OBJECTIVES: To investigate the mechanism of Qihuang Jianpi Zishen Granules (QJZ) for ameliorating renal damage in MRL/lpr mice. METHODS: With 6 female C57BL/6 mice as the normal control group, 30 female MRL/lpr mice were randomized into model group, QJZ treatment groups at low, moderate and high doses, and prednisone treatment group (n=6). After 8 weeks of treatment, the mice were examined for 24-h urine protein, creatinine and albumin levels, serum levels of IgG, complement 3 (C3), C4, anti-dsDNA, interferon γ (IFN‑γ) and interleukin 17 (IL-17). Kidney tissues were sampled for histopathological examination with HE staining and observation of glomerular ultrastructure changes using transmission electron microscopy (TEM). The expressions of MyD88/NF-κB pathway-related molecules in the kidney tissue were detected using RT-qPCR, Western blotting and immunohistochemistry. RESULTS: Compared with those in the model group, the mice treated with QJZ at the 3 doses and prednisone showed significant reductions in the renal injury biomarkers and serum IgG, anti-dsDNA, IFN‑γ and IL-17 levels and elevation of serum C3 and C4 levels. HE staining revealed lessened glomerular endothelial cell proliferation and mesangial thickening in all the treatment groups. TEM observation further demonstrated reduced electron-dense deposits and diminished inflammatory cell infiltration in the glomeruli in the intervention groups. QJZ at the 3 doses and prednisone treatment all significantly lowered renal expression levels of MyD88, NF-κB, p65 and p52 in the mouse models. CONCLUSIONS QJZ can improve renal damage in MRL/lpr mice possibly by inhibiting overactivation of the MyD88/NF-κB pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Myeloid Differentiation Factor 88/metabolism* ; Mice ; NF-kappa B/metabolism* ; Signal Transduction/drug effects* ; Kidney/metabolism* ; Interleukin-17

OBJECTIVES: To investigate the efficacy of Qihuang Jianpi Zishen Granules (QJZ) for inhibiting renal B cell differentiation in MRL/lpr mice and explore its underlying mechanism. METHODS: Thirty 8-week-old female MRL/lpr mice were randomly divided into model group, QJZ group, prednisone (Pred) group, QJZ+Pred group, and AIM2 inhibitor group (n=6), with 6 8-week-old female C57BL/6 mice as the normal control group. After treatments with normal saline, QJZ, Pred, or AIM2 inhibitor for 8 weeks, the mice were examined for urinary total protein-to-creatinine ratio (TPCR) and albumin-to-creatinine ratio (ACR), serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal histopathology (with HE, Masson, and PAS staining) and ultrastructural changes (with electron microscopy). ELISA, immunohistochemistry, immunofluorescence staining and flow cytometry were used to detect blood levels of anti-dsDNA antibodies, cytokines and chemokines, renal deposition of complement components C3 and C4, renal expressions of AIM2, CD19, CD27 and CD138, and changes in splenic B lymphocyte subsets. The effect of QJZ on the AIM2/Blimp-1/Bcl-6 signaling axis was examined using Western blotting. RESULTS: QJZ treatment significantly improved Cr, BUN, TPCR and ACR in MRL/lpr mice, ameliorated renal pathologies, reduced the expressions of ds-DNA, BAFF, IL-21, CXCL12, CXCL13, C3 and C4, and increased IL-10 levels. QJZ significantly downregulated renal expressions of the key B-cell transcription factors Blimp-1 and XBP-1, upregulated Bcl-6 and PAX5 expressions, inhibited B-cell differentiation, and lowered the expressions of AIM2, CD27, CD138 and CD69. Inhibition of AIM2 similarly reduced renal Blimp-1 and XBP-1 expressions, increased Bcl-6 and PAX5 levels, suppressed B-cell differentiation, decreased IgG production, reduced C3 and C4 deposition, and alleviated renal pathology in MRL/lpr mice. CONCLUSIONS QJZ inhibits B cell differentiation and alleviates renal damage in systemic lupus erythematosus possibly by suppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred MRL lpr ; Female ; Mice ; Mice, Inbred C57BL ; Cell Differentiation/drug effects* ; B-Lymphocytes/drug effects* ; Proto-Oncogene Proteins c-bcl-6/metabolism* ; Kidney/drug effects* ; DNA-Binding Proteins/metabolism* ; Signal Transduction ; Lupus Nephritis

ObjectiveTo investigate the clinical efficacy of Qihuang Jianpi Zishen Granules in the treatment of systemic lupus erythematosus （SLE） and its effect on the signal transducer and activator of tranSCription 3/mammalian target of rapamycin （STAT3/mTOR） signaling pathway， and to decipher the possible mechanism. MethodSixty female SLE patients who met the criteria in the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2022 to May 2023 were selected and randomized into a control group and an observation group （30 cases in each group）. The control group was treated with prednisone acetate + hydroxychloroquine sulfate orally， and the observation group was additionally treated with Qihuang Jianpi Zishen granules. The treatment lasted for 8 weeks. The SLE disease activity （SLEDAI）， TCM syndrome score， erythrocyte sedimentation rate （ESR）， hypersensitive C-reactive protein （hs-CRP）， immune indexes ［immunoglobulin G （IgG）， C3， C4， CD4⁺， and CD8⁺］， interleukin （IL）-17， IL-23， interferon （IFN）-γ， 24 h urinary protein （24 h PRO）， serum creatinine （SCr）， and expression of proteins ［STAT3， phosphorylated （p）-STAT3， mTOR protein and STAT3，mTOR mRNA］ in the STAT3/mTOR signaling pathway were determined before and after treatment. In addition， the adverse reactions were recorded. ResultAfter 8 weeks of treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （70.00%， 21/30） in the control group （χ²=4.007， P<0.05）. After treatment， both groups showed declined SLEDAI， TCM syndrome score， ESR， hs-CRP， IgG， CD8⁺， IL-17， IL-23， IFN-γ， 24 h PRO， SCr， and expression of proteins in the STAT3/mTOR pathway （P<0.01） and elevated levels of C3， C4， and CD4⁺ （P<0.01）. Moreover， the observation group had lower SLEDAI， TCM syndrome score， ESR， hs-CRP， IgG， CD8⁺， IL-17， IL-23， IFN-γ， 24 h PRO， SCr， and expression of proteins in the STAT3/mTOR pathway （P<0.05， P<0.01） and higher levels of C3， C4， and CD4⁺ （P<0.05， P<0.01） than the control group after treatment. Neither group showed serious adverse reactions during the treatment period. ConclusionQihuang Jianpi Zishen Granules can ameliorate the inflammatory response， reduce the disease activity， and mitigate the kidney injury in SLE by inhibiting the STAT3/mTOR signaling pathway to regulate the immune function.

Objective:To explore the expression of homologous recombination repair (HRR) deficiency related genes in endometrial cancer and their relationship with clinical pathological features and immune infiltration.Methods:A total of 53 patients with endometrial cancer (endometrial cancer group) who underwent surgical treatment at the Affiliated People′s Hospital of Shandong First Medical University from June 2018 to June 2020 were selected as the study subjects. Clinical data of the patients were retrospectively analyzed, and 50 healthy women who underwent physical examinations were selected as the control group. Clinical and pathological characteristics of 53 patients with endometrial cancer were collected, and real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was performed Methods The mRNA expressions of human breast cancer susceptibility gene 1 (BRCA1), tumor suppressor gene homologous loss phosphatase tensin gene (PTEN) on chromosome 10 in the peripheral blood of the subjects were detected, and the proportions of CD 4+ T cell subsets in peripheral blood monocytes were detected by flow cytometry; Pearson analysis of the correlation between peripheral blood BRCA1, PTEN mRNA expression and various subsets of CD 4+ T cell; Analysis of prognostic factors for endometrial cancer using COX risk regression model. Results:The peripheral blood BRCA1 and PTEN mRNA expression levels in patients with endometrial cancer were higher than those in the healthy control group: 2.87 ± 0.65 vs. 1.02 ± 0.13, 3.25 ± 0.74 vs. 1.01 ± 0.20, and the differences were statistically significant ( P<0.01). The proportion of peripheral blood helper T cell-2 (Th2), helper T cell-17 (Th17), regulatory T cell (Treg) and helper T cell-22 (Th22) in patients with endometrial cancer was significantly higher than that in the healthy control group: (10.72 ± 1.33)% vs. (5.43 ± 0.80)%, (9.78 ± 0.80)% vs. (3.31 ± 0.62)%, (10.81 ± 1.29)% vs. (5.74 ± 0.69)%, (6.09 ± 0.70)% vs. (3.09 ± 0.73)%, and the proportion of helper T cell-1 (Th1) was significantly lower than that in the healthy control group: (5.54 ± 0.90)% vs. (13.07 ± 2.55)%, the difference was statistically significant ( P<0.01). The peripheral blood BRCA1 and PTEN mRNA expression levels were significantly higher in patients with muscle infiltration depth ≥1/2, histological grade G 2 to G 3, lymph node metastasis, and International Federation of Obstetrics and Gynecology (FIGO) stage Ⅲ to Ⅳ than in patients with muscle infiltration depth<1/2, histological grade G 1, no lymph node metastasis, and FIGO stage Ⅰ to Ⅱ, with statistical significance ( P<0.01 or<0.05). Peripheral blood BRCA1 and PTEN mRNA were significantly positively correlated with Th2, Th17, Treg and Th22 ratios ( P<0.01), and negatively correlated with Th1 ratios ( P<0.01). COX risk regression analysis showed that histological grading, FIGO staging, depth of muscle infiltration, peripheral blood BRCA1 and PTEN mRNA expression with lymph node metastasis were all independent prognostic factors for endometrial cancer ( P<0.01 or<0.05). Conclusions:HRR deficiency related genes BRCA1 and PTEN mRNA exhibit high levels in patients with endometrial cancer, and are closely related to muscle infiltration depth, histological grading, lymph node metastasis, and FIGO staging. They can also affect the immune microenvironment of endometrial cancer patients, thereby affecting disease progression and prognosis.

Rheumatoid arthritis(RA)is a common chronic autoimmune disease with synovitis as its pathological basis and erosive arthritis as its main symptom.Pathogenesis of RA is complex,combination of genetic factors,environmental factors,immune cells,cytokines and autoantibodies causes joint injury,bone destruction and multi-system disease of RA.However,the above mecha-nisms can not fully explain the poor prognosis,high disability rate and poor clinical treatment effect of RA.Therefore,exploring new pathogenesis and therapeutic targets of RA is the focus of RA research.In recent years,with the deepening of RA research,it has been found that there is a new form of cell death in pathological process of RA,namely ferroptosis.Ferroptosis is a type of cell death caused by inhibition of glutathione peroxidase activity and accumulation of lipid reactive oxygen species.Previous studies have con-firmed the close correlation between RA and ferroptosis,this paper mainly explores ferroptosis-related signal pathways that affect the change and development of RA disease from the perspective of regulating the main signal pathways of ferroptosis,so as to find new therapeutic targets for RA and new therapeutic ideas for research.

ObjectiveTo investigate the clinical efficacy and safety of Qihuang Jianpi Zishen granules in the treatment of cardiac involvement in systemic lupus erythematosus （SLE）. MethodA total of 62 SLE patients with cardiac involvement treated in the Department of Rheumatology and Immunology， the First Affiliated Hospital of Anhui University of Chinese Medicine from June 2021 to December 2022 were randomized into control and observation groups （n=31）. The control group was treated with methylprednisolone tablets and hydroxychloroquine sulfate tablets， and the observation group with Qihuang Jianpi Zishen granules on the basis of the therapy in the control group. After 12 weeks of treatment， the two groups were compared in terms of the therapeutic effect， cardiac function indicators ［left atrial end-diastolic diameter （LADd）， left ventricular end-diastolic diameter （LVDd）， left ventricular posterior wall thickness （LVPWTd）， peak blood flow velocity in early diastolic period （peak E）， peak blood flow velocity in late diastolic period （peak A）， E/A ratio， stroke volume （SV）， left ventricular ejection fraction （LVEF）， left ventricular short axis shortening rate （LVFS）， and B-type natriuretic peptide （BNP）］， vascular damage indicators ［nitric oxide （NO）， endothelin-1 （ET-1）， vascular endothelial growth factor （VEGF）， and homocysteine （Hcy）］， inflammation indicators ［erythrocyte sedimentation rate （ESR） and hypersensitive C-reactive protein （Hs-CRP）］， anti-double-stranded DNA （dsDNA） antibodies， disease activity index （SLEDAI） score， mitigation of symptoms and signs， and occurrence of adverse reactions. ResultThe total response rate in the observation group was 87.09%， which was higher than that （67.74%） in the control group （P<0.01）， and the incidence of adverse reactions had no significant difference between the two groups. After treatment， the control group showed lowered LVDd， LVPWTd， BNP， ET-1， VEGF， and Hcy （P<0.05） and increased E peak， E/A ratio， SV， LVEF， and LVFS （P<0.05）. In the observation group， LADd， LVDd， LVPWTd， peak A， BNP， NO， ET-1， VEGF， and Hcy decreased （P<0.05）， while peak E， E/A ratio， SV， LVEF and LVFS increased （P<0.05） after treatment. The treatment in both groups decreased the scores of palpitation， chest tightness， dyspnea， and edema （P<0.05）， reduced ESR， Hs-CRP， ds-DNA， and SLEDAI （P<0.05）. After treatment， the observation group had lower LADd， LVDd， LVPWTd， peak A， BNP， and scores of palpation， chest tightness， dyspnea， and edema （P<0.05） and higher peak E， E/A ratio， SV， LVEF， and LVFS （P<0.05） than the control group. In addition， the observation group had lower NO， ET-1， VEGF， Hcy， ESR， Hs-CRP， ds-DNA， and SLEDAI than the control group （P<0.05）. ConclusionQihuang Jianpi Zishen granules combined with hydroxychloroquine sulfate and methylprednisolone can improve multiple indicators and mitigate the symptoms and signs of SLE patients with cardiac involvement， demonstrating a clinical application value.

Long non-coding RNAs(lncRNAs)can be involved in regulating gene expression through multiple interactions with DNA,RNA or proteins.Studies have shown that lncRNAs not only regulate innate immune response,but also regulate immune cell development and adaptive immunity.According to recent reports,a number of lncRNAs play a role in the pathogenesis of immune-mediated inflammatory diseases,including systemic lupus erythematosus(SLE),and may become a diagnostic marker and prognostic reference for diseases.This paper summarizes the research progress of lncRNAs in SLE,with the hope of providing more new ideas and methods for the study of SLE.