BackgroundDementia seriously affects the quality of life and lifespan of elderly people， with Alzheimer's disease （AD） being the most common type of dementia. Previous studies have suggested that gout may reduce the risk of developing AD， but the causal relationship between the two still requires further research. ObjectiveTo investigate the potential causal relationship between gout and AD through a two-sample Mendelian randomization （MR） analysis， so as to provide references for the prevention and treatment of AD. MethodsData from Genome-Wide Association Studies （GWAS） extracted in 2024 were analyzed， using pooled data on gout （6 810 cases in the case group and 477 788 cases in the control group） published by UK Biobank in 2021 as the exposure variable， and data on AD （3 899 cases in the case group and 214 893 cases in the control group） published by FinnGen in the same year as the outcome variable. The inverse-variance weighted， MR-Egger regression， weighted median estimation， simple model and weighted model were used to analyze the potential causal relationship between gout and AD. Pleiotropic effects were assessed using MR-Egger regression. Heterogeneity assessment was conducted using Cochran's Q test. The leave-one-out analysis was carried out for sensitivity analysis. And a funnel plot was drawn to detect potential publication bias. ResultsThe inverse-variance weighted analysis demonstrated a negative causal relationship between gout and AD （OR=0.004， 95% CI： 0~0.700， P<0.05）. The plot resembled a symmetrical inversed funnel， indicating the absence of publication bias. No heterogeneity was detected by Cochran's Q test. The MR-Egger regression indicated no significant horizontal pleiotropy. Concerning the reverse directions， no significant associations between AD and gout were noted. ConclusionThere is a negative causal relationship between gout and AD， with gout potentially reducing the risk of developing AD. ［Funded by The Third Batch of Social Welfare and Basic Research Projects （Medical and Health） of Zhongshan City in 2022 （number， 2022B3017）］

Background Environmental metal exposure is closely associated with the onset and progression of mild cognitive impairment (MCI) in the elderly. Effectively identifying hazardous metal exposure and assessing their interaction effects have significant public health implications. Objective To explore the relationship between urinary single metal and metal mixture exposure and MCI in elderly compound residents. Methods This study included 391 elderly individuals aged 60 and above from residential compounds in Zhongshan City, Guangdong Province. Concentrations of iron (Fe), copper (Cu), selenium (Se), arsenic (As), cadmium (Cd), manganese (Mn), chromium (Cr), nickel (Ni), vanadium (V), cobalt (Co), antimony (Sb), thallium (Tl), zinc (Zn), calcium (Ca), and magnesium (Mg) in urine were measured using inductively coupled plasma mass spectrometry. Cognitive function in the elderly was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Logistic regression was used to explore the relationship between single metal exposure level and MCI. LASSO regression and multi-metal logistic regression models were used to identify key metal ions associated with MCI. Bayesian kernel machine regression (BKMR) was employed to analyze the relationship between key metal ion mixtures and MCI, as well as the interactions between metals. Age, gender, education level, occupation, and body mass index were adjusted as covariates. Results A total of 78 among the 391 elderly individuals surveyed (19.94%) were diagnosed with MCI (MCI group), and the other 313 individuals were controls. The levels of Se, Cd, Mn, and As in the urine of the MCI group were significantly higher than those in the control group (P < 0.05). In the single-metal model, after adjusting for covariates and using the first quartile (Q₁) of each metal concentration as the reference, the OR for MCI in the elderly in the Q₄ group of Se was 2.190 (95%CI: 1.017, 4.716); for Cd, the OR was 2.345 (95%CI: 1.041, 5.283) in the Q₃ group and 2.371 (95%CI: 1.043, 5.393) in the Q₄ group; for Mn, the OR was 2.355 (95%CI: 1.038, 5.344) in the Q₂ group; for As, the OR was 3.377 (95%CI: 1.442, 7.908) in the Q₃ group and 2.886 (95%CI: 1.227, 6.788) in the Q₄ group; for Sb, the OR was 2.779 (95%CI: 1.234, 6.257) in the Q₂ group. When urinary metal concentrations were ln-transformed and included as continuous variables in the single-metal model, Cd concentration was positively correlated with MCI (OR=1.377; 95%CI: 1.008, 1.882; P=0.044). Cd, Se, Mg, Ca, Mn, As, Cr, Co, Tl, and Sb were selected by the LASSO regression model and included in the multi-metal model. In the multi-metal model, compared with Q₁, the OR for MCI in the elderly was 0.395 (95%CI: 0.164, 0.953) in the Q₂ group of Co and 0.390(95%CI: 0.167，0.911) in the Q₃ group of Co; for Mn, the OR in the Q₂ group was 2.636 (95%CI: 1.053, 6.596); for Sb, the OR in the Q₂ group was 2.640 (95%CI: 1.047, 6.658). As continuous variables, Mg (OR=0.472; 95%CI: 0.248, 0.899; P=0.022) and Co (OR=0.857; 95%CI: 0.737, 0.996; P=0.044) concentrations were negatively correlated with MCI. The BKMR mixture analysis suggested that Mg and Co exhibited a synergistic negative correlation with MCI, while Mn and Sb exhibited a synergistic positive correlation with MCI. Mg and Co attenuated the positive correlation of Mn and Sb with MCI, whereas Mn weakened the protective effects of Mg and Co. Conclusion Elevated levels of Se, Cd, As, Mn, and Sb in urine may increase the risk of MCI in the elderly, while Mg and Co have protective effects. Potential synergistic or antagonistic interactions may be found among Mn, Sb, Mg, and Co, which should not be overlooked in terms of their impact on the cognitive function of the elderly.

Objective: To investigate the influencing factors of depressive symptoms and to construct and verify the prediction model of depressive symptoms in middle school students, so as to provide risk assessment tools for effectively screening depressive symptom. Methods: Physical examination and questionnaire survey were conducted among middle school students in one city in Guangdong Province from September to October in 2021 ( n =2 376) and from September to October in 2022 ( n =4 344) by a multistage cluster sampling method, and a nomographic prediction model of depressive symptoms in middle school student was constructed. The questionnaire survey was conducted using the student health status and influencing factors questionnaire (secondary school version) and the Center for Epidemiological Studies Depression Scale (CES-D) to measure the lifestyle and depressive symptom of middle school students. Results: The detection rate of depressive symptoms in 2021 was 23.3%. Multivariate Logistic regression analysis showed that irregular breakfast ( OR =2.64), school bullying ( OR =4.28), being beaten by parents ( OR =2.86), using mobile devices for a long time ( OR =1.08) and sitting for a long time ( OR =1.05) were positively related to depressive symptoms in middle school students ( P <0.05). Long sleep duration ( OR =0.78) and outdoor activity durations of 1-<2, 2-<3 and ≥3 h/d (compared with <1 h/d, OR =0.63, 0.61, 0.49) were negatively related to depressive symptoms in middle school students ( P < 0.05 ). Multivariate Logistic regression analysis showed that 7 statistically signifucant predictive factors constructed a nomogram, and the AUC of the nomogram was 0.77, which had been verified internally and externally with good differentiation and reliability. Conclusions The nomogram prediction model of depressive symptoms provides a convenient and effective risk assessment tool for depressive symptoms among middle school students. The life behavior, diet behavior and injury behavior of middle school students play an important role in the formation of depressive symptoms. It should pay attention to the impact of the behavioral factors on the mental health of middle school students.

Objective:To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals.Methods:In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 μmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) .Results:Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 μmol/L PQ-treated BV2 cells compared with the 0 μmol/L, and the differences were statistically significant ( P<0.05) . Conclusion:Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.

Objective:To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals.Methods:In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 μmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) .Results:Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 μmol/L PQ-treated BV2 cells compared with the 0 μmol/L, and the differences were statistically significant ( P<0.05) . Conclusion:Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.

Objective:To explore the surgical intervention strategy for metastatic cervical lymph nodes surrounding the carotid artery in head and neck squamous cell carcinoma.Methods:A total of 62 patients with advanced head and neck tumors and carotid wrap by disease treated in Department of Otorhinolaryngology and Head and Neck Surgery, the Affiliated BenQ Hospital of Nanjing Medical University between June 2019 and December 2023 were reviewed, of whom 9 patients presented with metastatic squamous cell carcinoma in cervical lymph nodes of unknown primary or with no recurrence of primary lesion and all the 9 patients were males, aged from 48 to 79 years old, with≤level 2 of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS). Radiographically common carotid artery (CCA) and/or internal carotid artery (ICA) were surrounded by≥270° with tumor. All the 9 patients received implantation of covered stent in carotid artery and radical resection of metastatic cervical lymph nodes. The success rate, complications, surgery-related complications, local recurrence rate, quality of life (QOL) and overall survival (OS) were analyzed. The QOL of patients was compared by paired rank sum test, and P<0.05 indicated statistically significant difference. The OS was analyzed by Kaplan-Meier. Results:The success rate of stent implantation was 100%, with no implantation-related complications. R0 resection was performed in 8 cases and R1 resection in 1 case. The QOL of patients after surgery was improved, and the improvements in "pain", "mood" and "anxiety" were statistically significant( Z values were -2.236, -2.460 and -2.200, respectively, and all P values were<0.05). Follow-up was 1-18 months, with a median of 7 months, and 1 case was lost to follow-up. Local recurrence occurred in 3 patients with an incidence of 37.5% (3/8). OS was 59.9% at 12 months after surgery. Conclusion:Implantation of covered stent in carotid artery combined with radical resection is an effective method for the treatment of cervical lymph node metastasis.

OBJECTIVE: To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). METHODS: Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES). RESULTS: All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant. CONCLUSION The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.
Child ; Humans ; Acyl-CoA Dehydrogenase/genetics* ; Carnitine ; Genetic Testing ; Lipid Metabolism, Inborn Errors/genetics* ; Neonatal Screening

OBJECTIVE: To explore the clinical features and genetic basis of a child with Galactosemia. METHODS: A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing. RESULTS: Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR). CONCLUSION Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.
Child ; Female ; Humans ; Galactosemias/genetics* ; Genetic Testing ; Health Status ; Methionine ; Muscle Hypotonia ; Mutation

Objective:To investigate the value of three-dimensional (3D) CT in diagnosing cricoarytenoid dislocation.Methods:From January 2021 to December 2021, 31 patients with unilateral cricoarytenoid dislocation who had been treated by reduction forceps at the Affiliated BenQ Hospital of Nanjing Medical University were collected retrospectively, and their voice recovered or improved significantly after therapy. The preoperative CT images were reconstructed by volume rendering (VR). The dislocated side (left and right), type of dislocation (total dislocation and subluxation), and dislocation direction (anterior, posterior, internal and external dislocation) of cricoarytenoid dislocation were observed. According to arytenoid articular surface of cricoid cartilage exposed completely or not (caused by arytenoid displacement), they were divided into complete dislocation and subluxation. According to the direction of arytenoid displacement and the part of arytenoid articular surface of cricoid cartilage exposed, they were divided into anterior, posterior, internal and external dislocation. According to the shape of the vocal cords on laryngoscope, anterior and posterior dislocation of each case was judged, and then compared with that of CT.Results:On VR images, there were 28 cases of cricoarytenoid subluxation (90.3%, 28/31) and 3 cases of complete dislocation (9.7%, 3/31). Left cricoarytenoid dislocation was 26 cases (83.9%, 26/31) and right cricoarytenoid dislocation was 5 cases (16.1%, 5/31). Posterior dislocation was 28 cases (90.3%, 28/31) and anterior dislocation was 3 cases (9.7%, 3/31). There were 23 cases of internal dislocation (74.2%, 23/31), 2 cases of external dislocation (6.4%, 2/31), and 6 cases without obvious internal and external dislocation (19.4%, 6/31). Three cases of complete dislocation were left posterior internal dislocation.There were 24 cases of left posterior dislocation (77.4%, 24/31), 4 cases of right posterior dislocation (12.9%, 4/31), 2 cases of left anterior dislocation (6.4%, 2/31) and 1 case of right anterior dislocation (3.2%, 1/31). On laryngoscope, there were 19 cases of posterior dislocation (61.3%, 19/31), 9 cases of anterior dislocation (29.0%, 9/31), 3 cases were difficult to assess (9.7%, 3/31) because of aryepiglottic fold covering. Sixteen cases (55.2%, 16/28) were consistent with 3D CT, and 12 cases (42.8%, 12/28) were inconsistent.Conclusion:The 3D CT is a reliable method to evaluate cricoarytenoid dislocation, which can show dislocated side, type and direction of cricoarytenoid dislocation clearly.

Background Paraquat (PQ) is one of the most widely used herbicides in the world and a risk factor for Parkinson's disease (PD), but the mechanisms underlying PD are poorly understood. Single-cell RNA sequencing (scRNA-seq) technology can study cellular heterogeneity at genetic level, providing insights into the pathogenesis of PQ-induced PD. Objective To analyze the brain cell grouping of PQ-infected mice and the biological processes involved in the subpopulation of PD-like changes cells by scRNA-seq, and to provide clues for revealing potential mechanisms of PQ-induced PD-like changes in mouse brains. Methods Six male 6-week-old C57BL/6 mice were randomly divided into a control group and an experimental group, three mice in each group, and were intraperitoneally injected with 0 (saline) and 10.0 mg·kg⁻¹ PD respectively, once every two days, for 10 consecutive injections for modeling. After infection, mouse brains were taken and scRNA-seq was performed. Cell segmentation was performed according to gene expression characteristics of different cell types, PD-related cell subsets were screened by bioinformatics tools, and gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), protein interaction network analysis, and transcription factor prediction were performed on their characteristic genes. Finally, GO and KEGG analyses were performed on the differential genes of PD-associated cell subsets between the PQ-treated group and the control group, and the biological processes in which these genes may participate were analyzed. Results The sequencing data met quality control standards, a total of 55779 cells were obtained, and all cell dimensionality reduction analysis results showed that they could be further divided into 37 clusters, including 5 major cell types. Based on the KEGG analysis of the top 20 characteristic genes of each subpopulation, the specifically expressed Cluster 33 subpopulation (dopaminergic neurons) was screened and found to be significantly associated with PD. The results of GO analysis showed that the biological function of this subpopulation mainly enriched neurotransmitter transport and regulation. The results of GSEA analysis showed that the tyrosine metabolic pathway and the ligand-receptor interaction pathway of neural activity in brain tissues were significantly enriched. The analysis of transcriptional regulatory networks showed that 39 transcription factors were expressed differently. The metabolic pathway of the dopamine neuronal subset, endocytosis, Ras-associated protein 1 (Rap1) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway were all affected by PQ exposure, according to further analysis of its effects on this subpopulation. The GO analysis showed that differential genes were involved in biological processes such as ion transport and synaptic assembly regulation, and were involved in the cellular component formation of cytoplasm and synapses. Conclusion This study has initially mapped the transcriptome of single cells in the mouse brain after PQ exposure, and screened out the specific expression of Cluster 33 subgroup (dopaminergic neurons), which is significantly correlated with PD, and its biological function changes may be one of the mechanisms of PD-like changes in the mouse brain induced by PQ.