BACKGROUND: Lung adenocarcinoma (LUAD) is the predominant subtype of non-small cell lung cancer (NSCLC). Damage-specific DNA binding protein 1 (DDB1), as a core protein of the CUL4-DDB1 ubiquitin ligase complex, is involved in the regulation of DNA damage repair, epigenetic modification, and cell cycle checkpoint activation. While the involvement of DDB1 in tumour progression through DNA repair and RNA transcriptional regulation has been reported, its expression and role in LUAD remain to be elucidated. This study aims to investigate the expression and role of DDB1 in LUAD. METHODS: The expression, clinicopathological features and prognosis of DDB1 in LUAD were analysed using databases such as UALCAN, Kaplan-Meier Plotter and GEPIA; The interaction network and enriched functional pathways were constructed by GeneMANIA and Metascape; the correlation between DDB1 and immune cells by combining with TISIDB infiltration was evaluated, and the clustering results of cell subtypes and the expression of DDB1 in different immune cell subpopulations were analysed by single-cell sequencing; finally, tissue microarrays were used to further verify the expression and prognostic value of DDB1 in LUAD. RESULTS: The mRNA and protein expression of DDB1 in LUAD tissues were significantly higher than those in normal tissues (P<0.01), and the high expression correlated with later clinical stage (P<0.001), lymph node metastasis (P<0.001) and poor prognosis (P<0.001). Functional enrichment showed that DDB1 was involved in DNA repair and RNA transcriptional regulation, and TISIDB evaluation revealed that DDB1 was negatively correlated with the expression level of immune cells, suggesting the potential regulation of the immune microenvironment. Single cell analysis showed that DDB1 was mainly expressed in T cells, alveolar macrophages and dendritic cells. Tissue microarrays confirmed that overall survival was shorter in the DDB1 high expression group (P<0.001), and Cox multifactorial analysis showed that DDB1 was an independent predictor of LUAD prognosis. CONCLUSIONS DDB1 is highly expressed in LUAD, which is associated with poor prognosis, and is closely related to tumor immune cell infiltration, and is involved in tumourigenesis and development through DNA repair and RNA transcriptional regulation. DDB1 can be used as a potential prognostic marker and therapeutic target for LUAD.
Humans ; Adenocarcinoma of Lung/immunology* ; DNA-Binding Proteins/metabolism* ; Lung Neoplasms/diagnosis* ; Gene Expression Regulation, Neoplastic ; Prognosis ; Male ; Female ; Middle Aged

Objective To explore the relationship between serum S100 calcium-binding protein(S100)A4,S100A12 and the infection type and prognosis of neonatal infectious pneumonia(NIP).Methods A total of 300 children with NIP admitted to the Neijiang Second People's Hospital from January 2021 to March 2024 were selected and divided into the bacterial infection group(214 cases)and the non-bacterial infection group(86 cases)according to the types of pathogenic bacteria.Another 150 healthy newborns in the same hospital during the same period were selected as the control group.The levels of serum S100A4 and S100A12 were de-tected by enzyme-linked immunosorbent assay.Pearson correlation analysis was conducted to examine the cor-relations between serum S100A4,S100A12 and procalcitonin(PCT),white blood cell count(WBC),albumin(Alb),and platelet count(PLT).The receiver operating characteristic(ROC)curve was used to evaluate the differential value of serum S100A4,S100A12,PCT,WBC,Alb,and PLT alone and in combination for NIP bac-terial infection.According to the prognosis,children with NIP were divided into the poor prognosis group(63 cases)and the good prognosis group(237 cases).Multivariate Logistic regression model was used to analyze the influencing factors of poor prognosis in children with NIP,and ROC curve was used to analyze the value of each factor in predicting poor prognosis in children with NIP.Results The levels of serum S100A4,S100A12,PCT,WBC,and PLT in the bacterial infection group were higher than those in the non-bacterial infection group and the control group,while Alb was lower than that in the non-bacterial infection group and the control group,the differences were statistically significant(P<0.05).Pearson correlation analysis showed that serum S100A4 and S100A12 in children with NIP were positively correlated with PCT,WBC and PLT(P<0.05),and negatively correlated with Alb(P<0.05).The results of ROC curve analysis showed that the area under the curve(AUC)of serum S100A4 and S100A12 in differentiating NIP infection types was slightly lower than that of PCT,WBC,Alb,and PLT in differentiating NIP infection types.The results of multivariate Logistic re-gression analysis showed that elevated S100A4,elevated S100A12,elevated PCT,bacterial infection,and lung consolidation were independent risk factors for poor prognosis in children with NIP(P<0.05).The AUC of bacterial infection,lung consolidation,PCT,S100A4,and S100A12 for predicting the poor prognosis of chil-dren with NIP was 0.903.It was greater than the AUC predicted separately by bacterial infection,lung consol-idation,PCT,S100A4,and S100A12 levels(Z=9.989,9.460,5.514,4.084,4.376,P<0.001).Conclusion The combination of serum S100A4 and S100A12 with traditional markers has certain discrimina-tory value for the infection types of NIP,and the levels of serum S100A4 and S100A12 are related to the prog-nosis of NIP.

Objective To understand the changes in self-rated health among middle-aged and elderly individuals in China and the influencing factors,providing a reference for improving health and promoting healthy aging.Methods Using data from the China Health and Aged Care Tracking Survey(CHARLS)from 2011 to 2020,this study analyzed 3595 middle-aged and elderly individuals(≥45 years old)who participated in all five rounds of the survey from 2011 to 2020.Univariate analysis and multinomial logistic regression were employed to analyze the influencing factors of self-rated health changes.Results Among the 3 595 middle-aged and elderly individuals,26.54％reported an increase in self-rated health,28.40％reported a decrease,and 45.06％reported no change.The multinomial logistic regression results indicated that compared to those with unchanged self-rated health,individuals whose self-rated health declined were more likely to have an increased number of Activities of Daily Living(ADLs),a higher number of chronic diseases,not engaging in at least 10 minutes of light physical activity per week,and a decline in life satisfaction levels.The odds ratios for these factors were 1.415(OR=1.415,95％CI:1.181～1.694),1.479(OR=1.479,95％CI:1.225～1.785),1.454(OR=1.486,95％CI:1.172～1.804),and 1.263(OR=1.237,95％CI:1.043～1.530),respectively.In contrast,individuals whose self-rated health improved,compared to those with unchanged health,were more likely to report an increase in life satisfaction levels,while an increase in ADLs and chronic diseases negatively impacted self-rated health improvement.The odds ratios for these factors were 1.698(OR=1.698,95％CI:1.425～2.023),0.769(OR=0.769,95％CI:0.646～0.915),and 0.689(OR=0.689,95％CI:0.549～0.865),respectively.Conclusion From 2011 to 2020,the self-rated health of middle-aged and elderly individuals in China has slightly declined,with a focus on improving physical health status,increasing physical activity,and addressing mental health as key areas for enhancing self-rated health among the elderly in China.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective To investigate the status of perceived discrimination among HIV-infected people receiving antiviral treatment and analyze its influencing factors,so as to provide reference for reducing discrimination and improving the life quality of HIV-infected people.Methods The multi-stage stratified cluster sampling method was used to select HIV-infected individuals from designated hospitals in three cities and counties in Yunnan Province,as well as from designated township health centers,for face-to-face survey interviews.The questionnaire included socio-demographic characteristics,AIDS infection disease characteristics,Berger AIDS perceived discrimination Scale and Xiao Shui Yuan Social Support Rating Scale.The influencing factors of perceived discrimination were analyzed by multiple linear regression.Results There were 633 valid questionnaires.The perceived discrimination score of HIV-infected people was(111.11±19.43),which was at a medium high level,and the dimension with the highest average score was fear of publicity.Multiple regression showed that middle-aged people,those who do not participate in group activities and those who have less social support had higher perceived discrimination(P＜0.05).Conclusion The perception discrimination of AIDS patients in Yunnan Province is high.In the prevention and control of AIDS,it is necessary to actively organize and participate in group activities,improve social support and pay attention to middle-aged AIDS patients.

OBJECTIVE:To elucidate the efficacy and mechanism of Hugan tablets in hepatoprotective effects from perspective of metabolic pathways. METHODS:36 male rats were randomly divided into normal group (0.5%sodium carboxymethyl cellu-lose),model group(0.5%sodium carboxymethyl cellulose)and Hugan tablets group(1.7 g/kg),12 in each group,intragastrically administrated once a day,for 9 d. After 1 h of last administration,rats in model group and Hugan tablets group were intraperitone-ally injected 50%CCl4 peanut oil solution 1 mL/kg to induce liver injury. After 24 h of modeling,malondialdehyde(MDA),super-oxide dismutase(SOD),glutathione peroxidase(GSH-Px)levels in liver tissue of rats were detected. Nuclear magnetic resonance spectroscopy(1H-NMR)metabolomics technique was adopted to establish the serum and liver metabolite profiles of rats,and the ef-fects of Hugan tablets on changes of metabolic profile and potential biomarkers in serum and liver of rats with CCl4-induced acute liver injury were analyzed. RESULTS:Compared with normal group,MDA level in liver tissue of rats in model group was signifi-cantly increased(P<0.05),SOD and GSH-Px levels were significantly reduced(P<0.05). Both body physiology and material me-tabolism of rats were obviously changed,and levels of 11 metabolic potential biomarkers in serum and 14 metabolic potential bio-markers in liver were significantly increased/decreased (P<0.05). Compared with model group,MDA level in liver tissue in Hugan tablets group was significantly reduced(P<0.05),SOD and GSH-Px levels were significantly increased(P<0.05). Serum and liver metabolism tended to be normal,6 metabolic potential biomarkers(isoleucine,leucine,3-hydroxybutyrate,acetone,ace-toacetate,choline) in serum and 8 metabolic potential biomarkers (3-hydroxybutyrate,alanine,glutamate,pyruvate,succinate, choline,lactate,glucose)in liver got significant callback(P<0.05). CONCLUSIONS:The hepatoprotective mechanism of Hugan tablets may be associated with antioxidative stress and regula-tion of lipid metabolism,glucose metabolism and amino acid metabolism.

An important index determination for clinical diagnosis of renal function is to assay the creatinine concentration in serum. In the analytical process applied with coupled-enzyme, the quality control of sarcosine oxidase (SOX) as a key enzyme is the first problem to be solved. In order to establish an efficient and laboratory-scale production of SOX, the recombinant sarcosine oxidase (r-SOX) gene was a high-level expression in E. coli induced with lactose on a large-scale fermentation in 300 L fermenter. The results suggested that the biomass concentration reached OD600 of 22 and the expression of recombinant sarcosine oxidase in E. coli accounted for about 25% of total soluble protein in culture after fermentation. The cell-free extract obtained from high pressure homogenizer was processed by selective thermal denaturation and then purified with Ni-Sepharose FF chromatography. The sarcosine oxidase with 97% purity, 25 U/mg specific activity and 92.4% activity recovery was obtained. The molecular weight with single peptide chain of 53 kD and 55 kD of recombinant sarcosine oxidase was assessed by SDS-PAGE in presence or absence of 2-mercaptoehanol and Sephacryl S-200 chromatography. This sarcosine oxidase was found to be a conjugated protein, yellow enzyme, which combined with FAD as prosthetic group by covalent linkage. The contaminant of catalase was not detected in the sample pool of this enzyme. In addition, a further test to the thermal stability of sarcosine oxidase was done. According to the above results, the development and utilization of this enzyme has been set up on a reliable foundation.
Escherichia coli ; Fermentation ; Recombinant Proteins ; biosynthesis ; Sarcosine Oxidase ; biosynthesis

OBJECTIVETo evaluate the therapeutic effect of ulinastatin combined with thymosin α1 in the treatment of severe sepsis in rats.

METHODSNormal Wistar rats were subject to cecal ligation and puncture (CLP) to establish models of severe sepsis. The rats were then randomized into 4 groups for treatment with saline (control), ulinastatin, thymosin α1, or the combination of the latter two injected through the caudal vein or subcutaneously at 6, 24, 48 and 72 h after modeling. The mortality rate was recorded daily and the rats were executed at 24, 48, 72 and 96 h after CLP to harvest the heart, liver, spleen, lung, kidney and small intestines for pathological examination. The spleen of the rats were taken for detection of apoptosis of the spleen cells.

RESULTSThe mortality rate of the septic rats in the combined treatment group was decreased significantly (P=0.0325). The control group showed the most severe organ damage, which was moderate in single drug treatment group and the mildest in combined treatment group. Obvious spleen cell apoptosis was found in the control group, and was significantly ameliorated in the combined treatment group[(47.4∓10.9)% vs (39.3∓11.4)%, P=0.0000].

CONCLUSIONCombined treatment with ulinastatin and thymosin α1 can significantly improve the prognosis and ameliorate organ damage and spleen cell apoptosis in rats with sever sepsis.

Animals ; Apoptosis ; Drug Therapy, Combination ; Glycoproteins ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Sepsis ; drug therapy ; pathology ; Spleen ; cytology ; pathology ; Thymosin ; analogs & derivatives ; therapeutic use

Objective To detect the changes of interleukin-18 (IL-18) in plasma of trauma patients and evaluate their value in early warning of organ dysfunction. Methods A prospective study was carried out in 54 trauma patients admitted in from March 2001 to September 2002, which were divided into low injury severity score(ISS) group (Group L-ISS) and high ISS group (Group H-ISS). ELISA was applied to measure the level of IL-18 of blood samples that were collected on arrival, at days 4, 7 and 14 following admission. In the meantime, IL-18 level of plasma samples from patients with systemic inflammatory response syndrome (SIRS), sepsis and multiorgan dysfunction syndrome (MODS) was retrospectively analyzed so as to calculate the critical value of IL-18 in predicting organ dysfunction. Results After trauma, IL-18 concentration of plasma reached peak at days 4 and 7, and decreased gradually at day 14, which was significantly related to SIRS, sepsis and MODS, respectively. The IL-18 level was high relatively in plasma from patients with organ dysfunction. The higher IL-18 level in plasma within seven days after trauma indicated the severer organ dysfunction. Conclusion IL-18 is sensitive in early warning of organ dysfunction after trauma.

OBJECTIVEVerotoxin-producing Escherichia coli (VTEC) strains of serotype O157 : H7 have been implicated in a wide spectrum of diseases, including blood diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS). To further explore the pathological role of verotoxin (VT) in HUS and other VTEC associated diseases, we investigated the effects of recombinant verotoxin 2 (rVT2) on the biological activity of neutrophils.

METHODSThe technique of flow cytometry, a fluorescent probe 2,7-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF/AM), and the assay of reduced cytochrome c to detect superoxide production were used in this study.

RESULTSgammaVT2 significantly inhibited spontaneous apoptosis in neutrophils. Neutrophils with prolonged survival due to gammaVT2 maintained various biological functions, such as the expression of adhesion molecules (shading CD62L and raising CD11b/CD18), adherence to human umbilical vein endothelial cells (HUVECs), and generation of superoxide (O(2)(-)).

CONCLUSIONProlongation of the functional life-span of neutrophils by gammaVT2 may accelerate inflammatory responses at sites of inflammation. This may play a crucial role in neutrophil-mediated tissue injury in HUS and other VTEC-associated diseases.

Apoptosis ; drug effects ; Cell Adhesion ; Endothelium, Vascular ; cytology ; Humans ; Neutrophils ; drug effects ; physiology ; Recombinant Proteins ; toxicity ; Shiga Toxin 2 ; toxicity ; Superoxides ; metabolism