Brucellosis is one of the most widespread zoonoses globally, which poses serious threats to both global public health and development of animal husbandry. Conventional brucellosis control measures suffer problems of surveillance coordination, regional joint prevention, and policy implementation, which are insufficient to address the challenges of ecological risks and crosshost transmission. The One Health approach allocates interdisciplinary and intersectoral collaborations to achieve systemic health of humans, animals, and environments, which provides new insights into brucellosis control programmes. This review describes the pathogenic biological characteristics, global epidemiological landscape, and transmission ecology of brucellosis, evaluates the main limitations of current control strategies, summarizes the experiences from successful One Health practices across countries at different stages of development, and proposes the brucellosis control strategy based on the One Health concept with adaptations to the current epidemiology of brucellosis in China, so as to provide the theoretical evidence and practical framework for the national brucellosis control programmes in China, thereby facilitating the effective control and the ultimate elimination of brucellosis.

OBJECTIVE: To explore the protective effects and underlying mechanisms of H ₂S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells. METHODS: Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2 (Nrf2), and cystathionine β-synthase (CBS) expression were determined using western blotting or real-time PCR. Sulforaphane (SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression. RESULTS: GYY4137 (an H ₂S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uranium-decreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes. Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability. CONCLUSION H ₂S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H ₂S axis. Simultaneously, the Nrf2-controlled CBS/H ₂S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycle-regulating mode through which H ₂S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
NF-E2-Related Factor 2/genetics* ; Animals ; Hydrogen Sulfide/pharmacology* ; Rats ; Signal Transduction/drug effects* ; Lipid Peroxidation/drug effects* ; Cell Line ; Uranium/toxicity* ; Antioxidant Response Elements ; Kidney/metabolism* ; Oxidative Stress/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects*

Objective:To explore the intervention effects of the skill training for parents with autism child (STPAC) on toddlers with autism spectrum disorder (ASD).Methods:A multicenter non-randomized concurrent controlled study design was conducted. Thirty children with ASD aged 15-30 months, first diagnosed at the Children′s Hospital of Fudan University, the First Hospital of Jilin University, and Chengdu Women′s and Children′s Central Hospital from 2019 to 2020, were enrolled in the STPAC group. Thirty children with ASD who visited the same hospitals during the same period but refused the STPAC intervention were selected as the control group. The STPAC group received an 8-week intervention (3 h/week) followed by quarterly follow-ups for 1 year, while the control group voluntarily chose community-based routine interventions. The Griffiths development scales-Chinese (GDS-C) was used to assess the developmental levels, and the communication and symbolic behavior scales developmental profile infant-toddler checklist (CSBS-DP-ITC) was completed by the primary caregivers to evaluate social, language and symbolic behavior. The independent samples t-tests or Mann-Whitney U tests, etc.was used for inter-group comparison. The paired t-tests or Wilcoxon signed-rank tests, etc. was used for inter-group pre-post intervention comparison. Results:The STPAC group included 30 children (22 males and 8 females, aged (23.9±2.2) months), and the control group included 30 children (20 males and 10 females, aged (24.2±2.6) months). Before the intervention, there were no statistically differences in GDS-C development quotient (DQ) and CSBS-DP-ITC scores between groups (all P>0.05). After 1-year intervention, GDS-C DQ in personal-social, hearing-language, hand-eye coordination, performance domains of STPAC group and GDS-C DQ in personal-social, hearing-language domains of control group were all increased (all P<0.01). After 1-year intervention, CSBS-DP-ITC scores of both groups were all improved in socia, language, symbolic behavior, and total scores (all P<0.001). GDS-C DQ changes before and after 1 year of intervention in hearing-language, hand-eye coordination, performance domains of the STPAC group were all higher the those of control group (34(15, 48 vs. 10(-4, 39), 11±20 vs. -1±19, 23±25 vs. 8±22, all P<0.05). CSBS-DP-ITC scores changes before and after 1 year of intervention in social and total scores of the STPAC group were both higher the those of control group (10(5, 30) vs. 3(1, 7), 26±17 vs. 11±8, both P<0.001). Conclusion:Compared with the community routine interventions, the STPAC better improves the language, hand-eye coordination, visual-spatial, social communication, and play skills in ASD toddlers.

Objective:To construct a key item checklist for the Mini-HTA report specification,providing scientific guidance for drafting each section of Mini-HTA research reports,enhancing their standardization,scientific rigor,and completeness,thereby improving the efficiency and quality of health decision-making.Methods:Based on preliminary literature review and qualitative systematic review,a pool of problem items for the Mini-HTA report specification was formed.Delphi questionnaires were distributed,and the Delphi technique was employed through two rounds of expert consultation to optimize and select key items.Results:Through two rounds of Delphi expert consultation,the initial Mini-HTA report specification item checklist was screened,integrated,and supplemented.A finalized key item checklist was constructed,comprising 8 first-level items(Title,Abstract,Introduction,Methods,Results,Discussion,Conclusion,and Other Relevant Information)and 48 second-level items.Conclusion:The constructed key item checklist for the Mini-HTA report specification provides scientific guidance for drafting Mini-HTA research reports.It helps enhance the standardization and transparency of the assessment process and the reliability of results,thereby optimizing the efficiency and quality of health decision-making.

OBJECTIVE: To investigate the clinical and genetic characteristics of a Chinese pedigree affected with Neurodevelopmental disorder with absent language and variable seizures (NEDALVS) due to variant of WASF1 gene, and to review the literature on NEDALVS associated with WASF1 gene variants. METHODS: A 4-year-and-8-month-old boy with NEDALVS diagnosed at Linyi People's Hospital in July 2024 due to "discovering language development delay for more than 2 years" and his family members were selected as the study subjects. Clinical data of the family members were collected. Peripheral venous blood samples were collected from family members. Whole-exome sequencing (WES) was performed, and candidate variants were verified, by Sanger sequencing. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG). Using the MUpro website, SWISS-MODEL, PyMOL, Clustal X, PolyPhen-2, and Mutation Taster software, bioinformatics analysis of protein three-dimensional structure modeling for gene mutations, cross-species conservation of mutant amino acids, and pathogenicity prediction of mutation sites. Relevant literature was retrieved from databases such as CNKI, Wanfang Data Knowledge Service Platform, and PubMed, and the clinical phenotypes and genotypes of patients with WASF1 gene mutations reported in the literature were summarized and analyzed. This study was approved by the Medical Ethics Committee of Linyi People's Hospital (Ethics No.: YX200303). RESULTS: The proband, a 4-year and 8-month-old male, mainly presented with delayed language and motor development, accompanied by autistic behaviors; the proband's younger brother was 2 years and 7 months old at the time of consultation, mainly presented with delayed language and motor development, accompanied by short stature; the proband's mother mainly presents with limited language expression and poor interpersonal interaction; the proband's maternal grandmother mainly presents with soliloquizing?behavior. The results of WES showed that the proband carried a heterozygous mutation c.214C>T (p.Arg72Cys) in the WASF1 gene, and this site has not been recorded in the database. Sanger sequencing confirmed that the proband's younger brother, mother, and maternal grandmother had harbored the same variant. Based on the guidelines from the ACMG, this variant was rated as likely pathogenic (PM2_Supporting+PP1+PP3+PP4). Through SWISS-MODEL homology modeling and PyMOL structure visualization analysis, it was further confirmed that this variant can lead to a decrease in protein stability. Amino acid sequence conservation analysis of the WASF1 protein using Clustal X software suggested that the c.214C>T (p.Arg72Cys) variant has caused replacement of a highly conserved amino acid. According to the results of PolyPhen-2 and Mutation Taster, the p.Arg72Cys variant was predicted to be a hazardous. By following the retrieval strategy set in this study, a total of 5 research articles regarding to patients with NEDALVS caused by WASF1 gene mutations were retrieved, which involved 15 patients. Combining the proband and their family members discovered in this study, there were a total of 19 NEDALVS patients. The main clinical features included: motor developmental delay (100%, 17/17), language/intellectual developmental delay (100%, 17/17), epilepsy (64.7%, 11/17), autistic behavior (76.5%, 13/17), hypotonia (70.6%, 12/17), abnormal electroencephalogram (64.7%, 11/17), and short stature (17.6%, 3/17). All 19 patients had heterozygous mutations, with 8 mutation sites. Missense mutations were the most common, accounting for 84.2% (16/19). CONCLUSION A pathogenic variant of the WASF1 gene was identified in a pedigree affected with NEDALVS. Discovery of the novel variant has, expanded the mutational spectrum of the WASF1 gene.
Child, Preschool ; Female ; Humans ; Infant ; Male ; China ; Exome Sequencing ; Mutation ; Neurodevelopmental Disorders/genetics* ; Pedigree ; Seizures/genetics* ; East Asian People/genetics*

OBJECTIVE: To investigate the clinical and genetic characteristics of a family with Vissers-Bodmer Syndrome (VIBOS) and to review the relevant literature on VIBOS caused by CNOT1 gene variants. METHODS: A child diagnosed with VIBOS due to "growth retardation for over 6 years" at the Linyi People's Hospital on March 1, 2024 and her family members were selected as the study subjects. Clinical data of the family were collected. Peripheral venous blood samples were collected from the family members. Whole-exome sequencing (WES) was performed on the proband's peripheral blood, and Sanger sequencing was used for verification of the candidate variant in the family. Pathogenicity of the candidate variant was classified according to the "Standards and Guidelines for the Interpretation of Sequence Variants" established by the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). Bioinformatics analysis, including pathogenicity prediction using Mutation Taster, three-dimensional protein structure modeling using SWISS-MODEL, and functional impact assessment using PyMOL, was performed. Relevant literature on VIBOS patients due to variants of the CNOT1 gene was retrieved from databases such as CNKI, Wanfang Data, and PubMed. The clinical phenotypes and genotypes of the patients were summarized. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: YX200303). RESULTS: The proband, a 6-year-and-7-month-old female, presented with short stature, distinctive facial features (esotropia, hypertelorism, prominent nasolabial folds), webbed neck, clinodactyly, and intellectual disability. WES revealed that she has carried a heterozygous c.736delG (p.V246*) variant of the CNOT1 gene, which was unreported previously. The proband's father exhibited borderline intellectual function but no short stature or distinctive facial features. Sanger sequencing confirmed that he has carried the same heterozygous variant. According to the ACMG guidelines, this genetic variant was predicted as "likely pathogenic" (PVS1+PM2_Supporting). The c.736delG (p.V246*) variant was predicted to have a deleterious effect by Mutation Taster. Subsequent homology modeling using SWISS-MODEL, coupled with structural visualization and comparison using PyMOL, confirmed that it may cause premature termination of translation and produce a truncated protein. Literature search has retrieved five articles on VIBOS due to CNOT1 gene variants, which included 45 cases. Together with the proband and her father, the common clinical features among these 47 patients included distinctive facial features (83.0%, 39/47), speech delay (70.2%, 33/47), motor delay (70.2%, 33/47), intellectual disability (59.6%, 28/47), and short stature (48.9%, 23/47). In terms of the types of the variants, missense variants were the most common (47.4%, 18/38), followed by frameshift variants (21.0%, 8/38). The variant sites have mainly located in exons 7, 25, and 31. No significant genotype-phenotype correlation was noted. CONCLUSION The c.736delG (p.V246*) frameshift variant of the CNOT1 gene is likely the genetic etiology of VIBOS in this proband. The clinical manifestations of the proband were more severe than in her fathers, which suggested phenotypic variability associated with this variant. This study has provided new evidence for the understanding of the genetic basis of VIBOS.
Child ; Female ; Humans ; Male ; Exome Sequencing ; Intellectual Disability/genetics* ; Mutation ; Pedigree ; Transcription Factors/genetics* ; East Asian People/genetics*

Objective:To explore the intervention effects of the skill training for parents with autism child (STPAC) on toddlers with autism spectrum disorder (ASD).Methods:A multicenter non-randomized concurrent controlled study design was conducted. Thirty children with ASD aged 15-30 months, first diagnosed at the Children′s Hospital of Fudan University, the First Hospital of Jilin University, and Chengdu Women′s and Children′s Central Hospital from 2019 to 2020, were enrolled in the STPAC group. Thirty children with ASD who visited the same hospitals during the same period but refused the STPAC intervention were selected as the control group. The STPAC group received an 8-week intervention (3 h/week) followed by quarterly follow-ups for 1 year, while the control group voluntarily chose community-based routine interventions. The Griffiths development scales-Chinese (GDS-C) was used to assess the developmental levels, and the communication and symbolic behavior scales developmental profile infant-toddler checklist (CSBS-DP-ITC) was completed by the primary caregivers to evaluate social, language and symbolic behavior. The independent samples t-tests or Mann-Whitney U tests, etc.was used for inter-group comparison. The paired t-tests or Wilcoxon signed-rank tests, etc. was used for inter-group pre-post intervention comparison. Results:The STPAC group included 30 children (22 males and 8 females, aged (23.9±2.2) months), and the control group included 30 children (20 males and 10 females, aged (24.2±2.6) months). Before the intervention, there were no statistically differences in GDS-C development quotient (DQ) and CSBS-DP-ITC scores between groups (all P>0.05). After 1-year intervention, GDS-C DQ in personal-social, hearing-language, hand-eye coordination, performance domains of STPAC group and GDS-C DQ in personal-social, hearing-language domains of control group were all increased (all P<0.01). After 1-year intervention, CSBS-DP-ITC scores of both groups were all improved in socia, language, symbolic behavior, and total scores (all P<0.001). GDS-C DQ changes before and after 1 year of intervention in hearing-language, hand-eye coordination, performance domains of the STPAC group were all higher the those of control group (34(15, 48 vs. 10(-4, 39), 11±20 vs. -1±19, 23±25 vs. 8±22, all P<0.05). CSBS-DP-ITC scores changes before and after 1 year of intervention in social and total scores of the STPAC group were both higher the those of control group (10(5, 30) vs. 3(1, 7), 26±17 vs. 11±8, both P<0.001). Conclusion:Compared with the community routine interventions, the STPAC better improves the language, hand-eye coordination, visual-spatial, social communication, and play skills in ASD toddlers.

Objective To explore the relative positioning of the superior orbital fissure and internal carotid artery through CT three-dimensional reconstruction,and to provide anatomical references for safe dissection during surgeries involving the orbital apex from a radiological perspective.Methods Totally 64 cases(128 sides)of head and neck CT angiography were analyzed and Mimics 21.0 software was employed for three-dimensional reconstruction.Measurements were taken on the three-dimensional models,including the distance from the inner boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery.Distances were also measured from the lower boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery.Additionally,measurements were taken from the upper boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery.Patient demographic data such as gender,age,and sphenoid sinus aeration were recorded,and anatomical variations were analyzed in correlation with the measured result.Results Distances were measured as follows,d1(6.32±1.98)mm,d2(7.13±2.66)mm,and d3(9.88±2.29)mm from the inner boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery,respectively.Distances were also measured as d4(11.93±2.17)mm,d5(10.39±2.36)mm,and d6(16.18±2.28)mm from the lower boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery,respectively.Distances from the upper boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery were measured as d7(7.91±2.55)mm,d8(9.63±2.99)mm,and d9(10.09±2.72)mm,respectively.The relative distance between the superior orbital fissure and the cavernous segment of the internal carotid artery was significantly greater in males than in females.In patients under 20 years of age,d7-d9 were significantly smaller than in patients over 20 years old,with statistically significant differences.There was a correlation between the type of sphenoid sinus aeration and the main measured parameters d1-d6,while the degree of sphenoid sinus aeration and the presence of the superior orbital fissure were not significantly correlated with the main measured parameters.Conclusion Three-dimensional reconstruction based on CT angiography provides a better assessment of the distance between the superior orbital fissure and internal carotid artery.This method holds clinical reference value for orbital apex surgeries and ensures a safe dissection distance.