Objective To investigate the effect of4-amino-2-trifluoromethyl-phenyl retinate(ATPR)on acute liver injury induced by lipopolysaccharide(LPS)in C57BL/6 mice and its related mechanism.Methods Fifteen 6-week-old male C57BL/6 strain mice were randomly divided into normal group,model group and ATPR group,with 5 mice in each group.Mice in the ATPR group were intraperitoneally injected with ATPR(15 mg/kg·d),and normal group and model group were given solvent.After continuous administration for one week,model group and ATPR group were intraperitoneally injected with LPS(6 mg/kg),and all mice were sacrificed 6 hours later.The contents of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in serum of mice were detec-ted.The mRNA levels of Interleukin-6(IL-6)and Tumor necrosis factor-alpha(TNF-α)were detected by qPCR.Hematoxylin-eosin(H&E)staining was used to observe the histopathological changes of liver in mice.The ultra-structural changes of mouse hepatocytes were observed by Transmission electron microscope(TEM).The expres-sion levels of mitochondrial damage-related proteins FUNDC1 and OPA1 and autophagy related proteins LC3B,P62,Beclin1 and ATG5 were detected by Western blot.Results Compared with the normal group,the content of ALT and AST in serum and the mRNA levels of IL-6 and TNF-α in liver tissue increased in the model group,and the changes were reversed in the ATPR group.H&E staining showed that the hepatic lobule structure was normal in the normal group,the hepatic cords were arranged radially,there was no hyperemia and inflammatory cell infiltra-tion,and the hepatocyte boundary was clear.In the model group,the intercellular space of liver was enlarged,the arrangement of hepatic cords was disordered,and inflammatory cells infiltrated.In the ATPR group,the intercellu-lar space of liver and the structure of hepatic cords were restored,and the inflammatory cell infiltration was less.TEM showed that the damaged mitochondria and lipid droplet accumulation in the hepatocytes of mice in the model group were compared with that in the normal group,and the morphology and quantity of mitochondria and lipid droplet in the hepatocytes of mice in the ATPR group tended to be normal.Western blot showed that compared with the normal group,the expression of FUNDC1 protein in the liver tissues of mice in the model group increased,the expression of OPA1 protein decreased,the ratio of LC3B Ⅱ to LC3B Ⅰ decreased,the expression of P62 protein in-creased,the expression of Beclin1 and ATG5 protein decreased,and the above changes were reversed in the ATPR group.Conclusion ATPR alleviates acute liver injury induced by lipopolysaccharide in mice by promoting autoph-agy.

Objective To investigate the effect of cysteine-rich acidic secretory protein-like protein 1(SPARCL1)on atherosclerosis(AS)plaque formation.Methods A case-control study design was used,394 patients with con-firmed AS were selected as the case group,and 394 healthy medical examiners matched for age and gender were se-lected as the control group.The expression level of serum SPARCL1 was determined by enzyme-linked immunosor-bent assay;immunohistochemistry was used to assess the expression level and localization of SPARCL1 protein in the AS plaque region,and the expression of SPARCL1 protein was also detected in the neutrophils and monocytes of peripheral blood of AS patients and normal controls;SPARCL1 overexpressing and the recombinant adenoviral vec-tors were constructed to inhibit SPARCL1 overexpression and expression,and the effects of SPARCL1 on cell mi-gration were observed in the cell scratch assay using mouse macrophage cells(J774A.1)as target cells.Results Serum SPARCL1 levels in the AS patient group were lower than those in the healthy group(P<0.05);high SPARCL1 expression was detected in AS plaques and was mainly expressed in the cytoplasm of foamy cells;SPARCL1 expression levels in peripheral blood neutrophils and monocytes were lower than those in normal controls in AS patients(P<0.05);recombinant SPARCL1 overexpression and inhibition of expression of adenovirus was successfully constructed;the cell migration rate was decreased in J774A.1 cells that inhibited SPARCL1 expression and increased in J774A.1 cells that overexpressed SPARCL1(P<0.05).Conclusion SPARCL1 is highly ex-pressed in foam cells at the site of AS lesions,which may result from compensatory recruitment of peripheral blood monocytes and neutrophils,and SPARCL1 may be involved as a protective factors for blood vessels in inhibiting the development of AS plaques.

Objective:To construct a classification management model of medical equipment in public hospitals based on association rules algorithm,and to analyze its application effect in hospital equipment management.Methods:Equipment classification management was performed based on Apriori algorithm(association rule analysis)and K-means algorithm(equipment abnormal information mining)in the association rules algorithm,the classification management model of medical equipment in public hospitals was constructed to mine the abnormal characteristics of equipment status.A total of 244 medical devices in clinical use in Beijing Huilongguan Hospital from 2022 to 2023 were selected.According to the application of the classification management model of medical equipment in public hospitals based on the association rule algorithm,the equipment use period from January to December 2022 was set before the application of the association rule algorithm model,and the equipment use period from January to December 2023 was set to the time after the application of the association rule algorithm model.The scores of equipment classification management,the failure rate of different types of equipment and equipment efficiency score before and after the application of association rule algorithm model were compared.Results:After the application of association rule algorithm model,the average scores of warehousing management,use management,maintenance management and scrap management were(89.65±4.65)points,(90.25±4.36)points,(87.69±3.12)points and(90.36±3.39)points,respectively,which were higher than before the application,the difference was statistically significant(t=17.866,14.671,18.128,19.479,P<0.05).After the application of association rule algorithm model,the number of medical image diagnostic and auxiliary equipment,health monitoring equipment,rehabilitation equipment and intervention and treatment equipment that failed was 2,3,2,and 3,and the failure rates were 3.33%,4.69%,2.86%and 6.00%,respectively,which were lower than those before the application,the difference was statistically significant(x2=5.925,6.117,7.937,5.316,P<0.05).After the application of association rule algorithm model,the average scores of overall utilization efficiency,quality stability efficiency and accurate diagnosis and treatment efficiency of the equipment were(96.39±3.69)points,(94.23±3.06)points and(95.47±4.36)points,respectively,which were higher than those before the application,and the difference was statistically significant(t=16.762,17.919,11.769,P<0.05).Conclusion:The application of the classification management model of medical equipment in public hospitals based on association rules algorithm can realize the classification management of medical equipment in hospitals,improve the operating efficiency and management level of equipment,and reduce the equipment failure rate.

Objective : Cas9-RNP biomimetic nanoparticles cas9-RNP@ MMs were prepared by encapsulating the Cas9 Ribonucleoprotein complex (RNP) using mouse macrophage membranes，with the aim of utilizing this biomimetic nanoparticle to deliver the Cas9-RNP complex for gene editing ，and further study the endocytosis of Cas9- RNP@ MMs and its gene editing effect in mouse macrophage RAW264. 7 in vitro ，providing evidence for the development oflow-toxicity biomimetic nanoparticle carriers that inhibit NLRP3 therapeutic targets． Methods : The purified mouse macrophage membrane was mixed with the prepared cas9-RNP mixture，and after ultrasound，the CAS9- RNP@ MMS was obtained by liposome extrusion instrument ; The particle size of Cas9-RNP@ MMswas measured by nanoparticle tracking analysis，and the particle morphology of Cas9-RNP@ MMs was observed under transmission electron microscope．Laser confocal Fluorescence microscope imaging was used to analyze the endocytosis Cas9-RNP @ MMs．The Biocompatibility of Cas9-RNP@ MMs was measured by MTT assay．The expression of NLRP3 was detected by qPCR and Western blot to verify the knockdown effect of Cas9-RNP@ MMs on NLRP3 gene. Results: The average particle diameter of Cas9-RNP@ MMs prepared from macrophages was about 216 nm．Under laser confocal fluorescence microscope，the Cas9-RNP@ MMs could be successfully endocysed by Raw246. 7 cell．MTT assay indicated that the Cas9-RNP@ MMs-treated mouse macrophage RAW246. 7 had good biocompatibility．qPCR and Western blot showed that two NLRP3-specific guide RNA were mediated by Cas9-RNP@ MMs，with good effect of knockdown NLRP3 gene expression． Conclusion Nano-scale vesicles Cas9-RNP@ MMs loaded with Cas9-RNP complexes were successfully prepared by biomimetic nanoparticles． Cas9-RNP@ MMs have good biocompatibility and can be efficiently endocytosed by RAW246. 7 cells．Cas9-RNP@ MMs containing NLRP3-specific sgRNA can specifically knock down NLRP3 gene expression.

Objective : To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on lipopolysaccharide (LPS) -induced acute myocardial injury in C57BL/6 mice． Methods : Male mice of C57BL/6 strain were randomly divided into normal group，model group，ATRA group，and ferrostatin-1 group．Mice in the ATRA group were injected intraperitoneally with ATRA 15mg / (kg · d) ，ferrostatin-1 group received ferrostatin-1 2 mg / ( kg · d) ，the normal group and the model group were given solvent．After one week of continuous administration，the model group，ATRA group ，and ferrostatin-1 group were intraperitoneally injected with LPS 6 mg / kg． All mice were sacrificed after 6 hours．The contents of malondialdehyde ( MDA) and glutathione ( GSH) in serum of mice were detected． qPCR was used to detect mRNA levels of interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha (TNF-α) in heart tissue．Hematoxylin-eosin ( HE) staining was used to observe the changes of heart tissue in mice．Transmission electron microscopy (TEM) was used to observe the structure of mouse myocardial mitochondria．Western blot was used to detect the expression of ferroptosis markers glutathione peroxidase 4 ( GPX4) ，ferritin heavy chain 1 ( FTH1 ) ，Solute carrier family 7 member 11 ( SLC7A11 ) ，acyl-CoA synthetase long-chain family member 4 (ACSL4) and related regulatory proteins，Nuclear factor erythroid 2-related factor 2 ( NRF2 ) ，kelchlike ECH-associated protein 1 (KEAP1) . Results: Compared with the normal group，the MDA content in the serum of the model group increased and the GSH content decreased，the above changes were reversed in the ATRA group as well as in the ferrostatin-1 group．Compared with normal group，the mRNA levels of IL-6 and TNF-α in the heart tissue of model group increased steeply，the above changes were relieved in the ATRA group and the ferrostatin-1 group．There was no significant difference in HE staining of myocardial tissue among the groups of mice. Compared with the normal group，myocardial mitochondria in the model group showed the phenomenon of cristaereduction or disappearance under TEM，while myocardial mitochondrial injury was alleviated in the ATRA group and the ferrostatin-1 group．Western blot showed that GPX4，FTH1，SLC7A11，and NRF2 expression were reduced in the myocardial tissue of mice in the model group compared with the normal group，ACSL4 and KEAP1 expression increased．The above changes were reversed in the ATRA group as well as in the ferrostatin-1 group． Conclusion ATRA alleviates lipopolysaccharide-induced acute myocardial injury in mice by inhibiting ferroptosis.

Objective: To solve the problems of low throughput of current cell migration research methods，which was difficult to establish a stable concentration gradient and observe cell migration behavior in real time，a six-channel array microfluidic chip was designed in this paper． Methods : In this paper，a six-channel array microfluidic chip is designed．Firstly，multiphysics modeling and numerical simulation were performed using the finite element analysis software COMSOL Multiphysics 5．5 to analyze the flow behavior of the main pipeline of cell migration. Then，the throughput advantage of the device was verified by testing the chemotaxis response of healthy human neutrophils to different types of chemokine gradients in this microfluidic chip．Subsequently，by analyzing the migration rate of neutrophils in 6 patients with type II diabetes mellitus and 3 healthy people，the clinical applicability of the annular six-channel array microfluidic chip was further verified．Finally，the Pearson coefficient was used to analyze the correlation between neutrophil chemotaxis function and some physiological indicators in patients with diabetes. Results: The concentration gradient data inside the pipeline simulated by the simulation software was compatible with the real-time fluorescence test data of the pipeline．The average migration rate of healthy human neutrophils was (0．21 ± 0．01 ) μm / s in 100 nmol / L interleukin-8 ( IL-8 ) environment and (0．22 ± 0．01 ) μm / s in 100 nmol / L N-Formyl-Met-Leu-Phe ( fMLP) environment． In the comparison of neutrophil migration experiments between healthy people and diabetic patients，the chemotaxis rate of neutrophils in healthy people was (0．19 ± 0．01) μm / s ，and the neutrophil chemotaxis rate in diabetic patients was (0. 15 ± 0. 02 ) μm / s． Correlation analysis showed that neutrophil migration rate in patients with type II diabetes mellitus was inversely correlated with glycated hemoglobin． Conclusion The high-throughput microfluidic chip proposed in this paper allowed rapid and selective detection of cell migration characteristics at the single-cell level，and it could be used as a new tool for cell migration research.

Objective: To investigate the expression of secreted protein acidic and rich in cysteine⁃like 1 (SPARCL1) in atherosclerosis (AS) and the association between SPARCL1 gene rs7695558 and rs1049539 polymorphism with the susceptibility to AS. Methods : In this case⁃control study ,209 AS patients were selected as the case group , and 208 healthy matched in age and sex were selected as the control group. The expression level of serum SPARCL1 was measured by enzyme⁃linked immunosorbent assay (ELISA) . Linear and Logistic regression analysis were used to evaluate the correlation between SPARCL1 level and vascular risk factors , lifestyle and demographic variables. Expression of SPARCL1 in tissue specimens was assessed by immunohistochemistry. Single nucleotide polymorphisms (SNPs) were genotyped by high resolution melting method. Chi⁃square test was used to analyze the relationship between rs7695558 and rs1049539 polymorphism and susceptibility to AS. Results: The serum expression level of SPARCL1 in AS patients was lower than that in healthy controls (Z = - 2. 916 ,P = 0. 004) . The level of SPARCL1 was related to age (P = 0. 027) and diastolic blood pressure ( P = 0. 008) , but not to sex and other cardiovascular risk factors (P > 0. 05) . The expression level of SPARCL1 in atherosclerotic lesions of coronary artery tissue increased. There was no significant difference in gene distribution of rs7695558 and rs1049539 between the case group and the control group by chi⁃square test (P > 0. 05) . In the recessive genetic model of rs7695558 , there was a difference in the distribution of genes with and without A. Patients without A allele (GG) had a lower risk of AS than patients with A allele (AA + AG) . The OR value was 0. 417 ,95% CI :0. 184 ~ 0. 945 , which was significant at 10% confidence level ( P = 0. 034) . Conclusion Rs7695558 , a new susceptible site related to AS risk , located in the intron of human SPARCL1 gene is identified for the first time in Anhui population of China , suggesting that SPARCL1 may play an anti⁃AS role as a vascular protective factor.

Objective:To evaluate the effect of blunt separation method on peripherally inserted central venous catheters.Methods:The randomized controlled trials regard to the effect of blunt separation method on peripheral central venous catheters were retrieved from CNKI, Wan fang Data Knowledge Service Platform, CQVIP, CBM, Cochrane, PubMed, EMBASE and Web of science from January 2010 to March 2021, two researchers performed quality assessments and extracted data according to Cochrane evaluation manual standards. RevMan 5. 4 software was used for statistical analysis.Results:A total of 11 randomized controlled trials were analyzed, including 1379 participants. The meta-analysis results showed that there was no statistical difference in the successful rate of one-time sheath delivery ( OR=1.62, 95% CI 0.92-2.86, P>0.05). However, patients in blunt separation group showed lower blood loss ( OR=0.24, 95% CI 0.11-0.50, P<0.05), lower the incidence of seepage at puncture site ( OR=0.18, 95% CI 0.09-0.37, P<0.05) than those in traditional skin expansion group at 24h after catheterization, and less the time of maintenance within 7 days after catheterization ( MD=-0.95, 95% CI-1.78--0.11, respectively, P<0.05). Conclusions:Blunt separation method can significantly reduce the incidence of complications and the time of catheter maintenance. Due to the limited quality of included studies, more high quality studies are needed to verify the conclusions.

Objective: To explore the effect of melatonin(MLT) on human umbilical vein endothelial cell(HUVEC) injury induced by high glucose and to explore its probable molecular mechanism. Methods: HUVEC were cultured and divided into three groups: control group, model group and treatment group. The control group(Ctrl group) was treated with DMEM medium at a normal low glucose level(5.5 mmol/L glucose), and the model group(HG group) was treated with DMEM medium at a high glucose level(30 mmol/L glucose). Treatment group(HG+MLT group) was treated with DMEM medium at a high glucose level containing 100 μmol/L melatonin. The method of MTT was used to detect the effects of high glucose and melatonin on HUVEC proliferation. The release of lactate dehydrogenase(LDH) in cell culture supernatant was determined. The production of reactive oxygen species(ROS) was detected by flow cytometry. Hoechst 33342/PI double-staining was used to detect cell apoptosis and necrosis. Western blot was used to detect the effects of high glucose and melatonin on endoplasmic reticulum stress and cell pyroptosis related protein expression in HUVEC. Results: Compared with the control group, cell proliferation level of the model group decreased, LDH releasing in cell culture supernatant increased, ROS production increased, the blue and red fluorescence increased in the double-staining, the expressions of GRP78, ATF4, CHOP, IRE1α, PERK, ATF6α, NLRP3, cleaved caspase-1, IL-1β increased. Compared with model group, cell proliferation level of the treatment group increased, LDH releasing in cell culture supernatant decreased, ROS production decreased, the blue and red fluorescence decreased in the double-staining, the expressions of GRP78, ATF4, CHOP, IRE1α, PERK, ATF6α, NLRP3, cleaved caspase-1, IL-1β decreased. Conclusion MLT can alleviate HUVEC damage induced by high glucose, and the probable mechanism may be related to the regulation of endoplasmic reticulum stress and cell pyroptosis.

MicroRNAs(miRNAs)are trans-acting small regulatory RNAs that work coordinately with transcription factors(TFs)to shape the repertoire of cellular mRNAs available for translation.Despite our growing knowledge of individual plant miRNAs,their global roles in gene regulatory networks remain mostly unassessed.Based on interactions obtained from public databases and curated from the literature,we reconstructed an integrated miRNA network in Arabidopsis that includes 66 core TFs,318 miRNAs,and 1712 downstream genes.We found that miRNAs occupy distinct niches and enrich miRNA-containing feed-forward loops(FFLs),particularly those with miRNAs as intermediate nodes.Further analyses revealed that miRNA-containing FFLs coordi-nate TFs located in different hierarchical layers and that intertwined miRNA-containing FFLs are associated with party and date miRNA hubs.Using the date hub MIR858A as an example,we performed detailed molecular and genetic analyses of three interconnected miRNA-containing FFLs.These analyses revealed individual functions of the selected miRNA-containing FFLs and elucidated how the date hub miRNA fulfills multiple regulatory roles.Collectively,our findings highlight the prevalence and importance of miRNA-containing FFLs,and provide new insights into the design principles and control logics of miRNA regulatory networks governing gene expression programs in plants.