Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20～25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.

Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22～25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.

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 observe the difference of bone micro-structure in different regions of proximal femur,micro-CT scanning was performed on 30 proximal femur specimens to explain the mechanism of proximal femur fracture and to provide anatomical basis for prosthesis design.Methods Totally 30 intact proximal femur specimens were obtained from 60-80 year-old cadavers.Micro-CT scanning was used to measure the trabecular thickness(Tb.Th),trabecular number(Tb.N),trabecular space(Tb.Sp),connectivity(Conn)and bone mineral density(BMD)and other parameters in 7 regions of proximal femur,including proximal pressure trabecular(PPT),distal pressure trabecular(DPT),femoral head-neck junction(FHNJ),head and neck of femoral neck(HNFN),the base of femoral neck(BPFN),intertrochanteric line(IL)and greater trochanter(GT).Results The bone mineral density of IL and GT were higher than those of BPFN,FHNJ,DPT and PPT.The trabecular thickness of GT was the largest,followed by IL,BPFN and HNFN,and the smallest was FHNJ,DPT and PPT.The trabecular space of IL was larger than that of GT,and the data of both were larger than those of other parts,among which DPT and PPT were the smallest.The trabecular number of IL and GT were the smallest,BPFN,HNFN and FHNJ were larger,and DPT was the largest.The volume fraction of IL was the smallest,BPFN and HNFN were larger,DPT and PPT were the largest.Conclusion The bone density,trabecular thickness,bone volume,and total volume of GT and IL in the proximal femur of elderly patients are all relatively large,so the reason for the high incidence of fractures is not due to weak internal bone microstructure;The bone density,trabecular thickness,and trabecular gap at the proximal and distal ends of the vertical trabecular bone are relatively small.If it is necessary to perform core decompression for prosthesis filling at this location,the design should be conducive to the mechanical conduction of the prosthesis and the regeneration of surrounding bone tissue.

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.

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.

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 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.

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.