OBJECTIVES: To analyze the potential causal relationship between gut microbiota and food allergy (FA) using two-sample Mendelian randomization (MR) methods. METHODS: Data from genome-wide association studies on gut microbiota and FA were utilized. MR analysis was conducted employing inverse variance weighting, MR-Egger regression, and weighted median methods to assess the causal relationship between gut microbiota and FA. Cochrane's Q test was used to evaluate heterogeneity of instrumental variables, MR-PRESSO analysis was conducted to test for outliers and pleiotropy, and MR-Egger regression was employed to assess horizontal pleiotropy. The "leave-one-out" method was used to evaluate the impact of removing individual single nucleotide polymorphisms on the causal relationship. RESULTS: Inverse variance weighting analysis revealed that the phylum Verrucomicrobia, family Verrucomicrobiaceae, order Verrucomicrobiales, genus Ruminococcaceae UCG013, and genus Akkermansia were negatively associated with FA (P<0.05). Sensitivity analyses confirmed the reliability of the findings, indicating no heterogeneity or pleiotropy present. CONCLUSIONS There is a causal relationship between gut microbiota and FA, with Verrucomicrobia, Verrucomicrobiaceae, Verrucomicrobiales, Ruminococcaceae UCG013, and Akkermansia potentially reducing the risk of developing FA. These findings provide potential targets for the treatment and prevention of FA; however, further research is needed to explore the specific mechanisms by which the microbiota influence FA.
Humans ; Mendelian Randomization Analysis ; Gastrointestinal Microbiome ; Food Hypersensitivity/microbiology* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

OBJECTIVE: Human brucellosis is a serious public health concern in the Xilingol League, Inner Mongolia; however, the epidemic trends are unclear. METHOD: In this study, Joinpoint regression analysis and spatiotemporal analysis were applied to investigate the epidemic evolution of human brucellosis. RESULT: From 2004 to 2023, a total of 35,747 cases were reported, with an annual average of 1787.35 cases and an annual average incidence rate of 176.04/100,000. The incidence increased from 173.96/100,000 in 2004 to 500.71/100,000 in 2009 and fluctuated to 61.43/100,000 in 2023. Three epidemic join points were observed in which the disease experienced an alternative rise and fall, peaking in 2009 (APC = 21.73, P > 0.001) and 2020 (APC = 21.51, P > 0.001). The disease showed a persistent decline trend in lentitude (AAPC = -5.30, P > 0.001), suggesting challenges in disease control and a higher risk of rebound. The most cases were reported in Xilinhot City ( n = 4,777), followed by 4,391 in Sonid Left Banner, and 4,324 in Abaga Banner. Spatiotemporal analysis revealed two high clusters (CI and CII) from 2005 to 2012, the high cluster encompassing eight counties and shifting from north to south. CONCLUSION The present analysis highlights that human brucellosis has decreased significantly in the Xilingol League, but the epidemic is still severe; further implementation of a strict control program is necessary.
China/epidemiology* ; Humans ; Brucellosis/epidemiology* ; Epidemics ; Spatio-Temporal Analysis ; Incidence ; Cluster Analysis

The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of Polygonatum kingianum. The fresh rhizome of P. kingianum was used as the experimental material, and the full-length transcriptome was sequenced by PacBio Sequel platform. The final measured polymerase reads were 1 120 485, with a total of 77.73 GB of data. In NR database, 41 864 homologous sequence alignments were aligned to 5 species; 40 506 were annotated in the KOG database and classified into 26 categories based on their functionality; 69 060 GO annotated 32 functional groups divided into 3 categories: cellular components, molecular functions, and biological processes; 45 779 annotations were added to 145 metabolic pathways in the KEGG database. Among them, there are 127 identified transcripts related to polysaccharide synthesis in the glycolysis/gluconeogenesis metabolic pathway, 144 in the starch and sucrose metabolic pathway, 85 in the amino acid sugar and nucleotide sugar metabolic pathway, and 69 in the fructose and mannose metabolic pathway. In addition, 1 781 transcription factors were detected, distributed in 37 transcription factor families; 180 293 SSR loci were detected, among which single base repeats accounted for the most, accounting for 30.48% of all base repeats, and at least five base repeats, accounting for only 0.14% of single base repeats. The results of this study provide important data supporting for enriching the genomic information of P. kingianum and exploring its effective biosynthetic pathway.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Objective:To explore the interrelationship among three simplified hand and wrist bone age assessment methods and to establish corresponding bone ages for each substage in male children.Methods:This retrospective case series study included 169 left hand and wrist X-rays from 152 male children who underwent bone age assessments at the Pediatric Orthopedics and Pediatrics Departments,Beijing Jishuitan Hospital,Capital Medical University from January 2019 to December 2023. The age at the time of X-ray was (13.7±2.0) years (range:9.1 to 17.9 years). Reasons for bone age assessment included evaluating the progress of adolescent idiopathic scoliosis in 36 cases, predicting limb length discrepancies in 28 cases, and predicting the height of healthy adolescents in 88 cases. Bone age was first graded using the Chinese hand-wrist bone age assessment method. Three simplified hand and wrist bone age assessment methods were then applied:Sanders simplified skeletal maturity staging system(Sanders stage), the distal radius and ulna classification (DRU), and e thumb ossification composite index (TOCI). Somers′delta correlation test was used to analyze the relationship among the results of the three simplified methods. The bone age and standard deviation for each sub-stage were calculated, and gender differences in bone age for the same sub-stage were compared with previous study.Results:The DRU, TOCI and Sanders stages showed a strong correlation when assessing bone age in male children, with Somers′delta correlation coefficients ranging from 0.881 to 0.876 (all P<0.01). The sub-stages with the smallest standard deviations (shorter duration) in each of the three classifications can serve as a quick reference for determining precise bone age, included proximal thumb epiphysis covered, without sesamoid (12.0 years);proximal thumb epiphysis covered with sesamoid or distal radial covered (13.0 years), early capping of the thumb epiphysis, radial epiphysis medial side capping(13.5 years), all phalangeal epiphyses capping (14.0 years), distal phalangeal physes beginning to close (14.5 years), all distal phalangeal physes closed (15.0 years), middle or proximal phalangeal physes beginning to close (15.5 years), all digital epiphyses closed (16.5 years), and nearly complete distal radius fusion with a notch (17.5 years). On average, the bone ages of males were 2 years behind those of females in the same substage. Conclusions:The DRU, TOCI, and Sanders stages can be applied to male children, and it is showed good correlation between them. The subtypes with shorter duration can be used as a quick assessment method to determine the bone age.

Objective:To explore the interrelationship among three simplified hand and wrist bone age assessment methods and to establish corresponding bone ages for each substage in male children.Methods:This retrospective case series study included 169 left hand and wrist X-rays from 152 male children who underwent bone age assessments at the Pediatric Orthopedics and Pediatrics Departments,Beijing Jishuitan Hospital,Capital Medical University from January 2019 to December 2023. The age at the time of X-ray was (13.7±2.0) years (range:9.1 to 17.9 years). Reasons for bone age assessment included evaluating the progress of adolescent idiopathic scoliosis in 36 cases, predicting limb length discrepancies in 28 cases, and predicting the height of healthy adolescents in 88 cases. Bone age was first graded using the Chinese hand-wrist bone age assessment method. Three simplified hand and wrist bone age assessment methods were then applied:Sanders simplified skeletal maturity staging system(Sanders stage), the distal radius and ulna classification (DRU), and e thumb ossification composite index (TOCI). Somers′delta correlation test was used to analyze the relationship among the results of the three simplified methods. The bone age and standard deviation for each sub-stage were calculated, and gender differences in bone age for the same sub-stage were compared with previous study.Results:The DRU, TOCI and Sanders stages showed a strong correlation when assessing bone age in male children, with Somers′delta correlation coefficients ranging from 0.881 to 0.876 (all P<0.01). The sub-stages with the smallest standard deviations (shorter duration) in each of the three classifications can serve as a quick reference for determining precise bone age, included proximal thumb epiphysis covered, without sesamoid (12.0 years);proximal thumb epiphysis covered with sesamoid or distal radial covered (13.0 years), early capping of the thumb epiphysis, radial epiphysis medial side capping(13.5 years), all phalangeal epiphyses capping (14.0 years), distal phalangeal physes beginning to close (14.5 years), all distal phalangeal physes closed (15.0 years), middle or proximal phalangeal physes beginning to close (15.5 years), all digital epiphyses closed (16.5 years), and nearly complete distal radius fusion with a notch (17.5 years). On average, the bone ages of males were 2 years behind those of females in the same substage. Conclusions:The DRU, TOCI, and Sanders stages can be applied to male children, and it is showed good correlation between them. The subtypes with shorter duration can be used as a quick assessment method to determine the bone age.

Objective To explore the value of the prediction model based on diffusion weighted imaging(DWI)radiomic features and apparent diffusion coefficient(ADC)values in the assessment of p53 gene mutation status in endometrial cancer(EC).Methods The DWI data of 22 p53 wild-type and 60 p53 mutant EC patients were analyzed retrospectively.The DWI radiomic features of the primary lesions were extracted,and the ADC values were calculated.The prediction model was constructed based on support vector machine(SVM)algorithm.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the performance of the prediction model.Internal validation was conducted using Bootstrap.Results The ADC value of p53 mutant EC was significantly lower than that of p53 wild-type EC(P=0.002).When comparing the ADC value and radiomics model,the combined ADC-radiomics model demonstrated the highest diagnostic efficacy,achieving an AUC of 0.924,sensitivity of 86.67％,and specificity of 90.91％.In Bootstrap-based validation,the combined ADC-radiomics model also showed high performance with an AUC of 0.904.The calibration curve and clinical decision curve analysis(DCA)showed that the combined ADC-radiomics model not only had better agreement between predicted and actual observed values but also provided better net benefits for the patients concerned.Conclusion The combined ADC-radiomics model achieved a more efficient assessment of p53 status in EC patients.