Objective:To discuss the changes of adenosine deaminase 2(ADA2)activity in the serum of the systemic lupus erythematosus(SLE)patients,and to clarify its clinical value in the diagnosis and disease assessment of the SLE patients.Methods:According to the inclusion and exclusion criteria,69 SLE patients(SLE group)and 69 healthy controls(control group)were enrolled as study subjects.The disease activity of SLE patients was evaluated by SLE Disease Activity Index(SLEDAI).The ADA2 activity in the serum of the subjects in both groups was detected.The patients were further divided into subgroups based on the presence or absence of the following clinical symptoms:arthritis,myositis,hematuria,proteinuria,pyuria,alopecia,new rash,mucosal ulcer,pleuritis,hypocomplementemia,elevated anti-double-stranded DNA(anti-dsDNA)antibody,thrombocytopenia,and leukopenia.The differences in serum ADA2 activity between joint symptomatic group and joint asymptomatic group were analyzed.The diagnostic efficacy of serum ADA2 activity was evaluated by receiver operating characteristic(ROC)curve analysis.The correlation between ADA2 activity and disease activity in the SLE patients was analyzed by Spearman correlation analysis.Results:Compared with control group,the ADA2 activity in the serum of the patients in SLE group was significantly increased(P<0.01).The ROC analysis results showed that when the cut-off value of ADA2 activity was set at 8.5 U·L-1,the diagnostic performance was optimal,with an area under the curve(AUC)of 0.879(95%CI:0.817-0.940),the specificity was 89.86%,and the sensitivity was 75.36%.The serum ADA2 activity was positively correlated with disease activity in the SLE patients(r=0.32,P=0.007).The subgroup analysis of clinical symptoms results showed that the serum ADA2 activity in the SLE patients with symptoms was significantly higher than that in the SLE patients without symptoms(P<0.01).No significant differences were observed in serum ADA2 activity between the SLE patients with and without myositis,hematuria,proteinuria,pyuria,alopecia,new rash,mucosal ulcer,pleuritis,hypocomplementemia,elevated anti-dsDNA antibody,thrombocytopenia,or leukopenia(P>0.05).Conclusion:The serum ADA2 activity is increased in the SLE patients and can serve as a diagnostic marker for SLE.Serum ADA2 activity is positively correlated with disease activity and is associated with arthritis in the SLE patients,suggesting its potential as an indicator for disease assessment and monitoring.

Objective To explore the potential pathogenesis of SLE and SS based on GEO database with screening differential expression genes common in systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS),analyzing their functions and identifing their expression levels. Methods The gene expression datasets of SLE and SS whole blood samples were retrieved from GEO database. Differential expression genes in peripheral blood cells of SLE and SS were screened using gene expression datasets GSE50772,GSE81622,GSE84844 and GSE48378,respectively,and the shared differential expression genes of SLE and SS were screened. Functional analysis of differentially expressed genes was performed using Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Peripheral blood from SLE and SS patients and healthy controls were collected from March 2024 to April 2024,recruited from the Second Affiliated Hospital of Air Force Medical University. Quantitative fluorescence real-time PCR (qRT-PCR) was used to identify the expression levels of 11 genes with the most significant differences in expression. Results 232 and 110 differentially expressed genes were screened for SLE and SS,respectively,among which 32 genes shared by SLE and SS were up-regulated in expression levels. Functional analysis showed that the 32 differentially expressed genes were mainly enriched in biological processes related to interferon (IFN) signaling pathways,defense response to viruses,response to viruses,negative regulation of viral genome replication,and immune response. KEGG pathway analysis showed that 32 differentialy expressed genes were associated with the process of viral infection. The clinical sample identification results showed that the expression levels of OAS3,IFI44,IFI44L and EPSTI1 were significantly elevated in PBMC of SLE and SS patients. Conclusion This study suggested that changes in biological processes related to IFN signal and viral infection response play important roles in both SLE and SS development,and may be a predisposing factor and potential biomarker for SLE and SS.

Objective:To explore the therapeutic effect of CD5L targeted therapy on a rat model of collagen-induced arthritis (CIA).Methods:The CIA rat model was established and treated with anti-CD5L antibody. The clinical arthritis score and tissue swelling degree of rats were evaluated. Twenty-four SD rats were randomly divided into the control group, the model group, the isotype control group and the CD5L antibody group. HE staining and safranin fast green staining were used to observe the synovial inflammation and cartilage erosion in the ankle joint of CIA rats. Micro-CT was used to scan the feet of CIA rats to detect bone mineral density and bone destruction. The levels of TNF-α, IL-6 and IL-8 in serum were detected by enzyme-linked immunosorbent assay (ELISA). All experimental data conforming to normal distribution were compared between groups by one-way ANOVA, and Dunnet t test was used to compare the two groups. Results:CD5L antibody improved joint swelling and deformity in CIA rats. The statistics of arthritis scores in rats showed that there was a statistically significant difference in arthritis scores between the CD5L antibody group and the isotype antibody group of rats from Day 23[Day 23 (6.6±0.5) vs. (8.2±0.7), t=-7.07, P<0.05; Day 26 (7.0±0.6) vs. (8.4±0.5), t=-7.59, P<0.05; Day 29 (7.6±0.4) vs. (9.4±0.8), t=-6.96, P<0.05; Day 32 (7.8±0.5) vs.(9.6±1.1), t=-6.50, P<0.05; Day 35 (8.2±0.7) vs. (10.4±0.7), t=-5.88, P<0.05]. The HE staining results showed that there was a statistically significant difference in the HE staining score between the CD5L antibody group and the isotype antibody group of rats [(2.5±0.6) vs. (5.0±0.8), t=-6.73, P<0.05]. The results of safranin fixation green staining showed that there was a statistically significant difference in the safranin fixation green staining score between the CD5L antibody group and the isotype antibody group of rats [(1.8±0.8) vs. (3.5±0.6), t=-5.22, P<0.05]. The Micro-CT imaging results showed that there was a statistically significant difference in bone mineral density between the CD5L antibody group and the isotype antibody group of rats [(5 618±128)g/cm 3vs. (5 202±39)g/cm 3, t=8.06, P<0.01]. The ELISA results showed that there were statistically significant differences in the contents of TNF-α, IL-6 and IL-8 in the serum of rats between the CD5L antibody group and the isotype antibody group [TNF-α: (164±22)pg/ml vs. (213±17)pg/ml, t=5.05, P<0.05; IL-6: (186±17)pg/ml vs. (230.7±25.3)pg/ml, t=4.78, P<0.05; IL-8: (384±21)pg/ml vs. (456±44)pg/ml, t=-5.21, P<0.05]. Conclusion:Targeting CD5L can effectively alleviate synovial inflammation and bone destruction in CIA rats. CD5L may be used as a potential therapeutic target for rheumatoid arthritis.

Objective To explore the potential pathogenesis of SLE and SS based on GEO database with screening differential expression genes common in systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS),analyzing their functions and identifing their expression levels. Methods The gene expression datasets of SLE and SS whole blood samples were retrieved from GEO database. Differential expression genes in peripheral blood cells of SLE and SS were screened using gene expression datasets GSE50772,GSE81622,GSE84844 and GSE48378,respectively,and the shared differential expression genes of SLE and SS were screened. Functional analysis of differentially expressed genes was performed using Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Peripheral blood from SLE and SS patients and healthy controls were collected from March 2024 to April 2024,recruited from the Second Affiliated Hospital of Air Force Medical University. Quantitative fluorescence real-time PCR (qRT-PCR) was used to identify the expression levels of 11 genes with the most significant differences in expression. Results 232 and 110 differentially expressed genes were screened for SLE and SS,respectively,among which 32 genes shared by SLE and SS were up-regulated in expression levels. Functional analysis showed that the 32 differentially expressed genes were mainly enriched in biological processes related to interferon (IFN) signaling pathways,defense response to viruses,response to viruses,negative regulation of viral genome replication,and immune response. KEGG pathway analysis showed that 32 differentialy expressed genes were associated with the process of viral infection. The clinical sample identification results showed that the expression levels of OAS3,IFI44,IFI44L and EPSTI1 were significantly elevated in PBMC of SLE and SS patients. Conclusion This study suggested that changes in biological processes related to IFN signal and viral infection response play important roles in both SLE and SS development,and may be a predisposing factor and potential biomarker for SLE and SS.

Objective:To explore the therapeutic effect of CD5L targeted therapy on a rat model of collagen-induced arthritis (CIA).Methods:The CIA rat model was established and treated with anti-CD5L antibody. The clinical arthritis score and tissue swelling degree of rats were evaluated. Twenty-four SD rats were randomly divided into the control group, the model group, the isotype control group and the CD5L antibody group. HE staining and safranin fast green staining were used to observe the synovial inflammation and cartilage erosion in the ankle joint of CIA rats. Micro-CT was used to scan the feet of CIA rats to detect bone mineral density and bone destruction. The levels of TNF-α, IL-6 and IL-8 in serum were detected by enzyme-linked immunosorbent assay (ELISA). All experimental data conforming to normal distribution were compared between groups by one-way ANOVA, and Dunnet t test was used to compare the two groups. Results:CD5L antibody improved joint swelling and deformity in CIA rats. The statistics of arthritis scores in rats showed that there was a statistically significant difference in arthritis scores between the CD5L antibody group and the isotype antibody group of rats from Day 23[Day 23 (6.6±0.5) vs. (8.2±0.7), t=-7.07, P<0.05; Day 26 (7.0±0.6) vs. (8.4±0.5), t=-7.59, P<0.05; Day 29 (7.6±0.4) vs. (9.4±0.8), t=-6.96, P<0.05; Day 32 (7.8±0.5) vs.(9.6±1.1), t=-6.50, P<0.05; Day 35 (8.2±0.7) vs. (10.4±0.7), t=-5.88, P<0.05]. The HE staining results showed that there was a statistically significant difference in the HE staining score between the CD5L antibody group and the isotype antibody group of rats [(2.5±0.6) vs. (5.0±0.8), t=-6.73, P<0.05]. The results of safranin fixation green staining showed that there was a statistically significant difference in the safranin fixation green staining score between the CD5L antibody group and the isotype antibody group of rats [(1.8±0.8) vs. (3.5±0.6), t=-5.22, P<0.05]. The Micro-CT imaging results showed that there was a statistically significant difference in bone mineral density between the CD5L antibody group and the isotype antibody group of rats [(5 618±128)g/cm 3vs. (5 202±39)g/cm 3, t=8.06, P<0.01]. The ELISA results showed that there were statistically significant differences in the contents of TNF-α, IL-6 and IL-8 in the serum of rats between the CD5L antibody group and the isotype antibody group [TNF-α: (164±22)pg/ml vs. (213±17)pg/ml, t=5.05, P<0.05; IL-6: (186±17)pg/ml vs. (230.7±25.3)pg/ml, t=4.78, P<0.05; IL-8: (384±21)pg/ml vs. (456±44)pg/ml, t=-5.21, P<0.05]. Conclusion:Targeting CD5L can effectively alleviate synovial inflammation and bone destruction in CIA rats. CD5L may be used as a potential therapeutic target for rheumatoid arthritis.

Objective To explore the regularity and potential mechanisms of medicinal and edible herbs(MEHs)in the treatment of myelosuppression through the retrieval,summary,sorting and visual analysis of relevant literature.Methods Literature about MEHs treatment for myelosuppression was reviewed in document databases,such as Web of Science,CNKI,Wanfang Data Knowledge Service Platform,China Science and Technology Journal Database,and China Biology Medicine Disc.Multivariate statistical analysis was performed using the SPSS and CiteSpace software to explore the frequency,efficacy and correlation of MEHs,as well as the potential mechanisms of MEHs in treating myelosuppression.Results A total of 123 recipes involving 170 traditional Chinese medicines(including 38 MEHs)were screened out.Five pairs of MEHs core combinations in the treatment of myelosuppression were obtained by cluster analysis.Their main functions included benefiting qi and nourishing blood,invigo-rating spleen and dispelling dampness,replenishing qi and solidifying kidney.The potential mechanisms were associated with many related signal pathways,such as Janus kinase 2-signal transducer and activator of transcription 5 andβ-catenini.Conclusion MEHs such as radix astragali combined with angelica sinensis,poria cocos and codonopsis pilosula are mainly used clinically to treat myelosuppression induced by chemotherapy.They play their therapeutic effects by promoting proliferation and delaying senescence of hematopoietic stem cells.

Background::CD5L (CD5 molecular-like) plays an important role in lipid metabolism and immune regulation. This study aimed to investigate the roles of CD5L on liver hepatocellular carcinoma (LIHC).Methods::We analyzed the CD5L mRNA expression and its potential prognostic value based on The Cancer Genome Atlas and Gene Expression Omnibus databases. Immunohistochemical analysis was used to investigate the CD5L levels in LIHC tissues. Serum CD5L levels in LIHC were detected by enzyme-linked immunosorbent assay. Cell Counting Kit-8 (CCK-8) assay was used to investigate the effect of CD5L treatment on HepG2 and QSG-7701 cell proliferation. CD5L expression correlated genes were exhumed based on the LinkedOmics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for CD5L associated genes were performed. The correlation between CD5L and tumor immune infiltration was analyzed by using Tumor Immune Estimation Resource (TIMER) 2.0.Results::CD5L mRNA and protein levels were significantly decreased in LIHC tumor tissue compared with non-tumor control tissues. Moreover, serum CD5L levels were significantly lower in LIHC patients than that in healthy subjects. Gene Expression Profiling Interactive Analysis 2 and Kaplan-Meier plotter analysis showed that a high-CD5L expression was correlated with favorable overall survival in LIHC patients, except the LIHC patients with hepatitis virus. CCK-8 results showed that CD5L treatment significantly decreased HepG2 cell proliferation in a concentration-dependent manner, and CD5L treatment had no effect on the proliferation of non-tumor hepatocyte line QSG-7701. CD5L associated genes were enriched in the immune response biological process, and CD5L expression levels were positively correlated with the immune infiltrates of CD8 + T cell and M1 macrophage cells but negatively correlated with CD4 + T cells and M0 macrophage cell infiltration. Conclusions::Exogenous CD5L inhibits cell proliferation of hepatocellular carcinoma. CD5L may act as a role of prognostic marker.

[摘 要] 目的：探讨干扰B7-H4表达对乳腺癌细胞增殖、凋亡、周期以及相关下游分子表达的影响。方法：利用脂质体转染技术分别将特异性靶向B7-H4的siRNA（siB7-H4）及其阴性对照（siNC）转染至对数生长期的乳腺癌T47D和MCF-7细胞，分别命名为T47D-siB7-H4、T47D-siNC、MCF-7-siB7-H4和MCF-7-siNC组。用qPCR法和WB法验证siRNA干扰效果及其对细胞周期分子cyclin D1表达的影响，CCK-8法和FCM分别检测干扰B7-H4表达对T47D和MCF-7细胞增殖、周期和凋亡的影响，qPCR法检测B7-H4干扰对E2F家族相关转录因子表达的影响。结果：成功构建干扰B7-H4表达的乳腺癌T47D和MCF-7细胞。与T47D-siNC和MCF-7-siNC组相比，T47D-siB7-H4和MCF-7-siB7-H4组细胞中B7-H4 mRNA和蛋白表达水平均显著降低、细胞增殖能力显著降低（均P<0.01），并伴有G1/S期细胞周期阻滞以及cyclin D1表达下调（均P<0.01），但细胞凋亡率差异无统计学意义（均P>0.05）。与T47D-siNC相比，干扰B7-H4后T47D细胞中E2F1、E2F2、E2F7和E2F8 mRNA水平有不同程度的降低（均P<0.01）；与MCF-7-siNC相比，干扰B7-H4后MCF-7细胞中E2F1、E2F2、E2F3、E2F7和E2F8 mRNA水平均有不同程度的降低（P<0.05或P<0.01）。结论：干扰乳腺癌细胞B7-H4表达可下调cyclin D1和E2F家族相关转录因子的表达，导致细胞周期阻滞并抑制细胞增殖。

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.