Neuropsychiatric disorders arise from complex interactions between genetic and environmental factors. DNA methylation, a reversible and environmentally responsive epigenetic regulatory mechanism, serves as a crucial bridge linking environmental exposure, gene expression regulation, and neurobehavioral outcomes. During long-duration deep-space missions, astronauts face multiple stressors-including microgravity, cosmic radiation, circadian rhythm disruption, and social isolation, which can induce alterations in DNA methylation and increase the risk of neuropsychiatric disorders. Genome-wide DNA methylation research can be divided into 3 major methodological stages: Study design, sample preparation and detection, and data analysis, each of which can be applied to astronaut neuropsychiatric health monitoring. Systematic comparison of the Illumina MethylationEPIC array and whole-genome bisulfite sequencing reveals their complementary strengths in terms of genomic coverage, resolution, cost, and application scenarios: the array method is cost-effective and suitable for large-scale population studies and longitudinal monitoring, whereas sequencing provides higher resolution and coverage and is more suitable for constructing detailed methylation maps and characterizing individual variation. Furthermore, emerging technologies such as single-cell methylation sequencing, nanopore long-read sequencing, and machine-learning-based multi-omics integration are expected to greatly enhance the precision and interpretability of epigenetic studies. These methodological advances provide key support for establishing DNA-methylation-based monitoring systems for neuropsychiatric risk in astronauts and lay an epigenetic foundation for safeguarding neuropsychiatric health during future long-term deep-space missions.
DNA Methylation ; Humans ; Space Flight ; Mental Disorders/genetics* ; Epigenesis, Genetic ; Astronauts/psychology* ; Weightlessness/adverse effects* ; Epigenomics

Objective To understand the prevalence of diseases among the elderly in China and the main influencing factors on their ability to live independently in the community, so as to carry out comprehensive assessment and screening of the elderly in the community and achieve healthy aging. Methods The impact of diseases on the health of the elderly in China was quantified through indicators such as disability-adjusted life years, thereby assessing the changing trend of disease burden. Results The disease burden of chronic diseases and injuries is increasing year by year and has become the main disease burden for the elderly. Cardiovascular disease and cancer have the highest proportion of disability-adjusted life years year-round. Disability-adjusted life years for musculoskeletal diseases, traffic injuries, and accidental injuries increased significantly. The incidence of falls and road injuries in the elderly is increasing year by year. The prevalence of oral diseases has always been high and the disability-adjusted life years caused by them have been increasing year by year. At the same time, there are gender differences in prevalence rates and disability-adjusted life years among the elderly. Conclusion Comprehensive assessment of the elderly and timely intervention should be carried out extensively in the community, so as to detect potential problems and functional defects of the elderly early, reduce falls, disability, cognitive impairment, depression and other problems, and at the same time pay attention to the oral health of the elderly and improve their health. People's oral health care knowledge, publicize and popularize correct oral health care habits. Actively promote geriatric medicine education and encourage the whole society to participate in maximizing the maintenance of the functional status and quality of life of the elderly.

Aflatoxin B1(AFB1)is a secondary metabolite produced by Aspergillus aflatoxin and Aspergillus parasiticus.It has strong immunotoxicity and carcinogenicity and seriously harms the health of humans and livestock.Therefore,this study aims to explore the effect of selenomethionine(SeMet)in alleviating AFB1-induced thymic damage.Fifty 35-day-old rabbits were randomly divid-ed into 5 groups,with 10 rabbits in each group.They are the control group,AFB1 group,AFB1+0.2Se group(0.2 mg/kg SeMet),AFB1+0.4Se group(0.4 mg/kg SeMet)and AFB1+0.6Se group(0.6 mg/kg SeMet).The test period was 21 d.On the 17th day,each rabbit in the AFB1 group and each SeMet group was gavaged with AFB1(0.3 mg/kg)every day for 5 consecutive days.Rabbit thymus tissue was taken for HE,TUNEL and PCNA detection.ELISA was used to detect the ex-pression of inflammatory factors in thymus tissue,and GSH-Px,T-AOC and MDA kits were used to detect oxidative stress indicators in thymus tissue.The results showed that AFB1 exposure caused a very significant increase in MDA levels in rabbit thymus tissue by 116.04％,and a signifi-cant decrease in the activities of antioxidant enzymes GSH-Px and T-AOC by 29.20％and 52.17％respectively.In addition,AFB1 induced an inflammatory response in the thymus,promoting TNF-a secretion to increase by 124.71％,IL-6 by 174.72％,and IL-1β by 62.38％compared with the con-trol group.SeMet pretreatment significantly improved the pathological changes of the thymus in rabbits and reduced its oxidative stress and inflammatory response.Therefore,we confirmed that SeMet alleviates AFB1-induced thymic damage and improves the immune performance of rabbits.

Cytokeratin 19(CK19)positivity in tumor cells of hepatocellular carcinoma(HCC)is associated with high aggressiveness and poor prognosis.Noninvasive and accurate imaging prediction of CK19 expression is essential for scheming appropriate treatments and improving prognosis.The progresses in imaging researches of CK19-positive HCC were reviewed in this article.

A patient with advanced lung adenocarcinoma developed symptoms of frequent urination and urgent urination after 14 cycles of Pembrolizumab combined with chemotherapy. After making comprehensive analysis of the results of urine routine test, renal function, cystoscope and computed tomography (CT) examination, immune checkpoint inhibitors related cystoureteritis and acute kidney injury were considered. The patient's symptoms were relieved after discontinuation of Pembrolizumab combined with chemotherapy. However, the symptoms of urinary irritation worsened significantly after rechallenging Pembrolizumab combined with chemotherapy, and the symptoms was relieved after corticosteroids treatment. If patients develop urinary symptoms during immune checkpoint inhibitors treatment, immune checkpoint inhibitors related cystoureteritis should be considered for early differential diagnosis in order to implement appropriate treatment.
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Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/pathology* ; Adenocarcinoma of Lung/drug therapy* ; Tomography, X-Ray Computed

Objective:To investigate the effects of genomic location of a foreign gene in Shanghai-191 strain measles virus (MV) vector on gene expression and virus replication.Methods:The nucleotide sequence encoding S1 protein of SARS-CoV-2 was inserted at different positions in MV antigenome (the upstream of the N gene, between P and M genes, between H and L genes), and co-transfected into 293T cells with helper plasmids coding T7 RNA polymerase and N, P, and L proteins, respectively. The transfected cells were lysed and the supernatants were used to infected Vero cells to harvest recombinant viruses. S1 proteins expressed by the recombinant viruses were identified by RT-PCR, indirect immunofluorescence assay, Western blot and ELISA. Growth kinetics of the recombinant viruses were analyzed.Results:Recombinant viruses were failed to be rescued when the S1 protein-coding sequence was cloned into the upstream of N gene. Two recombinant viruses, MV-M-S1 and MV-L-S1, were successfully rescued when cloning the S1 protein-coding sequence into the intergenic region between P and M genes, or H and L genes, and could express S1 protein. MV-M-S1 expressed more S1 protein than MV-L-S1, but the titer of MV-M-S1 was lower.Conclusions:Inserting a foreign gene at different positions in the MV genome might have different effects on gene expression and virus replication. This study provided reference for the subsequent construction of MV vector.

Objective:To construct a recombinant herpes simplex virus 2 (HSV-2) expressing enhanced green fluorescent protein (EGFP) using clustered, regularly interspaced, short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology.Methods:Four strategies for inserting exogenous EGFP gene into HSV-2 genome using CRISPR/Cas9 technology were designed: (1) conventional homology-directed repair: circular two homology arm donor-mediated gene knock-in; (2) linearized single homology arm donor-mediated gene knock-in; (3) homology-independent targeted integration; (4) conventional homology-directed repair-mediated by cell lines stably expressing Cas9 and sgRNA.Results:The recombinant virus HSV-2-EGFP was successfully constructed based on the second, the third and the fourth strategies. The second strategy was the most efficient, followed by the third and the fourth strategies. The purified recombinant virus could stably express green fluorescent protein in seven passages and shared similar growth characteristics in Vero cells to the parental virus.Conclusions:Linearized single homology arm donor could increase the efficiency of gene knock-in, and cell lines stably expressing Cas9 and sgRNA could increase the efficiency of gene knock-in mediated by homology-directed repair.

Objective:To identify the clinical significance of CDK5 in colon cancer tissues.Methods:Two hundred colon cancer tissues were tested for CDK5 expression by immunohistochemistry on tissue microarrays. The correlation between CDK5 expression and clinicopathological features, prognosis and peripheral inflammation-related cells was analyzed.Results:CDK5 was low expressed in 100 cases (50.0%), and high in another 100 cases (50.0%). Longer time to tumor progression ( P=0.026) and overall survival ( P=0.035) were observed in patients with high CDK5 expression. By multivariate analysis , the expression of CDK5 was an independent risk factor for poor prognosis ( HR=0.45,95% CI: 0.21-0.99, P=0.049). The expression of CDK5 was not related to the counts of white blood cells and neutrophils ( P>0.05). Prognosis of patients with a positive lymph node ratio less than 0.15 was significantly better than that of patients with a higher lymph node ratio ( P<0.001). Conclusions:Patients with low CDK5 expression have poor prognosis, and CDK5 expression is not related to the counts of peripheral white blood cells and neutrophils.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with inherited afibrinogenemia. METHODS: For the proband and his family members, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Fibrin(ogen) degradation products (FDPs), D-dimer (D-D), plasminogen activity (PLG:A) and the TT mixed experiment with protamine sulfate were determined with a STAGO-R automatic coagulation analyzer. The activity and antigen of fibrinogen (Fg) in plasma were measured with the Clauss method and immunonephelometry method, respectively. All exons and flanking regions of the fibrinogen genes (FGA, FGB and FGG) were amplified by PCR and directly sequenced. Human Splicing Finder software was used to predict and score the change of splicing site caused by the mutation. RESULTS: The proband showed normal FDPs and D-D but significantly prolonged TT, PT and APTT. The activity and antigen of fibrinogen in plasma were significantly decreased (<0.1 g/L). His young sister and parents showed slightly prolonged TT (18.20-18.50 s) and decreased fibrinogen activity (1.27-1.54 g/L) and fibrinogen antigenic content (1.34-1.56 g/L). Genetic testing revealed that the proband has carried homozygous IVS7-12A>G (g.4147A>G) mutations of the FGG gene, for which his parents and young sister were heterozygous. As predicted by Human Splicing Finder and Mutation Taster software, the variant may generate a new splicing site which can extend the sequence of exon 7 by 11 bp, with alteration of the coding sequence. PROVEAN suggested the variant to be deleterious. CONCLUSION The afibrinogenemia of the proband may be attributed to the FGG IVS7-12A>G variant, which was unreported previously.
Adult ; Afibrinogenemia/genetics* ; Female ; Fibrinogen/genetics* ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

Objective:To investigate the effect of MCC950 (a NLRP3 inflammasome inhibitor) on cognitive impairment in mice with radiation-induced inflammatory brain injury.Methods:Mice were divided into normal (NS) group, whole body irradiation (IR) group and MCC950 intervention post irradiation (IR+ MCC950) group according to the random number table method, with 15 mice in each group. The mice in IR group and IR+ MCC950 group were irradiated with a single dose of 4.0 Gy. The radiation source was 137Cs and the dose rate was 1.118 Gy/min. The mice in NS group were not irradiated. Mice in IR+ MCC950 group were injected intraperitoneally with MCC950 once a day (10 mg/kg each time) from 3 weeks after irradiation. Behavioral tests such as new and old things recognition experiment and social cognition experiment were used to detect the cognitive function of mice. Immunohistochemistry was used to detect the expression of NeuN protein in CA3 area of mouse hippocampus. PCR and Western blot were used to detect the expression of NLRP3 inflammatory body related protein. Results:Compared with NS group, the short-term and long-term recognition index of new and old things in the IR group decreased significantly ( t=4.321, 5.473, P<0.01), and the social cognitive recognition index of the IR group also decreased significantly ( t=2.097, P<0.05). MCC950 treatment reversed the above changes (short-term and long-term new and old thing recognition test: t=5.860, 4.598, P<0.05; new and old position recognition test: t=3.040, P<0.05; social cognition test: t=4.021, P<0.01). The expression of NLRP3, Caspase-1, IL-1 β and IL-18 in mice hippocampus of the IR group was significantly higher than that of the control group ( t=2.699, 8.515, 3.340, 3.950, P<0.05). Compared with NS mice, radiation significantly increased the expressions of Bax, Caspase-3 and PARP1 in hippocampus ( t=3.887, 2.742, 3.287, P<0.05), while MCC950 significantly decreased the expressions of Bax, Caspase-3 and PARP1( t=2.852, 4.090, 9.614, P<0.05). Conclusions:NLRP3 inflammasome inhibitor MCC950 could alleviate radiation-induced cognitive impairment, which may be due to the inhibition of hippocampal inflammatory and neuronal death.