The distributioa of Se in Hb and the effects of Se intake and its chemical forms oil the distribution were studied. The results showed that Se in human Hb was all located in globin and divided equally in a and ? chains. However, a part of Se could fall from Hb during the process of isolation when more Se as SeMet was taken and "excess" Se appeared in Hb. It was implicated that there were at least two kinds of linkage between Se and Hb --tight and loose.Regarding the components of amino acid in ? and ? chains, we assumed that a tight linkage between Se and Hb was in the form of SeMet, which was incorporated into Hb by dietary Se during the synthesis of Hb; the loose linkage was formed by a part of "excess" Se and CyS, especially No.93 CyS in ? chain, being unstable sclcnotrisulf ide or selenopersulfide, which broke easily by reduction during isolation. They might be utilized first by human body when Se was required.

Objective To investigate and analyze the expression of α-SMA and PCNA in abdominal aorta and renal artery in obstructive sleep apnea syndrome(OSAS)combined with hypertension rats. Methods 36 SD rats were randomly divided into normal control group and model group. The model group was subjected to intermittent hypoxia condition for 8h everyday. Rat tail artery pressure was monitored every week and all subjects were sacrificed at 12th week. The level of TNF-α, IL-6, IL-10 and hs-CRP expression in serum were measured by ELISA method. Immunohistochemical analysis was performed on α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA). Results Compared with control group,model rats blood pressure increased significantly (P < 0.01) when exposed for 4 weeks under intermittent hypoxia condition,and reached the peak value of 186mmHg at 12 weeks. The level of TNF-α, IL-6 , IL-10 and hs-CRP in serum were higher than in control group (P < 0.01). Immunohistochemical staining showed that the expression of α-SMA in abdominal aorta decreased more significantly than control group (P < 0.05),while there was a stronger positive expression of PCNA in model group than those in control (P < 0.05). In addition,compared with control rats, model rats showed a higher expression of α-SMA and PCNA significantly in renal artery(P < 0.05). Conclusion The intermittent hypoxia condition could result in higher blood pressure,while the different expression of α-SMA and PCNA illustrate that high pressure show different reconstruction performance in different vascular,underlying different molecular mechanism.

This study was aimed to compare the pharmacokinetics (PK) of Shengmai injection and Shenmai injection with a single injection administration using a constant speed in subjects with stable angina pectoris.A total of 20 subjects with stable angina pectoris were divided into two groups.Each group was administered with Shengmai and Shenmai injection.The liquid chromatography-mass spectrometry (LC/MS) was adopted to determine concentrations of ginsenosides in plasma at different time points.PK parameters were calculated for comparison.The results showed that after a single intravenous infusion of Shengmai and Shenmai injection,the Cm.of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in Shenmai group were higher than those of the Shengmai group with statistical significance (P ≤0.05).There were differences on the T1/2 of ginsenoside Rg1,AUC0-144h and CL of ginsenoside Rc,as well as Tmax of ginsenoside Rd (P ≤ 0.05).However,there was no significant difference shown on other PK parameters.It was concluded that after a single Shengmai or Shenmai injection,there were PK differences of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in the human body.The clinical medication selection should be based on syndrome differentiation and treatment of patients.

Objective: To understand the changes of smoking behavior among primary and middle school students in Beijing during 2005-2015. Methods: The primary and middle schools in Beijing were classified and then taken as a sampling frame. Twophase stratified random cluster sampling was conducted with school as primary sampling unit (PSU) and class as the minimum sampling unit, respectively. Beijing Schoolbased Smoking Monitoring Questionnaire was surveyed in 2005 and 2005, 2010, 2011, 2013 and 2015 anonymously. Results: In 2015, the smoking rate among primary and middle school students in Beijing was 9.41%. Among them, for primary, junior, high school and vocational high school students, the rates were 7.05%, 7.06%, 12.41% and 34.11%, respectively. The smoking rates were now 3.26%, with 1.99%, 1.80%, 3.48% and 20.22%, respectively, among primary, middle and high school and vocational high school students. male, vocational school students were more likely to report smoking across six waves of surveillance. Results from the surveillance in 2015 showed a decreasing trend in ever smoking rate and current smoking rate compared with previous survey. About half of the current student smokers were reported to take 1 cigarette/day, and about 10% smokers were reported to take 10 cigarettes/day. Students were most likely to smoke at home(24.02%), followed by smoking at schools(12.74%). The percentage of buying cigarettes by themselves was increased from 17.10% in 2008 to 66.09% in 2015. Conclusion From 2005 to 2015, both ever smoking and current smoking rate among middle school students in Beijing decreased in general, however smoking among vocational high school students warrants further attention.

Agrobacterium tumefaciens-mediated transformation system has been widely applied. However, the function of target gene is affected by multiple factors. With this system, we obtained a transgenic rice line CX8621 carrying the bacterial blight resistance gene Xa21. In previous work, we have confirmed that it was selectable maker-free and vector backbone-free. And after 16 generations of breeding, it still maintained perfect resistance to bacterial blight disease. On this basis, we analyzed the integration and expression of Xa21 in CX8621 at the present study. First, based on the border sequences of plasmid pBXa21 and Xa21, we designed nested primers and assured the integrity of Xa21 in CX8621. Second, we cloned the flanking sequences and located Xa21 on chromosome 2 using improved Tail-PCR. Then we analyzed the expression pattern of Xa21 in several tissues and at different developmental stages by RT-PCR. The results show that Xa21 can be stably expressed in CX8621, agreeing well with the disease resistance response as reported previously. In addition, we detected the protein levels of XA21 in CX8621 with antibody of natural XA21 protein. Surprisingly, no XA21 protein was detected in the seeds of CX8621. Thus, the integration and expression analysis of Xa21 in CX8621 provided a part of scientific evidences for the safety assessment of genetically modified rice.
Animals ; DNA Primers ; Disease Resistance ; genetics ; Oryza ; genetics ; Plant Proteins ; genetics ; Plants, Genetically Modified ; genetics ; Polymerase Chain Reaction ; Protein-Serine-Threonine Kinases ; genetics ; Seeds

ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors