Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

Objective To establish a reliable Pseudomonas aeruginosa(PA)-induced sepsis model,providing an effective experimental method for investigating the pathogenicity,antibiotic resistance mechanism and infection-related inflammatory pathways of PA.Methods PA ATCC 27853 was selected as experimental strain.Different concentrations of bacterial suspension were applied to the surface of erector spinae muscle in mice.Echocardiography was performed 24 h after infection to examine cardiac function.Heart,lung,kidney tissue and blood samples were collected.Serum creatinine(Cr),blood urea nitrogen(BUN),inflammatory factors,and cardiac troponin Ⅰ(CTNI)were detected.The pathological changes in the heart,lung,and kidney tissues were observed.Results The survival rates of the 107 CFU/mL group,108 CFU/mL,109 CFU/mL,and 1010 CFU/mL groups were 100%,93.3%,73.3%,and 26.7%,respectively.The concentration of interleukin-6(IL-6)in the PA-infected group was significantly higher than that in the non-infected group.The concentration of tumor necrosis factor-α(TNF-α)in 108 CFU/mL group and 109 CFU/mL group were significantly higher than that in the non-infected group.The left ventricular ejection fraction(LVEF)of 108 CFU/mL and 109 CFU/mL groups decreased significantly compared to the non-infected group,and the CTNI level increased significantly in infected group compared to the non-infected group.Compared with the non-infected group,only the 109 CFU/mL group showed significant statistical differences in Cr and BUN levels,while no significant differences were observed in the other PA-infected groups.The results of histopathology showed that the heart,lung,and kidney tissues of mice in the 109 CFU/mL group were significantly infiltrated by inflammatory cells,with obvious edema of tissue cells,disordered structural arrangement,thickening of alveolar septa,and renal interstitial stenosis.Conclusion The experiment successfully established a sepsis model induced by PA with a bacterial concentration of 109 CFU/mL,which is stable and reliable,and can provide a model basis for exploring sepsis and PA infection diseases.

Cilia,as cellular sensory organelles,actively partici-pate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mecha-nism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activa-ting cellular autophagy and how autophagy regulates cilia genera-tion and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely asso-ciated with the clinical manifestations and pathogenesis of vari-ous ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small mole-cule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundw-ork for developing highly specific targeted small molecule inhibi-tors of ciliogenesis and for the treatment of ciliopathies and canc-ers.By systematically discussing ciliogenesis,autophagy,disea-ses and drugs,this review offers new insights for further elucida-ting the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and de-veloping therapeutic strategies in the future.

Objective To investigate the biological function of the proprotein convertase subtilisin/kexin type 9(PCSK9)in prostate cancer(PCa)and its effect on ferroptosis sensitivity Methods Bioinformatics was used to analyze the relationship between the expression of PCSK9 and the prognosis of prostate cancer.The expression of PCSK9 in PCa cell lines were detected using RT-qPCR.PCa cells with PCSK9 knockdown were constructed using siRNA,and the The effect of PCSK9 on cell proliferation,migration,and invasion were detected using CCK-8 assays and Transwell assays.The Cancer Therapeutics Response Portal(CTRP)was employed to investigate the correlation between PCSK9 and ferroptosis drug sensitivity,and PCa cells with PCSK9 knockdown were treated with the ferroptosis inducer(RSL3)to detect the sensitivity to ferroptosis.Results Bioinformatics showed low expression of PCSK9 had longer disease specific survival(P<0.05).The results of the in vitro experiments showed that PCSK9 knockdown significantly inhibited the proliferation,migration,and invasion of PCa cells(P<0.001).Furthermore,CTRP analysis showed that cellular sensitivity to ferroptosis inducers correlated with the expression level of PCSK9.PCSK9 knockdown cells exhibited higher sensitivity to the ferroptosis inducer RSL3.Conclusion Knockdown of PCSK9 inhibits the proliferation,migration,and invasion of PCa cells,and increases the sensitivity of cells to ferroptosis inducers.PCSK9 may provide new insights for the treatment of PCa.

Objective To investigate the biological function of the proprotein convertase subtilisin/kexin type 9(PCSK9)in prostate cancer(PCa)and its effect on ferroptosis sensitivity Methods Bioinformatics was used to analyze the relationship between the expression of PCSK9 and the prognosis of prostate cancer.The expression of PCSK9 in PCa cell lines were detected using RT-qPCR.PCa cells with PCSK9 knockdown were constructed using siRNA,and the The effect of PCSK9 on cell proliferation,migration,and invasion were detected using CCK-8 assays and Transwell assays.The Cancer Therapeutics Response Portal(CTRP)was employed to investigate the correlation between PCSK9 and ferroptosis drug sensitivity,and PCa cells with PCSK9 knockdown were treated with the ferroptosis inducer(RSL3)to detect the sensitivity to ferroptosis.Results Bioinformatics showed low expression of PCSK9 had longer disease specific survival(P<0.05).The results of the in vitro experiments showed that PCSK9 knockdown significantly inhibited the proliferation,migration,and invasion of PCa cells(P<0.001).Furthermore,CTRP analysis showed that cellular sensitivity to ferroptosis inducers correlated with the expression level of PCSK9.PCSK9 knockdown cells exhibited higher sensitivity to the ferroptosis inducer RSL3.Conclusion Knockdown of PCSK9 inhibits the proliferation,migration,and invasion of PCa cells,and increases the sensitivity of cells to ferroptosis inducers.PCSK9 may provide new insights for the treatment of PCa.

Objective:To explore the effects of miR-125b on the proliferation, invasion and migration of pancreatic cancer cells by targeting SMYD2 signaling pathway.Methods:The expression of miRNA-125b in Aspc-1 and BxPC-3 lines of pancreatic cancer cells were detected. miRDB, ENCORI and TargetScan databases were used to predict the potential target genes of miRNA-125b. The downstream target genes of miRNA-125b were identified by qPCR assay and double luciferase reporter gene assay. Western blot analysis was performed to detect SMYD2 protein expression after transfection with miRNA-125b inhibitor. EdU staining, Annexin V-FITC/PI assay and Annexin V-FITC/PI assay were used to detect the effects of miRNA-125b inhibitor transfection and simultaneous transfection of miRNA-125b and SMYD2 inhibitor on cell proliferation, clonogenesis and apoptosis.Results:The expression level of miRNA-125b in pancreatic cancer cell lines was higher than that in normal pancreatic duct cells ( P<0.05). The downstream target gene of miRNA-125b was identified as SMYD2 by qPCR assay and double luciferase reporter gene assay. The expression of SMYD2 protein in miR-125b inhibitor group was higher than that in NC group ( P<0.01). EdU cell proliferation assay showed that the number of miRNA-125b positive cells in inhibitor group was lower than that in NC group and Inhibitor NC group ( P<0.05). The number of clones in miR-125b inhibitor+si-SMYD2 group was more than that in miR-125b inhibitor group ( P<0.01). Annexin V-FITC/PI assay showed that the apoptosis number of cell cells in miR-125b inhibitor+si-SMYD2 group was lower than that in miR-125b inhibitor group ( P<0.01) . Conclusion:miRNA-125b is highly expressed in pancreatic cancer cells, and can directly affect the expression of SMYD2 gene, thereby promoting the proliferation and inhibiting the apoptosis of pancreatic cancer cells.

Porcine arthritis,one of the common chronic diseases in large-scale pig farms,can signifi-cantly reduce the production performance of meat pigs.In this study,a strain of Haemophilus pa-rasuis(HPS)was isolated from the joint fluid of a lame pig.The HPS was analyzed in terms of se-rotypes,virulence genes,and resistance genes.Additionally,it was treated with sensitive antibiotics to provide a theoretical basis for the comprehensive prevention and treatment of arthritis in meat pigs in future production settings.A strain of HPS type 14 was isolated from the joint fluid of dis-eased pigs.The HPS isolate demonstrated sensitivity to β-lactams and tetracyclines,while florfeni-col and polymyxin effectively inhibited its growth at low concentrations.However,the bacteria ex-hibited resistance to sulfonamides and ciprofloxacin.The treatment of affected pigs with clinical ar-thritis using doxycycline and enrofloxacin injections proved effective.Compared to the infected group,in which the sick pigs experienced difficulty flexing their carpal and tarsal joints and exhibi-ted significant lameness,the pigs in the treatment group showed marked improvement.Their joints were only slightly swollen,and the clinical symptoms of arthropathy were alleviated.

Objective To evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets using hydroxyethyl starch(HES)130/0.4 sodium chloride injection as an extraction medium.Methods Firstly,40 Sprague Dawley(SD)rats including 20 male and 20 female ones were seleted and randomly enrolled into a sample group and a control group by sex,with 20 ones in each group.Secondly,instead of plasma HES 130/0.4 sodium chloride injection was used to leach disposable plasma virus-inactivated blood transfusion sets to prepare the test solution by simulating clinical application such as lighting,adsorption and filtration and storage.Finally,the test solution and HES 130/0.4 sodium chloride injection were injected into the tail vein of the SD rats at a dose of 20 mL/kg for 28 d in the sample group and in the control group respectively,and the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets and the feasibility of using HES 130/0.4 sodium chloride injection as the extraction medium to assess their subchronic systemic toxicity were evaluated with clinical observation,body mass monitoring,clinical pathology examination,gross necropsy and histopathology examination.Results The sample group and control group had no significant differences in mortality rates,clinical observation results,body mass,gross necropsy results,hematological and coagulation examination results and organ weight(all P>0.05);blood biochemical examinations showed the male rats in the sample group had the cholesterol(CHO)values higher while the creatinine(CR)values lower than those in the control group,with the differences being statistically significant(both P<0.05)and the two indexes within the range of the laboratory's historical reference data,and other blood biochemical indexes were not significantly different(all P>0.05);the sample group had the spleen weight-to-body mass ratios of the female rates lower significantly than those in the control group(P<0.05),and the ratios of other organ weight to body mass had significant differences(all P>0.05);histopathology examination showed slight pathological changes in liver,spleen and kidney of female rats and in spleen and kidney of male rats in the sample group,and the female and male rats in the control group had similar pathological changes found in the sample group,which might be caused by HES metabolites.Conclusion Disposable plasma virus-inactivated blood transfusion sets prove to have no significant subchronic systemic toxicity,and its feasible to use HES 130/0.4 sodium chloride injection as the extraction medium to evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets.[Chinese Medical Equipment Journal,2025,46(10):29-35]

Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

Objective:To explore the effects of miR-125b on the proliferation, invasion and migration of pancreatic cancer cells by targeting SMYD2 signaling pathway.Methods:The expression of miRNA-125b in Aspc-1 and BxPC-3 lines of pancreatic cancer cells were detected. miRDB, ENCORI and TargetScan databases were used to predict the potential target genes of miRNA-125b. The downstream target genes of miRNA-125b were identified by qPCR assay and double luciferase reporter gene assay. Western blot analysis was performed to detect SMYD2 protein expression after transfection with miRNA-125b inhibitor. EdU staining, Annexin V-FITC/PI assay and Annexin V-FITC/PI assay were used to detect the effects of miRNA-125b inhibitor transfection and simultaneous transfection of miRNA-125b and SMYD2 inhibitor on cell proliferation, clonogenesis and apoptosis.Results:The expression level of miRNA-125b in pancreatic cancer cell lines was higher than that in normal pancreatic duct cells ( P<0.05). The downstream target gene of miRNA-125b was identified as SMYD2 by qPCR assay and double luciferase reporter gene assay. The expression of SMYD2 protein in miR-125b inhibitor group was higher than that in NC group ( P<0.01). EdU cell proliferation assay showed that the number of miRNA-125b positive cells in inhibitor group was lower than that in NC group and Inhibitor NC group ( P<0.05). The number of clones in miR-125b inhibitor+si-SMYD2 group was more than that in miR-125b inhibitor group ( P<0.01). Annexin V-FITC/PI assay showed that the apoptosis number of cell cells in miR-125b inhibitor+si-SMYD2 group was lower than that in miR-125b inhibitor group ( P<0.01) . Conclusion:miRNA-125b is highly expressed in pancreatic cancer cells, and can directly affect the expression of SMYD2 gene, thereby promoting the proliferation and inhibiting the apoptosis of pancreatic cancer cells.