Objective To explore the applicability of four risk assessment methods in evaluating occupational health risks associated with low-level benzene homologues exposure in key work sites within the automobile manufacturing industry. Methods The work sites (paint mixing and spray painting) with exposure to benzene homologues among six automobile manufacturing enterprises in Guangdong Province were selected as the study subjects using the judgmental sampling method. Qualitative risk assessment, exposure index method, non-carcinogenic risk assessment, and the International Council on Mining and Metals risk rating method were independently applied to evaluate the occupational health risks of benzene homologues at these work sites. Accuracy, consistency, and correlation of the four methods were compared. Results The air levels of benzene, toluene, xylene, and ethylbenzene in work sites of paint mixing and spray painting across all six enterprises met national occupational health standards. The median ratios of occupational exposure limits for benzene and toluene in spray painting site were higher than those in paint mixing site (0.017 vs 0.010, P<0.05). Using this ratio as a reference for evaluating method accuracy, the non-carcinogenic risk assessment method could distinguish paint mixing site from spray painting site in terms of risk level (P<0.05), whereas the other three methods could not (both P>0.05). The result of consistency testing revealed that the Kappa coefficients between the four methods ranged from -0.13-0.26, indicating poor consistency. The result of Spearman correlation analysis showed that the non-carcinogenic risk assessment and exposure index methods had higher correlation with occupational exposure limits ratios (Spearman correlation coefficients were 0.501 and 0.656, respectively, all P<0.05). Conclusion Occupational health risk assessment can serve as a supplementary tool to evaluate the hazard level of key work sites in the automobile manufacturing industry. Non-carcinogenic risk assessment shows higher accuracy.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective To analyze the status of occupational disease hazards in Shantou City for 2019 to 2022 and propose corresponding management measures. Methods Technical reports on various occupational-disease-specific activities in Shantou City from 2019 to 2022 were collected and the data were comprehensively analyzed. Results Among the 3 066 enterprises surveyed in the 2020 occupational disease hazard investigation in Shantou City, occupational hazards were reported in 2 982 enterprises (accounting for 97.3%), with 2 955 being small and micro enterprises, accounted for 99.1%(2 955/2 982). The exposure rate of occupational hazards was 58.7% (42 894/73 054) among workers in the surveyed enterprises, with dust and noise exposure rates of 59.7% and 77.8%, respectively. The reported rate of occupational disease hazard projects by employers, regular detection rate of workplace occupational hazards, detection rate of occupational medical examination among workers, and occupational health training rate of key responsible personnel and occupational health management staff were 8.4%, 1.4%, 2.4%, and 4.3%, respectively. The results of occupational hazards monitoring of workplace in key industries from 2019 to 2022 showed that noise had the highest rate of exceeding national standards workplace, followed by silica dust, accounting for 34.2% and 13.8%, with the on-site exceedance rate of 32.2% and 10.0%, respectively. From 2019 to 2022, 31 suspected occupational disease cases were identified in key occupational disease monitoring, including 27 suspected cases of occupational pneumoconiosis and four suspected cases of occupational noise-induced deafness. Conclusion The workers in Shantou City have a high exposure rate to occupational hazards, and the occupational health management level of employers remains low, with noise and silica dust being the most severe occupational hazards. It is essential to improve technical support and service system development for occupational disease prevention and treatment, strengthen supervision and management in key industries and positions, explore occupational health assistance mechanisms for small and micro enterprises, and enforce employers' responsibility in occupational disease prevention to protect workers' occupational health and safety.

Objective:To investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype.Methods:This case series study was performed on pediatric patients who were referred to the Children′s Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples.Results:A total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121). Conclusions:Patients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.

Objective:To explore the effects of genotypes of one-carbon metabolism (OCM)-related enzyme single nucleotide polymorphisms (SNPs) sites and anti-epileptic drugs on OCM metabolite levels in epileptic patients, and to screen valproic acid (VPA) teratogenic susceptibility genes.Methods:Three hundred and seventy-two epileptic patients, admitted to our hospital from January 2019 to December 2020, were enrolled in the study; patients taking VPA, levetiracetam (LEV), lamotrigine (LTG) or oxcarbazepine (OXC) for more than 6 months without attack during regular medication were classified as VPA group ( n=95), LEV group ( n=61), LTG group ( n=57) and OXC group ( n=70); firstly diagnosed epileptic patients who had never taken antiepileptic drugs or had not taken antiepileptic drugs in the previous 6 months were assigned into blank control group ( n=89). Plasma folic acid (FA), vitamin B12 (VitB 12) and homocysteine (Hcy) levels were determined by automatic chemiluminescence immunoassay, and genotypes of OCM-related enzyme SNPs sites were detected by Sequenom iPLEX. Results:(1) As compared with LEV group and blank control group, VPA group had significantly decreased FA level and significantly increased Hcy level ( P<0.05). (2) Patients with DNA methyltransferase (DNMT) 3a rs12987326(-178G>A) GA type had significantly higher Hcy level than those with GG type ( P<0.05); patients with DNMT1 rs2288350(82G>C) GC type had significantly higher Hcy level than those with GG type ( P<0.05); patients with DNMT1 rs75616428 (55850G>C) GC type had significantly lower VitB 12 level than those with GG type ( P<0.05). Patients with DNMT1 rs1863771(128G>A) GA+AA type had significantly higher FA level than those with GG type, patients with folate receptor 2 rs2298444(59T>C) CT+CC type had significantly higher Hcy level than those with TT type, patients with 5,10-methylenetetrahydrofolate reductase rs1801131(1298A>C) AC+CC type had significantly higher Hcy level than those with AA type, and patients with DNMT3a rs6722613(2327C>T) CT+TT type had significantly lower VitB 12 level than those with CC type ( P<0.05). Conclusions:Decreased FA and increased Hcy levels can be noted in epileptic patients who used VPA; some gene variations in SNPs of OCM also affect the OCM metabolite levels in epileptic patients. Epileptic patients during pregnancy should avoid using VPA or detecting SNPs genotypes before medication to reduce the incidence of fetal malformation.

Objective:To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder.Methods:Children with language delay/disorder who were admitted to the Department of Health Care, Children′s Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared.Results:A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ2=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ2=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups( t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions:Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.

Objective:To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder.Methods:Children with language delay/disorder who were admitted to the Department of Health Care, Children′s Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared.Results:A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ2=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ2=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups( t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions:Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.

OBJECTIVETo observe the clinical effect differences between infraoccipital needle-knife and massage for cervical vertigo.

METHODSA total of 366 patients with cervical vertigo were randomly assigned into a needle-knife group (186 cases) and a massage group (180 cases). With cases dropping excluded, 183 cases in the needle-knife group and 176 cases in the massage group were included. Needle-knife was used at Fengchi (GB 20), infraoccipitalpoint, etc. in the needle-knife group. The treatment was given for one course, once three days, 5 times as one course. The traditional massage was applied in the massage group for one course, including systematic stroking, kneading, and the application of pressure and plucking, etc., once every two days and 7 times as one course. The dizziness handicap inventory (DHI) score was observed before and after treatment, as well as 3, 6, and 12 months after treatment. The effects were also evaluated.

RESULTSThe total effective rate was 92.3% (169/183) in the needle-knife group, which was better than 85.2% (150/176) in the massage group (<0.05). Compared with those before treatment, the DHI scores at all the observation time points after treatment were improved in the two groups (all<0.05), with better improvements after treatment as well as 3 and 6 months after treatment in the needle-knife group (all<0.05). There was no significant difference in the improvement of DHI scores between the two groups 12 months after treatment (>0.05). The recurrence rate was 10.3% (12/117) in the needle-knife group, and it was 10.7% (11/103) in the massage group 12 months after treatment (>0.05).

CONCLUSIONSInfraoccipital needle-knife achieves apparent effect for cervical vertigo, which is superior to massage in short period.

[Objective] To refer a geographical distribution rule of alpha-L-fucosidase (AFU) reference values for the health adults in China via exploring its spatial distribution trend and its correlation with geographical factors.[Methods] A total of 6564 samples of AFU reference values from 66 administrative units in the years 2004-2015 were collected,male and female of which were 3701 cases (56.4％) and 2863 cases (46.3％).A research concerning AFU reference values in whole country were calculated using methods of information content and ridge regression.[Results] AFU reference values for Chinese healthy adults were influenced by geographical factors and presented autocorrelation,and it showed eastern and northern areas were highery than western and southern areas.[Conclusions] AFU reference values have a spatial variation and the regional disparities should be considered in practice.