This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

Objective To explore the correlation of RELL1 expression with clinical pathological features and prognosis of patients with colon cancer.Methods Immunohistochemical experiments of the RELL1 protein were performed on tissue chips from 80 colon cancer tissues and 80 adjacent tissues.The relationship between different expression levels of RELL1 protein and clinical pathological parameters was compared.Univariate and multivariate Cox risk proportional regression analyses were conducted on factors affecting the survival of patients with colon cancer.Kaplan-Meier survival curve analysis was conducted on the survival rates of patients with colon cancer and different levels of RELL1 expression.Log rank test was performed to evaluate differences in survival rates.Results The expression of RELL1 in colon cancer tissues was lower than that in adjacent tissues(P<0.05).The expression of RELL1 in cancer tissues is correlated with TNM stage and N stage(P<0.05).The 3-year overall survival(OS)rate of colon cancer patients with high RELL1 expression was higher than that of patients with low RELL1 expression(P<0.05).Multivariate Cox regression analysis showed that low RELL1 expression,advanced age,and high TNM stage were risk factors for poor prognosis in patients with colon cancer(P<0.05).Conclusion The expression of RELL1 is downregulated in colon cancer tissue,and the low RELL1 expression,advanced age,and high TNM stage can lead to adverse outcomes in patients.

Objective To observe the effects of Huoxue Bushen Anshen Prescription on energy metabolism of H9c2 cardiomyocytes with oxidative stress injury.Methods H9c2 cardiomyocytes oxidative stress model was established with H2O2 to simulate myocardial injury.CCK-8 method was used to select the best conditions for modeling and the appropriate concentration of drugs.Cells were divided into normal group,model group,trimetazidine hydrochloride group and Huoxue Bushen Anshen Prescription group.Na+-K+-ATPase activity,real-time ATP generation rate,mitochondrial pressure,gycolysis rate,and long-chain fatty acid oxidationl pressure on H9c2 cardiomyocytes after treatment were performed,and the changes in energy metabolism of cardiomyocytes were observed.Results Compared with the normal group,the Na+-K+-ATPase activity,glycolytic ATP production rate,mitochondrial ATP production rate,basal oxygen consumption,non mitochondrial oxygen consumption,ATP production capacity,cellular reserve respiratory capacity and maximum respiratory capacity of H9c2 cells in the model group decreased,the glycolytic rate slowed down,long chain fatty acid basal respiration,acute response and maximum respiratory value decreased(P<0.05,P<0.01).Compared with the model group,the H9c2 cells in Huoxue Bushen Anshen Prescription group showed an increase in Na+-K+-ATPase activity,an increase in glycolytic ATP production rate and mitochondrial ATP production rate,an increase in basal oxygen consumption,non mitochondrial oxygen consumption,ATP production capacity,cellular reserve respiratory capacity and maximum respiratory capacity,an increase in basal glycolysis rate,and an increase in long-chain fatty acid basal respiration,acute response and maximum respiratory value(P<0.05,P<0.01).Conclusion Huoxue Bushen Anshen Prescription can significantly improve the activity of Na+-K+-ATPase in cH9c2 ardiomyocytes with oxidative stress injury,increase the rate of ATP production,improve mitochondrial pressure,glycolysis rate and oxidation pressure of long chain fatty acids,and improve the energy metabolism of cardiomyocytes.

Objective To explore the mechanism of Huoxue Bushen Anshen Prescription in improving the oxidative damage of H9c2 cells based on AhR-JDP2-Nrf2 axis.Methods H9c2 cells were divided into normal group,model group,TCM group,trimetazidine group,empty plasmid group,overexpression group,TCM+overexpression group and trimetazidine+overexpression group.The oxidative stress model of H9c2 cells was induced with H2O2 to imitate myocardial injury,and the cells were transfected with JDP2 overexpressed gene,intervened with Huoxue Bushen Anshen Prescription and trimetazidine hydrochloride respectively.Apoptosis was detected by flow cytometry,the contents of MDA,SOD and NADPH in cell supernatant were detected by kits,the protein expression of AhR,JDP2,Nrf2 and HO-1 were detected by Western blot,the mRNA expression of AhR,JDP2,Nrf2 and HO-1 were detected by RT-qPCR.Results Compared with the normal group,the early apoptosis rate,late apoptosis rate and total apoptosis rate of H9c2 cells in the model group increased(P<0.01),the contents of MDA,SOD and NADPH in cell supernatant increased(P<0.05),the expression of AhR,JDP2,Nrf2,HO-1 protein and mRNA increased(P<0.05).Compared with the model group,the early apoptosis rate,late apoptosis rate and total apoptosis rate of H9c2 cells in the TCM group and the trimetazidine group significantly decreased(P<0.01),the contents of MDA,SOD and NADPH decreased(P<0.05),the expression of AhR,JDP2,Nrf2 and HO-1 protein and mRNA decreased in the TCM group(P<0.05).Compared with the empty plasmid group,the overexpression group showed an increase in early apoptosis rate,late apoptosis rate and total apoptosis rate of H9c2 cells(P<0.01),an increase in MDA and NADPH content in cell supernatant(P<0.01),an decrease in SOD content(P<0.01),and an increase in the expressions of AhR,JDP2,Nrf2,HO-1 protein and mRNA in H9c2 cells(P<0.05).Compared with the overexpression group,the early apoptosis rate,late apoptosis rate and total apoptosis rate of H9c2 cells in the TCM+overexpression group and the trimetazidine+overexpression group were significantly decreased(P<0.05,P<0.01),the MDA and NADPH contents in cell supernatant were decreased(P<0.01),the SOD content increased(P<0.01),and the expressions of AhR,JDP2,Nrf2,HO-1 protein and mRNA in H9c2 cells decreased(P<0.05).Conclusion Huoxue Bushen Anshen Prescription can regulate the AhR-JDP2-Nrf2 axis by regulating the expression of JDP2,alleviate the oxidative damage of H9c2 cells,reduce the apoptosis of cardiomyocytes,and protect cardiomyocytes.

Objective To compare the detection rates and antimicrobial resistance rates of Klebsiella pneumoniae(KP)between the intensive care unit of The First People's Hospital of Changzhou(CZFPH-ICU)and the American Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ),as well as the changes in the antimicrobial resistance rate of KP and detection rate of carbapenem-resistant KP(CRKP)in CZFPH-ICU.Methods Differences in speci-men distribution and antimicrobial resistance rate of KP detected from CZFPH-ICU and MIMIC-Ⅳ from 2017 to 2019,as well as the changing trends of specimen distribution,antimicrobial resistance rate,detection rates of KP and CRKP from different specimen sources in CZFPH-ICU from 2017 to 2023 were retrospectively analyzed.Results A total of 2 434 strains of KP were detected in CZFPH-ICU from 2017 to 2019,mainly from sputum specimens.A total of 1 137 strains of KP were detected from MIMIC-Ⅳ database,mainly from urine specimens.Compared with MIMIC-Ⅳ,KP detected from CZFPH-ICU showed higher resistance rate to commonly used antimicrobial agents.A total of 4 874 strains of KP were detected from CZFPH-ICU from 2020 to 2023,mainly from sputum specimens.The detection rates of CRKP from sputum,urine,drainage fluid and bile specimens decreased from 17.77％,20.15％,24.22％and 24.07％in 2017-2019 to 12.99％,13.56％,13.63％and 8.00％in 2020-2023,respectively(all P＜0.05).The changing trend of resistance rate of KP isolated from CZFPH-ICU from 2017 to 2023 to commonly used antimicrobial agents such as piperacillin/tazobactam,imipenem,and meropenem increased in 2017-2019,decreased in 2020-2022,and slightly increased in 2023.In 2013,the resistance rates of KP isolated from CZFPH-ICU to ceftazidime/avibactam,polycolistin B and tigacycline were 21.28％,10.22％and 7.03％,respectively.Conclusion In recent 7 years,resistance rate of KP from CZFPH-ICU showed a slow decline trend,but it was still higher than that in foreign MIMIC-Ⅳ database.Hospitals should strengthen various infection prevention and control measures to ef-fectively control KP resistance and infection.

OBJECTIVE: To explore the genetic basis for a child with mental retardation. METHODS: Whole exome sequencing was carried out for the child. Candidate variant was screened based on his clinical features and verified by Sanger sequencing. RESULTS: The child was found to harbor a c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant in the SYNGAP1 gene. Bioinformatic analysis suggested it to be pathogenic. The same variant was not detected in either parent. CONCLUSION The c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant of the SYNGAP1 gene probably underlay the mental retardation in this child. Above finding has expanded the spectrum of SYNGAP1 gene variants and provided a basis for the diagnosis and treatment for this child.
Child ; Humans ; Intellectual Disability/genetics* ; Frameshift Mutation ; High-Throughput Nucleotide Sequencing ; Computational Biology ; Heterozygote ; Mutation ; ras GTPase-Activating Proteins/genetics*

OBJECTIVE: To investigate the value of pretreatment inflammatory-nutritional biomarkers in predicting the pathological response of locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (nCT). METHODS: This retrospective study included eligible participants who underwent nCT followed by radical surgery. Pretreatment inflammatory nutritional biomarkers were calculated within one week prior to nCT. Correlations between biomarkers and pathological responses were analyzed. The cut-off values of the pretreatment biomarkers for predicting non-response were determined using receiver operating characteristic (ROC) curve analysis. The inflammation-nutrition score was calculated using the lymphocyte level, neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI). RESULTS: A total of 235 patients were retrospectively recruited between January 2017 and September 2022. Lower lymphocyte levels, lymphocyte monocyte ratio (LMR), and PNI, and higher NLR and platelet-to-lymphocyte ratio (PLR) were observed in patients without response. Multivariate logistic regression analysis revealed that NLR could independently predict non-response to nCT in patients with LARC. The sensitivity and specificity of the inflammation-nutrition score for predicting nonresponse were 71.2% and 61.7%, respectively. CONCLUSION The pretreatment inflammation-nutrition score is a practical parameter for predicting non-response to nCT in patients with LARC. Patients with high scores were more likely to respond poorly to nCT.
Humans ; Retrospective Studies ; Neoadjuvant Therapy ; Lymphocytes ; Biomarkers ; Rectal Neoplasms/pathology*

Cordyceps， a unique precious Chinese herbal medicine in China， has the effects of tonifying the kidney and lungs， stopping bleeding， and resolving phlegm. It has definite clinical effects on diabetes， respiratory diseases （such as chronic obstructive pulmonary disease）， chronic kidney diseases， slow arrhythmia， and hyperlipidemia. We searched China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SpringerLink （Biomedical Sciences）， Embase， Proquest （Life Sciences）， PubMed， Cochrane Library， and SinoMed for the research on the arsenic content in Cordyceps. According to statistical analysis， arsenic in Cordyceps mainly exists in the non-toxic or low-toxic form. The arsenic-containing compounds in Cordyceps may be an arsenic-sugar compound with anticancer effect. The inorganic arsenic content in Cordyceps is lower than the arsenic standard stipulated by the State Food and Drug Administration. It remains uncertain whether different measurement methods can affect the results. The total arsenic content varies in Cordyceps from different producing areas， and the general rule of total arsenic content in Cordyceps produced in different provinces， districts， and counties cannot be obtained from the results of the existing studies. The arsenic content in Cordyceps is mainly concentrated in the insect part， which is significantly different from that in stroma， and no arsenic is detected in the mycelia. The soil arsenic content in the growing areas is generally high， which may be a main reason for the high arsenic content in Cordyceps. As a valuable medicinal material for tonifying and nourishing， Cordyceps still plays an irreplaceable role in disease prevention， health care， chronic disease management， and rehabilitation.

This article reviews the concept of telenursing, the application status of telenursing in elderly cancer patients and its influencing factors, and puts forward the suggestions that improve the application ability of intelligent technology in elderly cancer patients, improve the operability of intelligent system, enrich the types and contents of telenursing services, ensure the quality of information, protect privacy security, increase social support and improve social participation so as to provide reference for the application of telenursing in elderly cancer patients.