumovirus(HMPV, 4.60%), adenovirus(ADV, 2.70%), human bocavirus(HBoV, 0.84%), human coronavirus(HCoV, 0.82%), influenza B virus(Flu-B, 0.47%) and Chlamydia(Ch, 0.18%).Mixed infections occurred in 2 873 cases(12.62%), primarily dual infections(2 679 cases).Regional analysis revealed significant disparities:Luoyuan County Hospital (Fuzhou) exhibited the highest total detection rate(86.59%, 1 414/1 633)and mixed infection rate(23.27%, 380/1 633)(both P<0.001), with notably elevated MP (26.39%, 431/1 633);Jian′ou City Hospital(Nanping) ranked second for Flu-A(14.21%, 409/2 879), RSV(13.20%, 380/2 879) and mixed infections(17.12%, 493/2 879);Lianjiang County Hospital(Fuzhou) showed distinct prevalence of Flu-A(10.68%, 130/1 217), PIV(6.00%, 73/1 217), and HBoV(1.73%, 21/1 217); Yong′an City Hospital (Sanming) reported high MP (26.07%, 238/913) and RSV(12.38%, 113/913);Shaowu City Hospital(Nanping) was dominated by MP (18.60%, 407/2 188) and HRV(13.39%, 293/2 188); Tingzhou Hospital(Longyan) had the highest HRV (17.88%, 407/2 276) and Flu-B (0.75%, 17/2 276); and Fuzhou Children′s Hospital showed elevated ADV(3.38%, 394/11 663) and HCoV(1.08%, 126/11 663). Except for Flu-B(0.47%, 108/22 769; P=0.054) and Ch(0.18%, 40/22769; P=0.900), all pathogens and mixed infections exhibited significant regional variations ( P<0.05).Gender analysis indicated higher detection rates of HRV, RSV, Flu-A, ADV, PIV, HBoV and mixed infections in males, while MP, HMPV, Flu-B, HCoV, and Ch were more prevalent in females, with statistically significant differences for HRV and MP (both P<0.001). Age stratification showed the highest overall detection rate in the 3-<6 years group (75.48%; P<0.001): RSV and Ch peaked in infants (<1 year), HRV, PIV, ADV and HBoV in toddlers (1-<3 years), HMPV, HCoV, and mixed infections in preschool children (3-<6 years), and MP, Flu-A and Flu-B in older children (6-<18 years).Analyzing the prevalent months, the monthly prevalence trends of pathogens in various regions are similar.Seasonal trends demonstrated year-round HRV activity (peaking in spring/autumn), MP prevalence in autumn/winter, RSV surges in spring-summer (April-June) and late summer-autumn (August-October), and Flu-A predominanced in winter-spring. Conclusion:Multiplex PCR with fragment analysis demonstrated high diagnostic efficacy. The top 4 non-bacterial pathogens in Fujian Province′s ARTI-hospitalized children in 2023 were HRV, MP, RSV and Flu-A. Pathogen distribution exhibited significant regional, age and seasonal variations, emphasizing the need for targeted prevention strategies.

Objective:To summarize the clinical and genetic characteristics of patients with neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) caused by MAPK8IP3 gene variation. Methods:The clinical data and genetic testing results of 2 children with NEDBA treated in Henan Children′s Hospital from August 2019 to January 2022 were collected retrospectively. Literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed database and OMIM database (up to October 2024) with" MAPK8IP3 gene ""NEDBA ""neurodevelopmental disorders "as the search terms. The main clinical genetic characteristics of NEDBA caused by MAPK8IP3 gene variation were summarized. Results:The 2 children, a boy aged 1 year and 8 months and a girl aged 1 year and 4 months, both showed global developmental delay and the onset of the disease in infancy. The de novo heterozygous mutation c.1732C>T(p.Arg578Cys) of the MAPK8IP3 gene was detected by whole-exome sequencing. Case 1 was followed up to 3 years and 10 months old, who had severe developmental delay and was accompanied by hip subluxation and strephexopodia. Literature search retrieved 0 Chinese literature and 2 English literatures. A total of 18 patients including 2 cases reported in this study were identified as NEDBA caused by MAPK8IP3 gene variations, including 16 cases with missense mutations and 2 cases with truncation mutations. Among them, 7 patients carried c.1732C>T(p.Arg578Cys) and 5 patients carried c.3436C>T(p.Arg1146Cys). The main clinical manifestations of the 18 patients included developmental delay/intellectual disability (18 cases), poor or absent speech (11 cases), abnormal neurological examination (10 cases: 6 with spastic paraplegia, 2 with spasticity, 2 with ataxia, 1 with unstable gait), hypotonia (10 cases), skeletal malformations (10 cases: 4 with short stature, 3 with scoliosis, 1 with 5th finger clinodactyly and brachydactylky, 1 with flat-valgus feet, 1 with hip subluxation), seizures (3 cases), left hearing loss (1 case), myopic astigmatism and pseudostrabismus (1 case), abnormal brain magnetic resonance imaging (15 cases). Conclusions:Patients with NEDBA is usually characterized by global developmental delay apparent from infancy or early childhood, resulting in language and motor disorders. Additional features may include hypotonia, spasticity, skeletal malformations and abnormal brain magnetic resonance imaging. Currently, missense variations are frequent among the heterozygous MAPK8IP3 genotypes, among which c.1732C>T(p.Arg578Cys) and c.3436C>T(p.Arg1146Cys) are considered hot spot variations.

Objective To observe the clinical efficacy of Dan Qi Yishen Prescription in treating diabetic nephropathy(DN)and explore its renal protective mechanism.Methods A total of 150 patients with DN of qi-yin deficiency complicated with blood stasis syndrome who admitted to Sanya Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from October 2021 to April 2023 were divided into a control group and an observation group according to the random number table method,with 75 patients in each group.Both groups were given conventional therapies such as dietary treatment,blood glucose control,blood pressure control,lipid-lowering treatment and treatment of complications.Additionally,the control group was given intravenous injection of reduced glutathione,while the observation group was given oral use of the decoction of Dan Qi Yishen Prescription and ionic introduction of Dan Qi Yishen Prescription in renal region.Thirty days constituted one course of treatment,and both groups were treated for three courses.Before and after treatment,the scores of traditional Chinese medicine(TCM)syndrome,and the levels of renal function indicators,renal hemodynamic indicators,coagulation and fibrinolysis indicators,and vascular endothelial function indicators in the two groups were observed.Results(1)After treatment,the scores of TCM symptoms such as fatigue and weakness,palpitations and shortness of breath,dizziness and tinnitus,spontaneous sweating and night sweating,restlessness and insomnia,and thirst with preference for drinks in the two groups were decreased compared with those before treatment(P<0.01),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(2)After treatment,the levels of renal function indicators such as blood urea nitrogen(BUN),serum creatinine(SCr),collagen Ⅳ(CⅣ),and plasma laminin(LN)of patients in the two groups were improved compared with those before treatment(P<0.01),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the levels of renal hemodynamic indicators such as systolic maximum blood flow velocity(Vsmax)and diastolic minimum blood flow velocity(Vdmin)of the main renal artery(MRA)and interlobar artery(IRA)in the two groups were increased compared with those before treatment(P<0.05 or P<0.01),while the resistance index(RI)and pulsatility index(PI)of MRA and RI of IRA in the two group as well as PI of IRA in the observation group were decreased compared with those before treatment(P<0.05 or P<0.01).The increase of Vsmax and Vdmin of MRA and IRA as well as the decrease of RI and PI of MRA and IRA in the observation group was significantly superior to that in the control group(P<0.05 or P<0.01).(4)After treatment,the levels of coagulation and fibrinolysis indicators such as prothrombin time(PT),activated partial thromboplastin time(APTT),D-dimer(D-D),and fibrinogen(FIB)in the two groups were improved compared with those before treatment(P<0.01),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(5)The analysis of vascular endothelial function indicators showed that after treatment,the serum vasohibin 1(VASH-1)level in the two groups was increased compared with that before treatment(P<0.01),and the serum vascular endothelial growth factor(VEGF)and endothelin 1(ET-1)levels were decreased compared with those before treatment(P<0.01),and the increase of serum VASH-1 level as well as the decrease of serum VEGF and ET-1 levels in the observation group was significantly superior to that in the control group(P<0.01).Conclusion Dan Qi Yishen Prescription exerts good clinical efficacy in treating patients with DN of qi-yin deficiency complicated with blood stasis syndrome,and it has protective effect on renal function probably by improving the coagulation and fibrinolysis system and vascular endothelial function of the patients.

Objective : To investigate the effects of acarbose and pioglitazone on the levels of sex hormones in adult female rats ，and to explore their regulatory effects on the hypothalamic-pituitary-ovarian axis ( HPOA) and its mechanism． Methods : Adult female SD rats aged 2 months were randomly divided into 0．9% sodium chloride so- lution control group (NS) ，acarbose low (AL) ，medium (AM) and high (AH) dose groups and pioglitazone low (PL) ，medium (PM) and high (PH) dose groups．AL，AM and AH groups were given 20，40 and 60 mg / (kg · d) acarbose，and PL，PM and PH groups were given 5，10 and 15 mg / (kg · d) pioglitazone，respectively．Af- ter 28 days of intervention，serum gonadotropin (FSH，LH) and ovarian secreted hormone ( E2，P，T) were de- tected by ELISA，and the effects of acarbose and pioglitazone on HPOA were investigated by organ index analysis and histopathological observation of pituitary gland and ovary． Results : Compared with the NS group，the serum FSH in the PL，PM and PH groups decreased ( all P＜0. 01) ，the serum LH in the PL，PM and PH groups de- creased (P＜0. 05，P＜0. 01，P ＜0. 01) ，and the organ indices in the PM and PH groups decreased ( all P < 0. 01) ．HE staining of the adenohypophysis in the PL，PM and PH groups showed an increase in eosinophils，a de- crease in basophils，and an expansion and increase in the number of blood sinuses．In the PM and PH groups，HE staining of the ovaries showed that there were no significant differences in follicles at all levels，but the development was poor，the number of primordial follicles decreased，and the number of corpus luteum increased．Compared with the NS group，the serum P in the AM and AH groups decreased ( all P ＜0. 01) ，and serum E2 in AM and AH groups decreasd (all P＜0. 05) ． Conclusion Pioglitazone affects HPOA by regulating pituitary function directly． However，the effect of acarbose on HPOA may be mediated through the gut-brain axis，and has no direct correlation with the ovarian structure．

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Osteopathia striata with cranial sclerosis (OSCS) due to variant of AMER1 gene. METHODS: A child presented at the Affiliated Children's Hospital of Zhengzhou University in July 2024 due to growth and development retardation was selected as the study subject. A retrospective study was conducted to collect the child's clinical data. Peripheral blood samples (2 mL each) were collected from the child and her parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used for the verification of candidate variants. The pathogenicity of variant was rated according to the guidelines from American College of Medical Genetics and Genomics (ACMG). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No.: 2024-108-001). RESULTS: The patient, a 4-year-and-10-month-old girl, presented with global developmental delay, short stature, cleft palate, distinct facial features, and hearing impairment. WES revealed that she has harbored a heterozygous c.790_794dup (p.Cys265Trpfs*19) variant of the AMER1 gene, which was not detected in either parent. Based on the guidelines from ACMG, the gene variant was classified as pathogenic (PVS1 + PS2 + PM2_supporting). As the result of a non-triplet base insertion in the coding region of the AMER1 gene, it has converted a codon originally encoding an amino acid into a stop codon, and led to a truncated protein, causing severe alteration and dysfunction of the protein. CONCLUSION The child was diagnosed with OSCS for clinical features such as global developmental delay, short stature, cleft palate, distinctive facial features, and hearing impairment, for which the de novo heterozygous frameshift variant AMER1: c.790_794dup (p.Cys265Trpfs*19) may be accountable. Above finding has expanded the mutational spectrum of OSCS and provided a basis for genetic counseling and prenatal diagnosis for the family.
Humans ; Female ; Child, Preschool ; Osteosclerosis/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Mutation ; Exome Sequencing ; Retrospective Studies ; Tumor Suppressor Proteins

Objective:To analyze the distribution and epidemiological characteristics of common non-bacterial pathogens in hospitalized children with acute respiratory tract infections(ARTI)from a multi-center study covering 4 regions in Fujian Province in 2023.Methods:A retrospective cohort study was conducted using medical record analysis.A total of 22 769 hospitalized children with ARTI were enrolled from January to December 2023 across seven regional pediatric medical centers in Fujian Province (covering four major geographical divisions of Fuzhou, Nanping, Sanming and Longyan; all selected hospitals were regional children′s medical centers).Using single-tube multiplex PCR with fragment analysis on a Sanger sequencing platform, the nucleic acids of 11 common non-bacterial respiratory pathogens were tested in nasopharyngeal swabs collected from 22 769 children. These pathogens included influenza A virus(FluA), influenza B virus(FluB), parainfluenza virus(PIV), respiratory syncytial virus (RSV), adenovirus (ADV), human rhinovirus (HRV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus(HMPV), Mycoplasma pneumoniae(MP), and Chlamydia (Ch). Count data were described as [ n(%)], and the chi-square test/Fisher′s exact test was used to compare the differences in rates between groups. Epidemiological features, including positive detection rates, pathogen profiles, and correlations with region, sex, age and month, were analyzed. Results:Among 22 769 children with ARTI, pathogens were detected in 16 213 cases (71.21%), including 13 340 single infections (58.59%).The detection rates of single pathogens in descending order were human rhinovirus (HRV, 12.95%), Mycoplasma pneumoniae(MP, 12.27%), respiratory syncytial virus(RSV, 11.12%), influenza A virus (Flu-A, 7.98%), parainfluenza virus(PIV, 4.66%), human metapneumovirus(HMPV, 4.60%), adenovirus(ADV, 2.70%), human bocavirus(HBoV, 0.84%), human coronavirus(HCoV, 0.82%), influenza B virus(Flu-B, 0.47%) and Chlamydia(Ch, 0.18%).Mixed infections occurred in 2 873 cases(12.62%), primarily dual infections(2 679 cases).Regional analysis revealed significant disparities:Luoyuan County Hospital (Fuzhou) exhibited the highest total detection rate(86.59%, 1 414/1 633)and mixed infection rate(23.27%, 380/1 633)(both P<0.001), with notably elevated MP (26.39%, 431/1 633);Jian′ou City Hospital(Nanping) ranked second for Flu-A(14.21%, 409/2 879), RSV(13.20%, 380/2 879) and mixed infections(17.12%, 493/2 879);Lianjiang County Hospital(Fuzhou) showed distinct prevalence of Flu-A(10.68%, 130/1 217), PIV(6.00%, 73/1 217), and HBoV(1.73%, 21/1 217); Yong′an City Hospital (Sanming) reported high MP (26.07%, 238/913) and RSV(12.38%, 113/913);Shaowu City Hospital(Nanping) was dominated by MP (18.60%, 407/2 188) and HRV(13.39%, 293/2 188); Tingzhou Hospital(Longyan) had the highest HRV (17.88%, 407/2 276) and Flu-B (0.75%, 17/2 276); and Fuzhou Children′s Hospital showed elevated ADV(3.38%, 394/11 663) and HCoV(1.08%, 126/11 663). Except for Flu-B(0.47%, 108/22 769; P=0.054) and Ch(0.18%, 40/22769; P=0.900), all pathogens and mixed infections exhibited significant regional variations ( P<0.05).Gender analysis indicated higher detection rates of HRV, RSV, Flu-A, ADV, PIV, HBoV and mixed infections in males, while MP, HMPV, Flu-B, HCoV, and Ch were more prevalent in females, with statistically significant differences for HRV and MP (both P<0.001). Age stratification showed the highest overall detection rate in the 3-<6 years group (75.48%; P<0.001): RSV and Ch peaked in infants (<1 year), HRV, PIV, ADV and HBoV in toddlers (1-<3 years), HMPV, HCoV, and mixed infections in preschool children (3-<6 years), and MP, Flu-A and Flu-B in older children (6-<18 years).Analyzing the prevalent months, the monthly prevalence trends of pathogens in various regions are similar.Seasonal trends demonstrated year-round HRV activity (peaking in spring/autumn), MP prevalence in autumn/winter, RSV surges in spring-summer (April-June) and late summer-autumn (August-October), and Flu-A predominanced in winter-spring. Conclusion:Multiplex PCR with fragment analysis demonstrated high diagnostic efficacy. The top 4 non-bacterial pathogens in Fujian Province′s ARTI-hospitalized children in 2023 were HRV, MP, RSV and Flu-A. Pathogen distribution exhibited significant regional, age and seasonal variations, emphasizing the need for targeted prevention strategies.

Objective:To explore the clinical characteristics and genetic etiology of a child with Osteopathia striata with cranial sclerosis (OSCS) due to variant of AMER1 gene. Methods:A child presented at the Affiliated Children′s Hospital of Zhengzhou University in July 2024 due to growth and development retardation was selected as the study subject. A retrospective study was conducted to collect the child′s clinical data. Peripheral blood samples (2 mL each) were collected from the child and her parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used for the verification of candidate variants. The pathogenicity of variant was rated according to the guidelines from American College of Medical Genetics and Genomics (ACMG). The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No.: 2024-108-001).Results:The patient, a 4-year-and-10-month-old girl, presented with global developmental delay, short stature, cleft palate, distinct facial features, and hearing impairment. WES revealed that she has harbored a heterozygous c. 790_794dup (p.Cys265Trpfs*19) variant of the AMER1 gene, which was not detected in either parent. Based on the guidelines from ACMG, the gene variant was classified as pathogenic (PVS1 + PS2 + PM2_supporting). As the result of a non-triplet base insertion in the coding region of the AMER1 gene, it has converted a codon originally encoding an amino acid into a stop codon, and led to a truncated protein, causing severe alteration and dysfunction of the protein. Conclusion:The child was diagnosed with OSCS for clinical features such as global developmental delay, short stature, cleft palate, distinctive facial features, and hearing impairment, for which the de novo heterozygous frameshift variant AMER1: c. 790_794dup (p.Cys265Trpfs*19) may be accountable. Above finding has expanded the mutational spectrum of OSCS and provided a basis for genetic counseling and prenatal diagnosis for the family.

Objective:To summarize the clinical and genetic characteristics of patients with neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) caused by MAPK8IP3 gene variation. Methods:The clinical data and genetic testing results of 2 children with NEDBA treated in Henan Children′s Hospital from August 2019 to January 2022 were collected retrospectively. Literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed database and OMIM database (up to October 2024) with" MAPK8IP3 gene ""NEDBA ""neurodevelopmental disorders "as the search terms. The main clinical genetic characteristics of NEDBA caused by MAPK8IP3 gene variation were summarized. Results:The 2 children, a boy aged 1 year and 8 months and a girl aged 1 year and 4 months, both showed global developmental delay and the onset of the disease in infancy. The de novo heterozygous mutation c.1732C>T(p.Arg578Cys) of the MAPK8IP3 gene was detected by whole-exome sequencing. Case 1 was followed up to 3 years and 10 months old, who had severe developmental delay and was accompanied by hip subluxation and strephexopodia. Literature search retrieved 0 Chinese literature and 2 English literatures. A total of 18 patients including 2 cases reported in this study were identified as NEDBA caused by MAPK8IP3 gene variations, including 16 cases with missense mutations and 2 cases with truncation mutations. Among them, 7 patients carried c.1732C>T(p.Arg578Cys) and 5 patients carried c.3436C>T(p.Arg1146Cys). The main clinical manifestations of the 18 patients included developmental delay/intellectual disability (18 cases), poor or absent speech (11 cases), abnormal neurological examination (10 cases: 6 with spastic paraplegia, 2 with spasticity, 2 with ataxia, 1 with unstable gait), hypotonia (10 cases), skeletal malformations (10 cases: 4 with short stature, 3 with scoliosis, 1 with 5th finger clinodactyly and brachydactylky, 1 with flat-valgus feet, 1 with hip subluxation), seizures (3 cases), left hearing loss (1 case), myopic astigmatism and pseudostrabismus (1 case), abnormal brain magnetic resonance imaging (15 cases). Conclusions:Patients with NEDBA is usually characterized by global developmental delay apparent from infancy or early childhood, resulting in language and motor disorders. Additional features may include hypotonia, spasticity, skeletal malformations and abnormal brain magnetic resonance imaging. Currently, missense variations are frequent among the heterozygous MAPK8IP3 genotypes, among which c.1732C>T(p.Arg578Cys) and c.3436C>T(p.Arg1146Cys) are considered hot spot variations.