OBJECTIVE: To explore the clinical features and genetic mutation sites of 28 patients with Congenital fibrinogen disorders (CFDs). METHODS: A total of 28 unrelated CFDs patients admitted to Wenzhou People's Hospital from June 2018 to April 2023 were enrolled into this research. A total of 2.7 mL of peripheral blood was collected from each patient for coagulation function tests, which included thrombin time (TT), fibrinogen activity (Fg:C), fibrinogen antigen (Fg:Ag), and gene detection. The Sanger sequencing method was employed to verify variations in the fibrinogen (Fg) protein-coding gene across 28 patients. Bioinformatics analyses, including harmfulness analysis, conservation analysis across different species, and spatial simulation predictions of variant proteins, were conducted byPolyPhen-2, PROVEAN, SnapGene, and Pymol softwares on the variant sites of these patients. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study received approval from the Ethics Committee of Wenzhou People's Hospital (Approval No. KY-2023-269), and informed consent was obtained from all participants before enrollment. RESULTS: The clinical and genetic characteristics of 28 patients with CFDs in this study were as follows. CLINICAL DATA: Among the 28 patients, 2 cases were diagnosed with type I CFDs, while 26 cases were diagnosed with type II CFDs. And 50.0% (14/28) of the patients exhibited no clinical manifestations, while 28.6% (8/28) presented with bleeding manifestations, and 7.1% (2/28) exhibited thrombus manifestations, 3.6% (1/28) experienced both bleeding and thrombosis. Among female patients, 13.0% (3/23) exhibited a history of habitual abortion. All patients demonstrated TT and a significant decrease in Fg:C. Sanger sequencing revealed a total of 10 types of heterozygous variations in the FGA, FGB, and FGG genes across 28 patients, distributed among 9 loci. The variation at the γ c.902G>A/c.901C>T accounted for the highest proportion (35.7%, 10/28), followed by the Bβ c.569 A>G (28.6%, 8/28). Biological informatics analysis: the Aα c.180+1G>T mutation was predicted to be highly deleterious. And the Aα c.104G>A, Bβ c.425T>G, Bβ c.586C>T, and γ c.902G>A/c.901C>T variations were also predicted to be harmful. Conservation analysis indicates that the 9 variant sites were highly conserved among homo sapiens, musculus, ovis aries, scrofa, and rattus. Spatial conformation analysis revealed that some variations lead to an increase or decrease in the number of hydrogen bonds. ACMG guideline rating analysis: Among the ten variations in the Fg protein-coding genes FGA, FGB, and FGG identified in 28 patients, 9 variations (Aα c.104G>A, Aα c.180+1G>T, Bβ c.425T>G, Bβ c.569A>G, Bβ c.586C>T, Bβ c.643G>A, γ c.901C>T, γ c.902G>A, γ c.1001A>C) were classified as pathogenic, while one variation (γ c.908C>G) was classified as likely pathogenic. CONCLUSION In this study, the majority of CFDs patients are diagnosed with type II CFDs, with 50% presenting clinical symptoms predominantly manifesting as bleeding, thrombosis, and recurrent miscarriage. The mutation hotspots are mainly located in exon 2 of FGA, exon 4 of FGB, and exon 8 of FGG.
Humans ; Female ; Male ; Afibrinogenemia/congenital* ; Fibrinogen/metabolism* ; Mutation ; Genotype ; Adult ; Child ; Adolescent ; Child, Preschool ; Infant

OBJECTIVE: To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients. METHODS: Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). RESULTS: PAH gene variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS gene variants. Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) of the variants were located in exons, with the main types being missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants have occurred in the PAH gene's catalytic center region, while 19.74% (30/152) of the variants involved non-coding sequences. The phenotypes of the 75 PAHD children were evenly distributed. The re-screened Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values (P < 0.001, P < 0.001; P = 0.004, P = 0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types have significantly affected the phenotypes (P = 0.042, P = 0.045). APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes (κ = 0.755, P < 0.001). CONCLUSION PAH gene variants were detected in most HPA children from Lianyungang area. The location and type of PAH gene variants has correlated with the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model has predicted the phenotype with high consistency with the actual phenotype.
Humans ; Phenylalanine Hydroxylase/genetics* ; Female ; Phenylketonurias/enzymology* ; Male ; Phenotype ; Genotype ; Child ; Infant ; Infant, Newborn ; Child, Preschool ; China ; Mutation ; Alleles

Objective This study aims to explore the causal relationships between 731 immune cell phenotypes and cervical cancer using a two-sample Mendelian randomization(MR)analysis.Methods Utilizing results from genome-wide association study(GWAS),inverse variance weighted(IVW),MR-Egger regression,weighted median,simple mode and weighted mode were used for MR analysis,and sensitivity analysis was used for quality control of heterogeneity and horizontal pleiotropy.Results Using IVW as the primary analytical method and ensuring consistency in the direction of results across all five MR methods,we identified five immune cell phenotypes potentially causally associated with cervical cancer.Among these,relative count of central memory CD4+T cells in all CD4+T cells(CM CD4+％CD4+)(ORIVW=0.804,95％CI:0.685-0.943,PIVW=0.0074),absolute count of naive CD8 bright T cell(Naive CD8br AC)(ORIVW=0.493,95％CI:0.359-0.676,PIVW=0.000 01)and median fluorescence intensities of CD45 on immature myeloid-derived suppressor cells(CD45 on Im MDSC)(RIVW=0.746,95％CI:0.609-0.914,PIVW=0.0048)were positively associated with cervical cancer risk,while median fluorescence intensities of IgD on IgD+CD38-unswitched memory B cell(IgD on IgD+CD38-unsw mem)(RIVW=1.393,95％CI:1.148-1.690,PIVW=0.000 78)and median fluorescence intensities of CD3 on terminally differentiated CD8 bright T cell(CD3 on TD CD8br)(ORIVW=1.267,95％CI:1.082-1.483,PIVW=0.0033)were negatively associated with cervical cancer risk.Conclusion This study identifies five immune cell phenotypes closely related to cervical cancer risk through genetic analysis,providing new insights for early prevention and the development of novel immunotherapies for cervical cancer.

Objective:To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients.Methods:Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). Results:① PAH variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS variants. ② Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) were located in exons, with the main types of variants were missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants occurred in the PAH gene catalytic center region of PAH protein, while 19.74% (30/152) of variants involved non-coding sequences. ③The phenotypes of the 75 PAHD children were evenly distributed. The rescreening Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values ( P<0.001, P<0.001; P=0.004, P=0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types significantly affect the phenotype ( P=0.042, P=0.045). ④APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes ( κ=0.755, P<0.001). Conclusion:PAH variants were detected in the most of HPA children in Lianyungang area. The location and type of PAH variants were related to the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model predicted the phenotype was highly consistent with the actual phenotype.

Objective:To analyze the prevalence of chronic diseases, the level of chronic disease prevention and control literacy and its influencing factors among middle-aged and elderly residents in Wenzhou from 2020 to 2023.Methods:Based on a cross-sectional research design, 19 528 usual residents aged 45-69 were retrospectively selected with a multi-stage stratified random sampling method from the health literacy monitoring survey in Wenzhou from 2020 to 2023. The χ2 tests and trend χ2 tests were employed to analyze chronic disease prevalence rates and health literacy possession rates across different population subgroups. Binary logistic regression models were used to identify determinants of chronic disease prevention health literacy among middle-aged and elderly residents in Wenzhou. The results were standardized using data from Wenzhou′s Seventh National Population Census. Results:The numbers of middle-aged and elderly respondents was 5 528, 4 822, 4 575 and 4 603 from 2020 to 2023, respectively, and the prevalence of self-rated chronic diseases was 39.56%, 37.33%, 41.29% and 39.00%, respectively (the standardized rate was 33.49%, 33.58%, 36.43% and 35.34%, respectively) in the each year, and the rates of chronic disease prevention and control literacy was 24.76%, 27.98%, 24.44% and 28.13%, respectively (the standardized rate was 27.95%, 30.11%, 27.57%, 29.78%, respectively). The rates of chronic disease prevention and control literacy was on an upward trend in middle-aged and elderly respondents in Wenzhou from 2020 to 2023 ( χ2trend=5.997, P=0.014). From 2020 to 2023, chronic disease prevention health literacy showed a positive educational gradient, with significantly higher levels observed among more educated populations (both P<0.05). Except for 2020, the residents with household income≥30 000 yuan had a higher chronic disease prevention and control literacy than those with household income less than 30 000 yuan (both P<0.05); in 2021 and 2022, the chronic disease prevention and control literacy in the people of 45-59 years was higher than that in the individuals of 60-69 years (both P<0.05); in 2020 and 2022, the rural residents had a higher chronic disease prevention and control literacy than the urban residents, and the rates of chronic disease prevention and control literacy of employees or retirees in government institutions/doctors/teachers were higher than that in the peasants (both P<0.05); in 2023, the chronic disease prevention and control literacy of the smokers was lower than that in the non-smokers ( P=0.014). Conclusions:The prevalence of chronic diseases among the middle-aged and elderly residents in Wenzhou is relatively low, people with chronic diseases, especially those with multiple chronic diseases, have a low level of chronic disease prevention and control literacy. To prevent and control chronic diseases among them, interventions should be differentiated by the chronic disease status, occupation and household income.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

With the widespread application of ionizing radiation in many industries and the construction of nuclear power plants, the potentials for nuclear accidents is also increasing. In the event of a nuclear accident, rapid classification of a large population is generally involved, so accurate estimation of the radiation dose to the exposed population is the primary task of nuclear emergency response. Based on this need, World Health Organization and International Atomic Energy Agency have each established a worldwide network of biological dosimetry laboratories. In addition, regional networks of biological dosimetry laboratories have been established in the European Union, North America, Latin America and Asia. Based on the long-term organization of national training and assessment of biological dose estimation technology, China will also establish its own network of biological dosimetry laboratories in the future to cope with the emergency disposal needs of potential nuclear accidents. In this paper, the international biodosimetry network and related work will be reviewed, and the idea of establishing biodosimetry laboratory network in China will be elaborated.

OBJECTIVES: To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). METHODS: A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. RESULTS: No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. CONCLUSIONS This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.
Humans ; Mendelian Randomization Analysis ; Autism Spectrum Disorder/genetics* ; Magnesium/blood* ; Zinc/blood* ; Minerals/blood* ; Genome-Wide Association Study ; Selenium/blood*

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.