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*

Objectives:To investigate the effect of interferon-γ(IFN-γ)on the repair of dental pulp injury.Methods:hDPSCs were isolated and cultured,and the hDPSCs were divided into control group,0.05 ng/mL IFN-γ group,0.5 ng/mL IFN-γ group,5 ng/mL IFN-γ group and 0.5 ng/mL IFN-γ+PDTC group.Transwell was used to detect the effect of IFN-γ on the migration abil-ity of human dental pulp stem cells,alizarin red staining was used to evaluated the influence of IFN-γ on the osteogenic differentia-tion of hDPSCs,and the expression of protein related to Wnt/β-catenin signaling pathway in cells was detected by Western blot.The rat dental pulp mechanical injury model was established,and the 3D cultured hDPSCs cell mass and hDPSCs cell mass with 0.5 ng/mL IFN-γ were placed in the cavity of the established rat dental pulp injury model.The cavity was filled with glass ionomer,and HE staining was used to compare the repair of dental pulp tissue in each group of rats.Results:The number of migrating cells in dif-ferent concentrations of IFN-γ groups was significantly higher than that in the control group,and the difference was statistically signif-icant(P＜0.05),and the number of migrated cells in the 0.5 ng/mL IFN-γ group was more than that in the 0.05 ng/mL IFN-γgroup and the 5 ng/mL IFN-γ group(P＜0.05).Compared with the control group,the mineralized nodules and osteoblastic differ entiation of hDPSCs in different concentrations IFN-γgroups were significantly inhibited(P＜0.05).Compared with the 0.5 ng/mL IFN-γ group,the mineralized nodule formation and osteogenic differentiation of hDPSCs in the 0.5 ng/mL IFN-γ+PDTC group were enhanced(P＜0.05).Compared with the control group,the ALP activity of IFN-γ group and IFN-γ+PDTC group was significantly lower(P＜0.05),and the ALP activity of IFN-γ+PDTC group was higher than that of IFN-γgroup,and the difference between groups was statistically significant(P＜0.05).Compared with the control group,the protein ex-pression levels of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ group and IFN-γ+PDTC group were significantly decreased,while the GSK-3β and p-GSK-3β had increased,and the difference between the groups was statistically significant(P＜0.05),the protein expressions of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ+PDTC group were significantly higher than those in the IFN-γ group,while the protein expression levels of p-GSK-3β and GSK-3β were lower than those in the IFN-γ group,and the differences between the groups were statistically significant(P＜0.05).Compared with the control group,the inflammatory response in the dental pulp mechanical injury model of the IFN-γ group was aggravated,and the dentin formation was significantly inhibited.Conclusion:IFN-γ can promote the migration of hDPSCs and inhibit the osteogenic differentiation of hDP-SCs,and IFN-γ has an inhibitory effect on the formation of restorative dentin after pulp injury,which may be related to the expres-sion regulation of Wnt signaling pathway.

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 understand the distribution characteristics of fungi on object surface in hospital environ-ment,and provide reference for the scientific and precise formulation of environment control strategies based on fun-gal in clinic.Methods From December 7 to 23,2023,a total of 60 environmental specimens of 19 categories in 6 departments of a large tertiary first-class hospital were collected and divided into water-related environmental speci-men group,complete facade environmental specimen group,and sanitary ware environmental specimen group.18S rRNA sequencing was performed on specimens with fungi detected.Results Fungal detection rate of environmental specimens was 20.00％(12/60).Sink in the department of endocrinology had the highest fungal colony count(15 CFU/cm2),followed by the air outlet of air disinfection device in the department of thoracic surgery and the in-ternal part of a faucet in the department of endocrinology(both 10 CFU/cm2).The water-related environmental specimen group detected most diverse fungal genera(14 species),with high relative abundances of Aspergillus(100％),Meyerozyma(99.06％),Ophiocordyceps genus(95.63％),and Kodamaea(87.86％).The air outlet of air disinfection device was detected with a high abundance of Chaetomium(44.08％)and Corollospora(39.71％).There was no statistically significant difference in the α-diversity(Shannon and Simpson indices,P values of 0.661 and 0.568,respectively)and β-diversity(P=0.712)among the three environmental specimens.Conclusion Under the routine implementation of basic environmental cleaning and disinfection in medical institutions,fungi are in a low prevalence in the environment.However,moist surfaces and air disinfection device are prone to fungal colonization,and it is necessary to strengthen daily monitoring and take corresponding intervention measures to reduce the risk of infection.

Objective To understand the distribution characteristics of fungi on object surface in hospital environ-ment,and provide reference for the scientific and precise formulation of environment control strategies based on fun-gal in clinic.Methods From December 7 to 23,2023,a total of 60 environmental specimens of 19 categories in 6 departments of a large tertiary first-class hospital were collected and divided into water-related environmental speci-men group,complete facade environmental specimen group,and sanitary ware environmental specimen group.18S rRNA sequencing was performed on specimens with fungi detected.Results Fungal detection rate of environmental specimens was 20.00％(12/60).Sink in the department of endocrinology had the highest fungal colony count(15 CFU/cm2),followed by the air outlet of air disinfection device in the department of thoracic surgery and the in-ternal part of a faucet in the department of endocrinology(both 10 CFU/cm2).The water-related environmental specimen group detected most diverse fungal genera(14 species),with high relative abundances of Aspergillus(100％),Meyerozyma(99.06％),Ophiocordyceps genus(95.63％),and Kodamaea(87.86％).The air outlet of air disinfection device was detected with a high abundance of Chaetomium(44.08％)and Corollospora(39.71％).There was no statistically significant difference in the α-diversity(Shannon and Simpson indices,P values of 0.661 and 0.568,respectively)and β-diversity(P=0.712)among the three environmental specimens.Conclusion Under the routine implementation of basic environmental cleaning and disinfection in medical institutions,fungi are in a low prevalence in the environment.However,moist surfaces and air disinfection device are prone to fungal colonization,and it is necessary to strengthen daily monitoring and take corresponding intervention measures to reduce the risk of infection.

Objectives:To investigate the effect of interferon-γ(IFN-γ)on the repair of dental pulp injury.Methods:hDPSCs were isolated and cultured,and the hDPSCs were divided into control group,0.05 ng/mL IFN-γ group,0.5 ng/mL IFN-γ group,5 ng/mL IFN-γ group and 0.5 ng/mL IFN-γ+PDTC group.Transwell was used to detect the effect of IFN-γ on the migration abil-ity of human dental pulp stem cells,alizarin red staining was used to evaluated the influence of IFN-γ on the osteogenic differentia-tion of hDPSCs,and the expression of protein related to Wnt/β-catenin signaling pathway in cells was detected by Western blot.The rat dental pulp mechanical injury model was established,and the 3D cultured hDPSCs cell mass and hDPSCs cell mass with 0.5 ng/mL IFN-γ were placed in the cavity of the established rat dental pulp injury model.The cavity was filled with glass ionomer,and HE staining was used to compare the repair of dental pulp tissue in each group of rats.Results:The number of migrating cells in dif-ferent concentrations of IFN-γ groups was significantly higher than that in the control group,and the difference was statistically signif-icant(P＜0.05),and the number of migrated cells in the 0.5 ng/mL IFN-γ group was more than that in the 0.05 ng/mL IFN-γgroup and the 5 ng/mL IFN-γ group(P＜0.05).Compared with the control group,the mineralized nodules and osteoblastic differ entiation of hDPSCs in different concentrations IFN-γgroups were significantly inhibited(P＜0.05).Compared with the 0.5 ng/mL IFN-γ group,the mineralized nodule formation and osteogenic differentiation of hDPSCs in the 0.5 ng/mL IFN-γ+PDTC group were enhanced(P＜0.05).Compared with the control group,the ALP activity of IFN-γ group and IFN-γ+PDTC group was significantly lower(P＜0.05),and the ALP activity of IFN-γ+PDTC group was higher than that of IFN-γgroup,and the difference between groups was statistically significant(P＜0.05).Compared with the control group,the protein ex-pression levels of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ group and IFN-γ+PDTC group were significantly decreased,while the GSK-3β and p-GSK-3β had increased,and the difference between the groups was statistically significant(P＜0.05),the protein expressions of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ+PDTC group were significantly higher than those in the IFN-γ group,while the protein expression levels of p-GSK-3β and GSK-3β were lower than those in the IFN-γ group,and the differences between the groups were statistically significant(P＜0.05).Compared with the control group,the inflammatory response in the dental pulp mechanical injury model of the IFN-γ group was aggravated,and the dentin formation was significantly inhibited.Conclusion:IFN-γ can promote the migration of hDPSCs and inhibit the osteogenic differentiation of hDP-SCs,and IFN-γ has an inhibitory effect on the formation of restorative dentin after pulp injury,which may be related to the expres-sion regulation of Wnt signaling pathway.

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 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 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.