ObjectiveTo explore the protective effect of glucocorticoid-induced transcription factor 1 （GLCCI1） on cognitive dysfunction in diabetic mice and its mechanism. MethodsTwenty-four C57BL/6J mice were randomly divided into 4 groups， namely Control， DM， DM+AAV-Glcci1， and DM+AAV-NC. The Control group was intraperitoneally injected with saline， while the other groups were all injected with streptozotocin （STZ）. Two weeks after successful modeling， the DM+AAV-Glcci1 group was brain stereotactic injected with Glcci1 overexpressing adeno-associated virus， and the DM+AAV-NC group was stereoscopically injected with the control virus. After 12 weeks， the Morris water maze test was used to evaluate the learning and memory abilities of mice in each group. Subsequently， the localized expression of GLCCI1 in the hippocampus were determined by immunofluorescence and immunohistochemistry experiments. The myelin morphology in the hippocampus was observed by LFB staining， the neuronal morphology was observed by Nissl staining， and the myelin-related proteins MBP and CNPase were stained by immunohistochemistry. Molecular docking was used to predict the interaction between GLCCI1 and HSPA5. The expression of endoplasmic reticulum stress-related proteins was detected by Western blot. ResultsThe results of the behavioral experiment showed that compared with the mice in the Control group， DM mice exhibited obvious cognitive dysfunction behaviors （P＜0.000 1）， and the learning and memory abilities of mice improved after overexpression of Glcci1 （P=0.000 7）. The results of immunofluorescence and immunohistochemistry showed that GLCCI1 was expressed in hippocampal neuron cells. Compared with Control mice， the expression level of GLCCI1 in DM mice was significantly downregulated （P＜0.000 1）. The molecular docking results revealed that GLCCI1 interacts with HSPA5. The Western blot results indicated that， compared with the Control group， the expression levels of endoplasmic reticulum stress-related proteins HSPA5 （P＜0.000 1）， ATF4 （P＜0.000 1）， ATF6 （P=0.001 1）， and p-ELF2α/elF2α （P=0.000 1） in the DM group were significantly increased； Compared with the DM group， the expression of the corresponding protein HSPA5 （P＜0.000 1）， ATF4 （P＜0.000 1）， ATF6 （P=0.000 2）， and p-ELF2α/elF2α （P=0.000 1） was significantly down-regulated after overexpression of Glcci1. LFB staining showed that compared with the Control group， the myelin integrity of DM mice decreased significantly （P=0.010 3）， the expressions of myelin-related proteins MBP and CNPase decreased significantly （P=0.000 4， P=0.000 2）， and Nissl staining observed disordered neuronal arrangement. Compared with the mice in the DM group， the myelin integrity in the hippocampal region significantly increased after overexpression of Glcci1 （P=0.000 3）， the expressions of myelin-related proteins MBP and CNPase significantly increased （P=0.001 4， P=0.000 1）， and the ordered arrangement of neurons was observed by Nissl staining. ConclusionThe down-regulation of GLCCI1 expression in hippocampal neurons promotes demyelination of hippocampal neurons and thereby induces diabetic cognitive dysfunction. The specific mechanism may be related to endoplasmic reticulum stress.

Objective: To explore the association between serum nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), NIMA-related kinase 7 (NEK7) and pulmonary fibrosis among patients with coal workers' pneumoconiosis, so as to provide a basis for the assessment of the degree of pulmonary fibrosis. Methods: Coal workers with pneumoconiosis hospitalized in the Second Affiliated Hospital of Xuzhou Medical University from July 2022 to July 2023 were selected by simple random sampling. Data such as age, stage of pneumoconiosis, and dust-exposure duration were collected through the hospital's electronic medical record management system. Venous blood was collected to detect the levels of serum NLRP3 and NEK7. High-resolution computed tomography (HRCT) image data of the chest were obtained through the hospital's imaging reporting system. The left and right lungs were divided into 6 pulmonary regions according to the upper, middle, and lower parts. The pulmonary fibrosis score was quantified according to the proportion of the pulmonary area occupied by HRCT manifestations of pulmonary fibrosis, including reticular shadows, pleural and interlobular septal thickening, traction bronchiectasis, and honeycombing. The association between the levels of serum NLRP3, NEK7, and pulmonary fibrosis was analyzed using a multiple linear regression model. Results: A total of 81 patients with coal workers' pneumoconiosis were included, all of whom were male, with a mean age of (71.46±11.69) years. There were 48, 28, and 5 cases in stage Ⅰ, stage Ⅱ, and stage Ⅲ of pneumoconiosis pathological staging, accounting for 59.26%, 34.57%, and 6.17%, respectively. There were 45 cases of tunneling and coal mining, accounting for 55.56%. There were 41 cases with dust exposure years of ≥30 years, accounting for 50.62%. The median serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis were 2.01 (interquartile range, 2.33) ng/mL and 0.98 (interquartile range, 0.83) ng/mL. The median score of pulmonary fibrosis was 5.00 (interquartile range, 5.50) points. After adjusting for age, stage of pneumoconiosis, type of work and dust-exposure duration, multiple linear regression analysis showed that serum NLRP3 (β'=0.649) and NEK7 (β'=0.346) were positively correlated with the pulmonary fibrosis score. Conclusion The increase in the levels of serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis is related to the increase in the degree of pulmonary fibrosis.

Objective To explore the prognostic value of hemoglobin-albumin-lymphocyte-platelet(HALP)score and geriatric nutritional risk index(GNRI)in elderly patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods A retrospective analysis was conducted on the clinical and follow-up data of 228 elderly AECOPD patients who were admitted to the De-partment of Respiratory and Critical Care Medicine,the Second Affiliated Hospital of Zhengzhou University from September 2018 to March 2022.After discharge,the patients received 1-year follow-up,and were divided into two groups based on their prognosis:good progno-sis group(n=130)and poor prognosis group(n=98),and the data were compared between the two groups.The predictive effect of HALP score and GNRI on poor prognosis in elderly AECOPD patients was analyzed by receiver operating characteristic(ROC)curve.The correlation analysis was used to investigate the relationship between HALP score and GNRI and C-reactive protein(CRP),interleukin-6(IL-6),procalcitonin(PCT),NRS2002,length of hospital stay and prognostic outcomes.Results The levels of body mass index,lymphocyte count,hemoglobin,albumin,GNRI,and HALP score in the good prognosis group were higher than those in the poor prognosis group,and the age,length of hospitalization,NRS2002,neutrophil count,CRP,IL-6,PCT,sputum culture,chest CT combined with inflammation were lower than those in the poor prognosis group,and the differences were statistically significant(P＜0.05).The results of ROC curves indicate that the area under the curve(AUC)of HALP score and GNRI were 0.868 and 0.682 respectively.The results of correlation analysis showed that in elderly patients with AECOPD,both HALP score and GNRI were negatively correlated with CRP,PCT,NRS2002,length of hospitalization,prognostic outcomes,sputum culture,and chest CT with inflammation(P＜0.05),and GNRI was also negatively correlated with IL-6(P＜0.05).Conclusion HALP score and GNRI can predict the prognostic outcome of elderly pa-tients with AECOPD.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Objective The aim of this study was to investigate the effects of LncRNA OTUD6B-AS1 on the proliferation,mi-gration and invasion of lung adenocarcinoma A549 cells.Methods Lung adenocarcinoma A549 cell line was cultured in vitro,and transient transfection of OTUD6B-AS1 and empty plasmid group were used as the control group.Overexpression and control cell mod-els were constructed,and divided into OTUD6B-AS1 overexpression group and empty plasmid group(NC group).The cell model was divided into the empty plasmid group(NC group)and OTUD6B-AS1 overexpression group.The transfection efficiency of OTUD6B-AS1 mRNA was verified through qRT-PCR.The CCK-8 experiment was used to detect the effect of OTUD6B-AS1 on the prolifera-tion activity of lung adenocarcinoma cells,and the Transwell assay was used to detect the effect of OTUD6B-AS1 on the migration and invasion ability of lung adenocarcinoma cells.Results Compared to the NC group,the overexpression OTUD6B-AS1 group had a sig-nificant increase in the expression of OTUD6B-AS1(P<0.05).The CCK-8 assay results showed that the proliferation activity of A549 cells in the OTUD6B-AS1 overexpression group was significantly reduced compared to the NC group(P<0.05).The results of the Transwell assay showed that the OTUD6B-AS1 overexpression group had significantly lower cell migration and invasion abilities than the NC group(P<0.05).Conclusion Overexpression lncRNA OTUD6B-AS1 in lung adenocarcinoma A549 cells can signifi-cantly inhibit the proliferation,migration,and invasion ability of A549 cells.

Non-alcoholic fatty liver disease(NAFLD)has become the most important cause of chronic liver disease,and its pathogenic mechanism is very complex.microRNA(miRNA)are widely distributed non-cod-ing RNA.miRNA play an important regulatory role in the pathogenesis and progression of various chronic liv-er diseases,including NAFLD,and may even be used as diagnostic indicators or even therapeutic targets for liver diseases.As a non-invasive biological indicator,a large number of research data show that miRNA has important clinical value in the diagnosis and prognosis of NAFLD.This article provides a review of the re-search progress related to the pathogenic mechanism and clinical diagnostic value of miRNA in NAFLD.

Amantadine(AMD)residue can accumulate in organisms through the food chain and cause serious harm to human body.AMD can specifically bind to AMD specific aptamer and cause its conformation to change from a random single strand to a stem-loop structure.To avoid the influence of excess nucleotides on binding of aptamer to AMD,the truncation of the AMD original aptamer J was optimized by retaining an appropriate stem-loop structure,and a new type of truncation aptamers was developed in this work.By comparing the truncated aptamer with the original aptamer,it was found that the truncated aptamer J-7 had better affinity and specificity with AMD.The detection limit of AMD was 0.11 ng/mL by using J-7 as specific recognition element and molybdenum disulfide nanosheet(MoS2Ns)as signal amplification element.The developed method base on truncated aptamer J-7 was used for detection of AMD in milk,yogurt and SD rat serum samples for the first time with recoveries of 86.6%-108.2%.This study provided a reference for truncating other long sequence aptamers and provided a more sensitive detection method for monitoring AMD residues in food.

Objective:To evaluate the effects of pulmonary embolism response team (PERT) on the quality of care and clinical outcomes in patients with acute pulmonary embolism.Methods:This was a single-center retrospective cohort study. Patients with acute pulmonary embolism treated in Beijing Anzhen Hospital Affiliated to Capital Medical University from July 5, 2016 to July 4, 2018 were enrolled. Patients with acute pulmonary embolism who had traditional care from July 5, 2016 to July 4, 2017 (before the implementation of PERT) were classified as PERT pre-intervention group. Patients with acute pulmonary embolism who started PERT care from July 5, 2017 to July 4, 2018 were divided into the PERT intervention group. The diagnosis and treatment information of patients was collected through the electronic medical record system, and the quality of care (time from visit to hospitalization, time from hospitalization to anticoagulation initiation, time from visit to definitive diagnosis, total hospital stay, time in intensive care unit (ICU), hospitalization cost) and clinical outcomes (in-hospital mortality and incidence of bleeding) were compared between the two groups.Results:A total of 210 patients with acute pulmonary embolism, aged (63.3±13.7) years old, with 102 (48.6%) female patients were included. There were 108 cases in PERT pre-intervention group and 102 cases in PERT intervention group. (1) Quality of diagnosis and treatment: there was a statistical significance between the two groups in the distribution of time from diagnosis to definitive diagnosis ( P=0.002). Among them, the rate of completion of diagnosis within 24 hours after PERT intervention was higher than that before PERT intervention (80.4% (45/56) vs. 50.0% (34/68), P<0.001). The time from treatment to hospitalization was shorter than that before PERT intervention (180.0 (60.0, 645.0) min vs. 900.0 (298.0, 1 806.5) min, P<0.001). The total length of hospital stay was less than that before PERT intervention (12 (10, 14) d vs. 14 (11, 16) d, P=0.001). There was no statistical significance in the time from hospitalization to anticoagulant therapy, the length of ICU stay and hospitalization cost between the two groups (all P>0.05). (2) Clinical outcomes during hospitalization: There was no statistical significance in the incidence of hemorrhage and mortality between the two groups during hospitalization (both P>0.05). Conclusion:PERT has improved the efficiency of diagnosis and treatment of patients with acute pulmonary embolism and significantly shortened the total hospital stay, but its impact on clinical outcomes still needs further study.

Objective To explore the correlation of MPV,NLR,PT,APTT and FIB with early pro-gression of ACI in patients with BAD.Methods A total of 303 ACI patients with BAD admitted in our department of neurology from October 2021 to September 2023 were consecutively recrui-ted,and according to their progression within 7 d of onset,they were divided into progression group(89 cases)and un-progression group(214 cases).The general clinical data,blood routine re-lated indicators(MPV,NLR)and coagulation related indicators(PT,APTT,FIB)were compared between the two groups.Multivariate logistic regression analysis was applied to identify the rela-tionship of above indicators with early progression of ACI in BAD patients.ROC curve was plot-ted to analyze the predictive value of the indictors for disease progression in these patients.Results The progression group had significantly advanced age,larger proportions of diabetes,hyperlipi-demia and stroke history,and increased levels of uric acid,LDL-C,homocysteine,MPV,platelet distribution width,NLR,D-dimer and FIB,and shorter TT,PT and APTT when compared with the un-progressed group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that MPV,NLR,PT,APTT,and FIB were all independent influencing factors for early disease pro-gression of ACI in patients with BAD(P＜0.05,P＜0.01).ROC curve indicated that the AUC value of combined MPV,NLR,PT,APTT and FIB in detecting early disease progression was 0.859(95％CI:0.813-0.905).Conclusion Blood routine(MPV,NLR)and coagulation related indicators(PT,APTT,FIB)are closely associated with the early disease progression of ACI in BAD patients,and these indicators are of high value in predicting the early disease progression.

AIM To study the phenylpropanoids from Brandisia hancei Hook.f.and their antioxidant activities.METHODS The extract from B.hancei was isolated and purified by Rp-C18,MCI,semi-preparative HPLC,silica gel and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The cytotoxicities was determined by MTT method,and the antioxidant activities were determined by DPPH and ABTS+free radical scavenging methods.RESULTS Fifteen phenylpropanoids were isolated and identified as(+)-pinonesinol(1),(-)-medioresinol(2),(-)-syringaresinol(3),buddlenol D(4),(7R,7'R,7″S,8S,8'S,8″S)-4',5″-dihydroxy-3,5,3',4″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol(5),(-)-(7R,7'R,7″R,8S,8'S,8″S)-4',4″-dihydroxy-3,3',3″,5-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineolignan-7″,9″-diol(6),hedyotol A(7),dracunculifoside R(8),acteoside(9),isoacteoside(10),arenarioside(11),isomartynoside(12),curcasinlignan B(13),erythro-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-l-ol(14),citrusin C(15).Compounds 1-4 and 9-10 had no obvious cytotoxicity to HepG2 hepatoma cells.Compounds 1,3,9,10 and 12 had strong scavenging activities against DPPH radicals.Compounds 1-3,9-10,12 and 14 showed strong scavenging activities against ABTS+radical.CONCLUSION Compounds 1-8 and 12-15 are isolated from genus Brandisia for the first time.The phenylpropanoids from B.hancei show strong antioxidant activities.