BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.

BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Rats ; Animals ; Urinary Bladder Neck Obstruction/pathology* ; Survivin/genetics* ; Urinary Bladder/pathology* ; Fibrosis

Objective To investigate the protective effect of Gui Zhi Fuling Jiaonang on endurance to ischemia and hypoxia .Methods Mice were randomized into four groups :control group ,positive drug control group ,Gui Zhi Fuling Jiaonang high‐dose group (0 .93 g/kg) ,and Gui Zhi Fuling Jiaonang low‐dose group (0 .465 g/kg) . All mice were treated with corresponding drugs for 7 days .The hypoxia mice model was established through hypoxia in the closed jars , cerebral anoxia by decapitation , poisoning with sodium nitrite and isoprenaline . Then the hypoxia‐ischemia rat model was established by injecting isoproterenol . The anti‐hypoxic effects were observed . Results Compared with control group ,Gui Zhi Fuling Jiaonang high‐dose group (0 .93 g/kg) had a tendency to extend the survival time of mice model established through hypoxia in the closed jars ;Gui Zhi Fuling Jiaonang high‐dose (0 .93 g/kg) and low‐dose (0 .465 g/kg) groups had a tendency to extend the survival time of mice model established through cerebral anoxia by decapitation (P>0 .05) .Compared with that in control group ,the survival time of mice in Gui Zhi Fuling Jiaonang low‐dose group under poisoning with sodium nitrite and Gui Zhi Fuling Jiaonang high‐dose group under poisoning with isoprenaline were significantly prolonged .Besides ,Gui Zhi Fuling Jiaonang relieved myocardial tissue damage caused by ischemia and hypoxia ( P< 0 .05 ) .Conclusion Gui Zhi Fuling Jiaonang has an obviously protective effect on isoprenaline‐induced hypoxia and myocardial ischemia .

This paper discusses the recognition of heart sound for evaluating the cardiac contractility change trend, which includes heart sound samples recorded at different exercise condition. Especially, focused on the recognition of heart sound recorded after high intensity exercise workload. The algorithm proposed consisted of two correlative methods. The first was to recognize heart sound recorded at rest and after low intensity exercise workloads by probabilistic neural network and the second was to recognize heart sound recorded after high intensity exercise workloads based on the characteristic of heart sound. Both methods have two consecutive phases. Firstly, all peaks, including the peaks of both heart sounds and noise, are marked by a repetitive threshold detecting algorithm. Secondly, probabilistic neural network is employed to classify the peaks detected in the first phase into Si, S2, and noise. Finally, the performance of the algorithm was evaluated using 45 digital heart sound recordings including normal and abnormal heart sound, which were recorded at rest and after low intensity exercise workloads, and 28 digital heart sound recordings recorded after high intensity exercise workloads. The results showed that over 94% of heart sound samples were classified and recognized correctly. Moreover, the reasons for the wrong classification, of which omitting and misdetection are two main problems, are also discussed and solutions are proposed. So this method can be improved and refined in following studies. In conclusion, this algorithm is a reliable approach to detect and classify heart sounds, providing a solid basis for further heart sound analysis.
Algorithms ; Heart Sounds ; physiology ; Humans ; Neural Networks (Computer) ; Phonocardiography ; Signal Processing, Computer-Assisted

Wavelet transform is internationally recognized a good tool for time-frequency analysis. This paper presents a novel speckle suppression method for medical B-Scan images. The speckle is produced by scattering echoed signals in different phases because of wave interference. The software MATLAB is used as operating platform meanwhile the wavelet is used to eliminate the noise. The ultrasound image is processed by adaptive method and then the selected sym8 wavelet is used in the multiresolution analysis of the ultrasound image. The result shows that this method can effectively reduce the speckle noise.