Objective To comprehensively investigate the levels of exposure and distribution characteristics of trihalomethanes (THMs) in drinking water in Guangzhou City, and evaluate the health risks of different groups of children, adolescents and adults, and to provide data and evidence for protecting human health and promoting risk control of drinking water. Methods According to the technical requirements of the ^"Standards for Drinking Water Quality Testing Methods^" (GB/T 5750-2023), the concentration of THMs, including trichloromethane (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and tribromomethane (TBM) in drinking water in Guangzhou City from 2023-2024 were detected. The health risk model recommended by USEPA was used for risk assessment．Results TCM, BDCM and DBCM were detected in the factory water and terminal water, with TCM contributing the most. There was a statistically significant difference (P<0.05) between the wet and dry seasons, and the concentration of TCM in the wet season was higher than that in the dry season. Among the multiple exposure factors, the amount of exposure through drinking water intake was much greater than that through skin absorption. The carcinogenic risk index of THMs for children, adolescents, and adults was 22.0×10^-6, 12.2×10^-6, and 11.4×10^-6, respectively, while the non-carcinogenic risk was less than 1. Conclusion The exposure risks of THMs in children, adolescents, and adults is within an acceptable range, but monitoring needs to be strengthened, with a particular focus on children.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. METHODS: A child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children's Hospital Affiliated to Zhengzhou University in March 2023 due to "inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethic No.2022-K-L025). RESULTS: The child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c.240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+PM2_Supporting+PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects. CONCLUSION The frameshift variation of TRAPPC6B gene c.240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provide basis for genetic counseling and prenatal diagnosis of this family.
Humans ; Infant ; Male ; Frameshift Mutation ; Homozygote ; Neurodevelopmental Disorders/genetics* ; Phenotype

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. METHODS: A child (proband) diagnosed with DA5D and his family members (proband's parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children's Hospital in July 2022 due to "multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate's pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants were annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children's Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands. RESULTS: The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c.1742_c.1743insT and maternal c.2314T>G, for which the father and sister were carriers of the c.1742_c.1743insT heterozygous variant and the mother was carrier of c.2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c.1742_c.1743insT variant was classified as likely pathogenic (PSV1+PM2_Supporting), and c.2314T>G was classified as uncertain (PM2_Supporting+PM3+PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c.2314T>G (p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c.2314T>G missense mutation resulted in the failure of forming 1 disulfide bond. CONCLUSION The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.
Humans ; Pedigree ; Arthrogryposis/genetics* ; Male ; Female ; Heterozygote ; Phenotype ; Mutation ; Child ; Metalloendopeptidases

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 evaluate the effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant. Methods: A total of 1 403 Omicron-infected patients admitted to 20 designated hospitals in Guangdong Province from January 1 to May 31, 2022, were selected as subjects in this study. A case-control study was conducted to collect the demographic data, underlying disease, vaccination status, last exposure date, gene sequencing of infected strains and clinical outcomes from the China Disease Prevention and Control Information System and Guangdong telemedicine platform. Pneumonia (common, severe and critical) and non-pneumonia (asymptomatic and mild) were selected as the case group and control group. The effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant was analyzed. Results: The median age [M (Q₁, Q₃)] of the subjects was 36 (27-47) years old, with males accounting for 52.25% (733 cases). The main outcome of the infection was non-pneumonia, accounting for 92.09% (1 292 cases), and the duration [M (Q₁, Q₃)] of the disease was 18 (14-22) days. There were 134 (9.55%), 39 (2.78%), 403 (28.72%), 437 (31.15%) and 390 (27.80%) cases with no or partial vaccination, within 90 days of primary vaccination, over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination, respectively. Multivariate logistic regression analysis showed that after adjusting for gender, age, underlying disease, and location of the report, compared with those with no or partial vaccination, the risk of developing pneumonia was lower in those with over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination [OR (95%CI) values were 0.52 (0.28-0.98), 0.39 (0.21-0.73) and 0.40 (0.21-0.77), respectively]. Cox proportional hazard regression model analysis showed that after adjusting for gender, age, underlying disease and location of the report, the duration of the disease was shorter in those who received booster vaccinated for more than 90 days compared with that in those who had no or partial vaccination [HR (95%CI): 1.26 (1.03-1.55)]. Conclusion: The inactivated SARS-CoV-2 vaccine affects the clinical outcomes of patients infected with the Omicron variant.
Adult ; Humans ; Male ; Middle Aged ; Case-Control Studies ; China/epidemiology* ; COVID-19/prevention & control* ; COVID-19 Vaccines ; SARS-CoV-2 ; Female

OBJECTIVE: To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). METHODS: A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. RESULTS: The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. CONCLUSION The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.
DNA Copy Number Variations ; Heterozygote ; Pedigree ; Phenotype ; RNA Splicing ; Mutation

OBJECTIVE To optimize the preparation technology of the volatile oil microcapsules of Cinnamomi Ramulus and Angelicae Sinensis Radix, characterize the microcapsules prepared after the formulation optimization and study pharmacokinetics characteristics in rats. METHODS Spray drying was used to prepare the volatile oil microcapsules of Cinnamomi Ramulus and Angelicae Sinensis Radix. The preparation process was optimized by Box-Behnken response surface method with the drug loading and encapsulation efficiency as indexes. The microcapsules were characterized by Fourier transform infrared spectroscopy(FT-IR) and scanning electron microscopy(SEM). Blood samples were collected after gastric administration at a dose of 100 mg·kg-1. HPLC method was adopted in the plasma concentration determination, and pharmacokinetics behavior in vivo was also compared. RESULTS The optimal formulation: core material-capsules material ratio was 1∶1.7, capsules material concentration was 10.25%, sodium starch octenyl succinate∶maltodextrin was 3.8∶1, high pressure homogenization pressure was 20 MPa and the inlet temperature of spray drying was 185 ℃. Under the optimized conditions, the drug loading was (18.94±1.09)% and the encapsulation rate was (96.03±2.91)%, respectively. The results of FT-IR and SEM showed that the essential oils had been successfully coated in the capsule wall material. The microcapsules were basically spherical in shape, with concave surface but no obvious cracks. The main pharmacokinetic parameters such as tmax, t1/2, CL, AUC0-t, k10,k12, and k21 of microcapsules had significant difference of the volatile oil(P<0.05 or P<0.01). Microcapsules effectively prolonged the circulation time of volatile oil in the body, promoted the absorption of drugs in the body and the oral bioavailability was enhanced to 2.62 times. CONCLUSION The model established by the Box-Behnken design-response surface method can be used to optimize the formulation of volatile oil microcapsules of Cinnamomi Ramulus and Angelicae Sinensis Radix with great prediction effect. The microcapsules prepared by the optimized process has good drug loading properties and the bioavailability of volatile oil is increased.

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

Objective:To explore the relationship between rumination and depression and suicide attempts, and the mediating effect of rumination between depression and suicide attempts in adolescents with depressive disorder.Methods:Clinical interviews and questionnaires were conducted on 331 adolescents aged 11-18 with depressive disorders.Depressive symptoms were assessed with patient health questionnaire-9 (PHQ-9). Rumination was assessed with ruminative responses scale-10 (RRS-10), and Chinese version of the sociality module of MINI5.0 was used to assess suicide.SPSS 23.0 software was applied to descriptive statistics, Chi-square test, t-test, Spearman correlation analysis and hierarchical regression analysis, and the SPSS macro program PROCESS V 3.4 was used for Bootstrap mediating effect. Results:The incidence of suicide attempts in adolescents with depressive disorder was 53.78%, which was significantly higher in girls (59.48%) than that in boys (40.40%), and the difference was significant ( χ2=10.16, P<0.01). In contrast to the non-suicide attempt group, suicide attempt group had higher scores on PHQ-9((11.08±9.26) vs (14.43±7.49), t=-3.634, P<0.01), brooding ((10.76±3.89) vs (12.44±3.87), t=-3.926, P<0.01), reflection ((10.05±3.54) vs (11.20±3.33), t=-3.044, P<0.01) and rumination total score ((20.81±6.78) vs (23.64±6.42), t=-3.898, P<0.01). Regression analysis revealed that girl ( β=0.175, t=3.228, P=0.001), depressive symptoms ( β=0.168, t=3.082, P=0.002), rumination ( β=0.138, t=2.364, P=0.019) were risk factors for suicide attempts.Rumination played a complete mediating effect between depressive symptoms and suicide attempts (effect value=0.013, 95% CI=0.003-0.027). Depression symptoms significantly and positively predicted rumination ( P<0.01), and rumination significantly and positively predicted suicide attempts ( P<0.05). Conclusion:The incidence of suicide attempts was high in adolescents with depressive disorders.Depressive symptoms affect suicide attempts mainly through rumination.Clinicians should assess the rumination of adolescents with depressive disorders.In addition, clinicians should implement concurrent psychotherapy to adjust the cognitive response and reduce rumination, in order to improve the mental health and reduce suicide attempts.