Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Image 1.

Objective To explore the effect and mechanism of long non-coding RNA (LncRNA) nuclear enriched abundant transcript 1 (NEAT1) on proliferation and metastasis of myeloma through miR-195-5p/CCAAT enhancer binding protein α (CEBPA) axis. Methods ① From March 2021 to February 2023,bone marrow mononuclear cells (BMNC) from 40 patients with multiple myeloma (MM) and 10 healthy bone marrow donors who were hospitalized in the Department of Hematology the Second People's Hospital of Liaocheng City,Shandong First Medical University and MM cell lines U266,RPMI 8226,NCI-H929 and MM.1S were collected. RT-qPCR and Western blot were used to detect NEAT1,miR-195-5p,CEBPA mRNA and protein levels in cells. ② U266 cells were divided into overexpressing NEAT1 group (NEAT1 group) and its control group (NC group),knockdown NEAT1 expression group (sh-NEAT1 group) and its control group (sh-NC group),overexpressing NEAT1 and miR-195-5p group (NEAT1+miR-195-5p group) and its control group (NEAT1+miR-NC group),and overexpressing miR-195-5p and CEBPA group (miR-195-5p+CEBPA group) and its control group (miR-195-5p+NC group). CCK-8 and EdU staining were used to detect cell proliferation ability. Transwell assay was used to detect cell migration and invasion ability. RT-qPCR was used to detect NEAT1,miR-195-5p,and CEBPA mRNA levels in cells. Western blot was used to detect CEBPA,Ki67,proliferating cell nuclear antigen (PCNA),matrix metalloproteinase (MMP)-2,MMP-9,phosphoinositide 3 kinase (PI3K),p-PI3K,protein kinase B (AKT),p-AKT,mechanistic target of rapamycin (mTOR),and p-mTOR protein levels. ③ Twenty nude mice were divided into knockdown NEAT1 expression group (sh-NEAT1 group) and its control group (sh-NC group),with ten mice in each group. Nude mice were subcutaneously injected with corresponding transfected U266 cell suspension,and the differences in various indicators of transplanted tumor were measured after 4 weeks. Results ① Compared with normal BMNC,NEAT1,CEBPA mRNA and protein levels in MM patients and MM cell lines were increased,while miR-195-5p level was decreased,and the differences were significant (t=11.697,9.272,4.352,11.639,all P<0.05). ② After overexpression of NEAT1,NEAT1,CEBPA mRNA and protein levels in cells were increased (t=12.825,5.874,13.893),while miR-195-5p level was decreased (t=4.797),the A value and EdU positive rate after 72 hours of cell culture were increased (t=9.425,5.632),the number of migration/invasion cells were increased (t=8.841,5.364),and Ki67,PCNA,MMP-2,MMP-9,p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR protein levels were increased (t=14.227,7.743,7.348,7.803,8.714,8.629,7.359),with significant differences (all P<0.05). After knockdown the expression of NEAT1,NEAT1,CEBPA mRNA and protein levels in cells were decreased (t=5.776,5.001,4.503),while miR-195-5p level was increased (t=4.456),the ability of cell proliferation,invasion and metastasis was decreased (t=6.204,8.792),with significant differences (all P<0.05). Overexpression of miR-195-5p could partially reverse the effects of overexpression of NEAT1 on the aforementioned cellular indicators,and the differences were significant (t=4.356～10.809,all P<0.05). Meanwhile,overexpression of CEBPA could partially reverse the effects of overexpression of miR-195-5p on the aforementioned cellular indicators,and the differences were significant (t=4.329～14.452,all P<0.05). ③ Knockdown NEAT1 expression could inhibit the growth of transplanted tumors in nude mice,and the differences were significant (t=5.175～18.190,all P<0.05). Conclusion LncRNA NEAT1 promotes proliferation,invasion and metastasis of MM cells by targeting miR-195-5p/CEBPA expression,which may act by activating the PI3K/AKT/mTOR pathway.

BACKGROUND:With the continuous progress of science and technology,the introduction of new technologies and methods will bring more possibilities and new breakthroughs for the application of shape memory alloys in the fields of assistive and rehabilitation. OBJECTIVE:To review the application status of shape memory alloys in assistive and rehabilitation equipment,discuss their main methods,techniques and results,summarize and put forward suggestions,hoping that shape memory alloys can be continuously optimized and bring more new changes for the development of assistive and rehabilitation equipment. METHODS:WanFang,PubMed,and Web of Science databases were searched by computer."Shape memory alloys,application progress,orthodontics,orthopedic,prosthesis,rehabilitation,properties,implantation,mechanical properties,nickel-titanium memory alloys,actuation"were used as Chinese search terms."Shape memory alloys,application,orthodontics,orthopedic,prosthetics,rehabilitation,properties,implant,drive,progress,prostheses"were used as English search terms.Finally,91 articles were included for review. RESULTS AND CONCLUSION:(1)Shape memory alloy has the characteristics of corrosion resistance,wear resistance,biocompatibility,fatigue resistance,kink resistance and other properties.Compared with other traditional materials(stainless steel,titanium alloy,cobalt-chromium alloy,etc.),shape memory alloy has lower elastic modulus and no biological toxicity,which is suitable for long-term implantation as an implant prosthesis.Due to its shape memory effect and excellent mechanical properties,it is mainly used as a driving element or as a bridge connecting the device and the human body in artificial limbs,orthoses and rehabilitation equipment.(2)The use of shape memory alloy drive elements can reduce the weight of the device,eliminate noise,easy to operate,easy to carry,better assist joint movement;compared with the use of pneumatic,hydraulic,and electrical drive methods of the device,it has obvious advantages.(3)In addition,shape memory alloy can produce permanent and stable stress during deformation.Compared with stainless steel,titanium alloy and aluminum alloy,shape memory alloy has a higher material recovery rate and does not need to be replaced and adjusted frequently,so it is more practical in the correction of deformity.(4)At present,shape memory alloy is most commonly used in orthosis,and the best clinical application effect is in stapes prosthesis.However,due to the limitations of technology and cost,shape memory alloys are rarely used in artificial limbs and rehabilitation equipment,and there is a lack of large sample size studies on the application effect.(5)Although shape memory alloys have been developed in the field of auxiliary and rehabilitation,there are still many problems:it is difficult to accurately control the shape memory alloys;the cooling speed of shape memory alloy is slow;the deformation speed of shape memory alloy cannot be controlled;there is a lack of comparative research and expert consensus on shape memory alloys with different properties;shape memory alloys are costly and expensive.(6)In the future,attention should be paid to the development of new shape memory alloys,increase comparative research,and use new technologies and methods(such as 4D printing)to solve the existing problems,so as to develop high-performance assistive devices and rehabilitation equipment.

Objective : To explore the risk factors of biliary stricture after liver transplantation and to construct a nomogram prediction model. Methods : The clinical data of 208 liver transplant recipients in hospital were retrospectively analyzed, including 54 cases in the biliary stricture group and 154 cases in the non-biliary stricture group. Multivariate Logistic regression analysis was used to screen out independent predictors, fit the prediction model and construct a visual nomogram to evaluate the prediction model. Survival curves were drawn and multivariate Cox regression analysis was performed. Results : Autoimmune liver diseases(OR=6.610,95%CI: 1.410-30.99), alanine aminotransferase(ALT)(OR=1.007,95%CI: 1.003-1.011), warm ischemia time(OR=1.972,95%CI: 1.399-2.780), cold ischemia time(OR=1.016,95%CI: 1.010-1.022), cytomegalovirus infection(OR=6.037,95%CI: 1.480-24.63) and hepatic vascular stenosis(OR=7.784,95%CI: 2.312-26.20) were independent predictors of biliary stricture after liver transplantation. The area under the curve(AUC) of the nomogram prediction model was 0.921, the cut-off value was 0.238, the sensitivity was 0.889, and the specificity was 0.838. The model showed good discrimination. The Brier score was 0.092, Hosmer-Lemeshow goodness-of-fit testP=0.253, Calibration curve(B=1 000) was in good agreement, and the model showed good calibration. Decision curve analysis(DCA) showed that the application of the model could benefit liver transplant recipients. The postoperative follow-up time was 27-60 months. The cumulative survival rate of the non-biliary stricture group was better than that of the biliary stricture group(P=0.019), but multivariate Cox regression analysis showed that biliary stricture(HR=1.194, 95%CI: 0.624-2.285) was not an independent risk factor for survival after liver transplantation. Conclusion The nomogram model based on autoimmune liver diseases, ALT, warm ischemia time, cold ischemia time, cytomegalovirus infection and hepatic vascular stenosis performs well and can be used to predict the occurrence of biliary stricture after liver transplantation.

Objective: To investigate the ferroptosis induced by sesamin in triple-negative breast cancer ( TNBC) 4T1 cells and its underlying mechanism . Methods: The binding energy of sesamin with glutathione peroxidase 4 (GPX4) , solute carrier family 7 member 11 ( SLC7A11) , and P53 was analyzed by molecular docking. Mouse TNBC cell line 4T1 was used as a model . Different concentrations of sesamin were administered to 4T1 cells . The effect of sesamin on cell viability was assessed using the cell counting kit 8 (CCK-8) . Transwell assay was used to evaluate the effect of sesamin on cell migration and invasion . The contents of Fe2 + , malondialdehyde (MDA) , and reduced glutathione (GSH) in the cells were measured using kits . 2 ′,7 ′-dichlorofluorescein diacetate (DCFH-DA) probe was employed to detect the content of reactive oxygen species (ROS) in cells . Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot were performed to evaluate the expression of GPX4 , SLC7A11 , and P53 at mRNA and protein levels . Results: The binding energies of sesamin with GPX4 , SLC7A11 and P53 were - 21 . 46 , - 21 . 67 , and - 27 . 03 kJ/mol , respectively . Compared with the control group , the viability of 4T1 cells in different concentrations of sesamin groups decreased gradually ( P < 0. 001) , and the migration and invasion ability of 4T1 cells in 20 , 40 , and 80 μmol/L sesamin groups decreased gradually (all P < 0. 001) . Compared with the control group , the contents of Fe2 + , MDA , and ROS in 4T1 cells of 20 , 40 , and 80 μmol/L sesamin groups increased , and the content of GSH decreased . Compared with the control group , the mRNA and protein expression of GPX4 and SLC7A11 in 4T1 cells in the sesamin treatment group decreased , and the mRNA and protein expression of P53 increased ( all P < 0. 001) . Conclusion Sesamin may induce the ferroptosis in 4T1 cells through P53/SLC7A11 /GPX4 pathway .

Objective To investigate the changes of macrophages and hemophagocytes in bone marrow smears of patients with multiple myeloma(MM)before and after chemotherapy and their correlation with clinical prognostic value.Methods A total of 300 MM patients treated in Liaocheng Second People's Hospital Affiliated to Shandong First Medical University from June 2018 to June 2023 were selected as the study objects.All patients received at least 3 courses of chemotherapy and were divided into the remission group(n=214)and the non-remission group(n=86)according to the clinical effect.Immunoglobulin(Ig)A,IgG,CD3+,CD4+,CD8+,interleukin(IL-2),IL-4,IL-6,IL-17,tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β,macrophages and hemophagocytes were detected in the two groups and compared between the two groups.COX regression was used to analyze the relationship between immunological indexes and non-remission of chemotherapy.The relationship between macrophages and hemophagocytes and non-remission of chemotherapy was analyzed by restricted cubic spline.The multiplicative interaction of macrophages and hemophagocytes on non-remission of chemotherapy was analyzed using an unconditioned Logistic regression model,and the additive interaction was analyzed using the interaction calculation table.Receiver operating characteristic(ROC)curve analysis of macrophages and hemophagocytes alone or in combination to determine the value of chemotherapy non-remission.Results The overall response rate(ORR)and non-response rate(NRR)of MM patients were 71.33%and 28.67%respectively.Compared with before treatment,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes were significantly decreased in both groups after treatment(tslow=9.252～61.177,tnot slow=4.057～35.797).CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly increased(tslow=9.706～33.940,tnot slow=4.227～16.167),and the differences were statistically significant(all P<0.05).After treatment,compared with the remission group,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes in the non-remission group were significantly higher than those in remission group(t=3.362～30.028),CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly lower than those in remission group(t=3.736～13.998).and the differences were statistically significant(all P＜0.05).After adjusting the influence of other factors by COX regression,the trend test of macrophages and hemophagocytes was still statistically significant the trend test of macrophages and hemophagocytes was still statistically significant(P<0.05).Patients with≥5 macrophages/tablet and≥3 hemophagocytes/tablet had a significantly increased risk of non-remission from chemotherapy(P<0.05).There were additive(OR=6.157,95%CI:3.768～12.978)and multiplicative(OR=5.648,95%CI:1.035～17.492)interactions between macrophages and hemophagocytes in the non-remission of chemotherapy.Compared with the single judgment of macrophages and hemophagocytes,the combination of the two has the highest accuracy in determining chemotherapy non-remission(P＜0.05).Conclusion Macrophages and hemophagocytic cells in MM patients after chemotherapy are significantly lower than those before chemotherapy,with≥5 macrophages/tablet and≥3 hemocyte phages/tablet,indicating that the risk of non-remission in patients with chemotherapy increased significantly,and the combination of the two can accurately judge the clinical efficacy.

Objective To investigate the changes of macrophages and hemophagocytes in bone marrow smears of patients with multiple myeloma(MM)before and after chemotherapy and their correlation with clinical prognostic value.Methods A total of 300 MM patients treated in Liaocheng Second People's Hospital Affiliated to Shandong First Medical University from June 2018 to June 2023 were selected as the study objects.All patients received at least 3 courses of chemotherapy and were divided into the remission group(n=214)and the non-remission group(n=86)according to the clinical effect.Immunoglobulin(Ig)A,IgG,CD3+,CD4+,CD8+,interleukin(IL-2),IL-4,IL-6,IL-17,tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β,macrophages and hemophagocytes were detected in the two groups and compared between the two groups.COX regression was used to analyze the relationship between immunological indexes and non-remission of chemotherapy.The relationship between macrophages and hemophagocytes and non-remission of chemotherapy was analyzed by restricted cubic spline.The multiplicative interaction of macrophages and hemophagocytes on non-remission of chemotherapy was analyzed using an unconditioned Logistic regression model,and the additive interaction was analyzed using the interaction calculation table.Receiver operating characteristic(ROC)curve analysis of macrophages and hemophagocytes alone or in combination to determine the value of chemotherapy non-remission.Results The overall response rate(ORR)and non-response rate(NRR)of MM patients were 71.33%and 28.67%respectively.Compared with before treatment,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes were significantly decreased in both groups after treatment(tslow=9.252～61.177,tnot slow=4.057～35.797).CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly increased(tslow=9.706～33.940,tnot slow=4.227～16.167),and the differences were statistically significant(all P<0.05).After treatment,compared with the remission group,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes in the non-remission group were significantly higher than those in remission group(t=3.362～30.028),CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly lower than those in remission group(t=3.736～13.998).and the differences were statistically significant(all P＜0.05).After adjusting the influence of other factors by COX regression,the trend test of macrophages and hemophagocytes was still statistically significant the trend test of macrophages and hemophagocytes was still statistically significant(P<0.05).Patients with≥5 macrophages/tablet and≥3 hemophagocytes/tablet had a significantly increased risk of non-remission from chemotherapy(P<0.05).There were additive(OR=6.157,95%CI:3.768～12.978)and multiplicative(OR=5.648,95%CI:1.035～17.492)interactions between macrophages and hemophagocytes in the non-remission of chemotherapy.Compared with the single judgment of macrophages and hemophagocytes,the combination of the two has the highest accuracy in determining chemotherapy non-remission(P＜0.05).Conclusion Macrophages and hemophagocytic cells in MM patients after chemotherapy are significantly lower than those before chemotherapy,with≥5 macrophages/tablet and≥3 hemocyte phages/tablet,indicating that the risk of non-remission in patients with chemotherapy increased significantly,and the combination of the two can accurately judge the clinical efficacy.

Objective To explore the effect and mechanism of long non-coding RNA (LncRNA) nuclear enriched abundant transcript 1 (NEAT1) on proliferation and metastasis of myeloma through miR-195-5p/CCAAT enhancer binding protein α (CEBPA) axis. Methods ① From March 2021 to February 2023,bone marrow mononuclear cells (BMNC) from 40 patients with multiple myeloma (MM) and 10 healthy bone marrow donors who were hospitalized in the Department of Hematology the Second People's Hospital of Liaocheng City,Shandong First Medical University and MM cell lines U266,RPMI 8226,NCI-H929 and MM.1S were collected. RT-qPCR and Western blot were used to detect NEAT1,miR-195-5p,CEBPA mRNA and protein levels in cells. ② U266 cells were divided into overexpressing NEAT1 group (NEAT1 group) and its control group (NC group),knockdown NEAT1 expression group (sh-NEAT1 group) and its control group (sh-NC group),overexpressing NEAT1 and miR-195-5p group (NEAT1+miR-195-5p group) and its control group (NEAT1+miR-NC group),and overexpressing miR-195-5p and CEBPA group (miR-195-5p+CEBPA group) and its control group (miR-195-5p+NC group). CCK-8 and EdU staining were used to detect cell proliferation ability. Transwell assay was used to detect cell migration and invasion ability. RT-qPCR was used to detect NEAT1,miR-195-5p,and CEBPA mRNA levels in cells. Western blot was used to detect CEBPA,Ki67,proliferating cell nuclear antigen (PCNA),matrix metalloproteinase (MMP)-2,MMP-9,phosphoinositide 3 kinase (PI3K),p-PI3K,protein kinase B (AKT),p-AKT,mechanistic target of rapamycin (mTOR),and p-mTOR protein levels. ③ Twenty nude mice were divided into knockdown NEAT1 expression group (sh-NEAT1 group) and its control group (sh-NC group),with ten mice in each group. Nude mice were subcutaneously injected with corresponding transfected U266 cell suspension,and the differences in various indicators of transplanted tumor were measured after 4 weeks. Results ① Compared with normal BMNC,NEAT1,CEBPA mRNA and protein levels in MM patients and MM cell lines were increased,while miR-195-5p level was decreased,and the differences were significant (t=11.697,9.272,4.352,11.639,all P<0.05). ② After overexpression of NEAT1,NEAT1,CEBPA mRNA and protein levels in cells were increased (t=12.825,5.874,13.893),while miR-195-5p level was decreased (t=4.797),the A value and EdU positive rate after 72 hours of cell culture were increased (t=9.425,5.632),the number of migration/invasion cells were increased (t=8.841,5.364),and Ki67,PCNA,MMP-2,MMP-9,p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR protein levels were increased (t=14.227,7.743,7.348,7.803,8.714,8.629,7.359),with significant differences (all P<0.05). After knockdown the expression of NEAT1,NEAT1,CEBPA mRNA and protein levels in cells were decreased (t=5.776,5.001,4.503),while miR-195-5p level was increased (t=4.456),the ability of cell proliferation,invasion and metastasis was decreased (t=6.204,8.792),with significant differences (all P<0.05). Overexpression of miR-195-5p could partially reverse the effects of overexpression of NEAT1 on the aforementioned cellular indicators,and the differences were significant (t=4.356～10.809,all P<0.05). Meanwhile,overexpression of CEBPA could partially reverse the effects of overexpression of miR-195-5p on the aforementioned cellular indicators,and the differences were significant (t=4.329～14.452,all P<0.05). ③ Knockdown NEAT1 expression could inhibit the growth of transplanted tumors in nude mice,and the differences were significant (t=5.175～18.190,all P<0.05). Conclusion LncRNA NEAT1 promotes proliferation,invasion and metastasis of MM cells by targeting miR-195-5p/CEBPA expression,which may act by activating the PI3K/AKT/mTOR pathway.

Background: Ziziphi Spinosae Semen (ZSS) contains a wide range of active components. Because existing methods cannot fully evaluate these components, a new quantitative method needs to be established for component characterization. Objective: Ziziphi Spinosae Semen has gained increasing attention in recent years, primarily as a medicinal and edible plant. The content determination of ZSS is not specified in the Chinese Pharmacopeia (2020 edition). Environmental conditions in different production areas can influence the quality of ZSS. This study aims to identify ZSS collected from various geographical origins in China. Materials and methods: High-performance liquid chromatography (HPLC) fingerprints were established using optimized HPLC-photo-diode array methods. Subsequently, similarity analysis and quantification of ZSS from different sources were conducted. Metabolites of ZSS were identified and evaluated using the UHPLC-Q Exactive HF Orbitrap MS system. Principal component analysis, hierarchical cluster analysis, and orthogonal partial least squares discriminant analysis were performed based on all peak areas. Results: In this study, the components of ZSS against insomnia were screened through network pharmacology. As revealed by the results of protein-protein interaction network analysis, Gene Ontology analysis, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, 14 core components, 10 core targets, and 25 pathways were identified. Thirty-four batches of ZSS fingerprints were established through the HPLC method, which identified 12 characteristic peaks, with 6 being qualitatively identified. An identification method for assessing differences in the chemical composition of ZSS from different origins was developed by using UHPLC-Q Exactive HF Orbitrap MS. Differential markers from various origins were screened and identified. Through multiple analyses such as principal component analysis and orthogonal partial least squares discriminant analysis, it was concluded that there were differences in ZSS metabolites from Hebei, Shandong, and Shaanxi provinces. Seventeen differential metabolites of different origins were identified. Conclusions: This study confirmed that ZSS played a synergistic role in improving insomnia through multiple components, targets, and pathways. The content of all 5 components was high, except for jujuboside B. In addition, 6 compounds in ZSS extracts from different origins differed in content, indicating that different growth environments might impact the quality of ZSS.