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

Objective:To analyze the awareness of HCV infection status and willingness for HCV-RNA testing among hepatitis C cases in four provinces in China and to provide a reference for adjusting HCV prevention and control strategies.Methods:From September 2021 to September 2022, a cross-sectional survey was conducted using stratified random cluster sampling in four provinces (Jiangsu, Henan, Hubei, and Yunnan) in China, with an estimated sample size of 6 468 participants. The questionnaire included sociodemographic information, HCV infection awareness, willingness for HCV-RNA testing, and history of high-risk behaviors from the survey participants. Logistic regression models were used to analyze the factors associated with HCV infection awareness and willingness for HCV-RNA testing among hepatitis C cases. Statistical analysis was performed using R 4.1.3 software.Results:A total of 10 563 hepatitis C cases were surveyed. The awareness rate of HCV infection was 86.74% (9 162/10 563), and the willingness rate for HCV-RNA testing was 85.21% (9 001/10 563). Multivariate logistic regression models analysis showed that the awareness rate of HCV infection was lower among individuals aged ≥60 years, urban residents (with New Rural Cooperative Medical Insurance ), those without a history of blood transfusion, those without a history of paid blood donation, those without a history of injection drug use, and those without a family member with hepatitis C case.The awareness rate was higher among individuals with high or technical secondary school education, college education or above, and those married with a spouse (all P<0.05). In terms of willingness for HCV-RNA testing, it was lower among females, individuals aged ≥60 years, and those without a history of blood transfusion, paid blood donation, or injection drug use. The willingness was higher among farmers or migrant workers, employees of enterprises or institutions, and those in other occupations (all P<0.05). Conclusions:There was room for improvement in the awareness proportion of HCV infection and willingness for HCV-RNA testing among hepatitis C cases in the four provinces of China. More convenient policies and measures should be provided to increase the awareness rate of HCV infection and the willingness to undergo HCV-RNA testing in this population.

Objective 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.Conclusion QJZ inhibits B cell differentiation and alleviates renal damage in systemic lupus erythematosus possibly by suppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.

Objective 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.Conclusion QJZ can improve renal damage in MRL/lpr mice possibly by inhibiting overactivation of the MyD88/NF-κB pathway.

Objective To observe the value of quantitative parameters of synthetic MRI(syMRI)and multiplexed sensitivity encoding diffusion weighted imaging(MUSE-DWI)for predicting pathological characteristics of endometrial cancer(EC).Methods Totally 125 patients with single EC were retrospectively collected.Quantitative parameters of EC,including T1,T2,proton density(PD)and apparent diffusion coefficient(ADC)values were measured based on preoperative syMRI and MUSE-DWI.Univariate analysis and multivariate logistic regression were performed to explore quantitative parameters of EC in order to screen independent predictors of EC with different pathologic characteristics for establishing combined models.Receiver operating characteristic curves were drawn,the area under the curves(AUC)were calculated to evaluate the predictive efficacy of models.Results Among 125 cases,type Ⅰ(estrogen-dependent type)and type Ⅱ(non-estrogen-dependent type)EC were found in 109 and 16 cases,respectively,including 94 cases of medium-low grade(31 of grade G1+63 of grade G2)and 31 cases of high grade(grade G3)EC,93 low-risk type(grade G1-2 type Ⅰ EC)and 32 high-risk type(grade G3 type Ⅰ EC+type Ⅱ EC),with muscular invasion＜1/2 in 84 cases and≥1/2 in 41 cases.Meanwhile,vascular infiltration was found in 41 cases.Lymph node invasion was detected in 18 cases but not in 105 cases,which remained unclear in 2 cases.T2 value of type Ⅰ EC was higher than that of type Ⅱ EC(P＜0.05).T2 and ADC values of high grade or high-risk type EC were lower than those of medium-low grade or low-risk type EC(all P＜0.05).T1,PD and ADC values of EC with muscular invasion≥1/2 were all lower than of those with muscular invasion＜1/2(all P＜0.05).No significant difference of other quantitative MRI parameters was observed among EC with different pathological features(all P＞0.05).ADC value was independent predictor of EC grade and risk type,PD and ADC values were both independent predictors of EC muscular invasion(all P＜0.05).The AUC of PD+ADC model for predicting muscular invasion depth of EC was 0.739,which was not significantly different with that of single PD and ADC models(0.692 and 0.707)(both P＞0.05).Conclusion Quantitative parameters of syMRI and MUSE-DWI could be used in clinical prediction of pathological characteristics of EC.

Objective:To analyze the awareness of HCV infection status and willingness for HCV-RNA testing among hepatitis C cases in four provinces in China and to provide a reference for adjusting HCV prevention and control strategies.Methods:From September 2021 to September 2022, a cross-sectional survey was conducted using stratified random cluster sampling in four provinces (Jiangsu, Henan, Hubei, and Yunnan) in China, with an estimated sample size of 6 468 participants. The questionnaire included sociodemographic information, HCV infection awareness, willingness for HCV-RNA testing, and history of high-risk behaviors from the survey participants. Logistic regression models were used to analyze the factors associated with HCV infection awareness and willingness for HCV-RNA testing among hepatitis C cases. Statistical analysis was performed using R 4.1.3 software.Results:A total of 10 563 hepatitis C cases were surveyed. The awareness rate of HCV infection was 86.74% (9 162/10 563), and the willingness rate for HCV-RNA testing was 85.21% (9 001/10 563). Multivariate logistic regression models analysis showed that the awareness rate of HCV infection was lower among individuals aged ≥60 years, urban residents (with New Rural Cooperative Medical Insurance ), those without a history of blood transfusion, those without a history of paid blood donation, those without a history of injection drug use, and those without a family member with hepatitis C case.The awareness rate was higher among individuals with high or technical secondary school education, college education or above, and those married with a spouse (all P<0.05). In terms of willingness for HCV-RNA testing, it was lower among females, individuals aged ≥60 years, and those without a history of blood transfusion, paid blood donation, or injection drug use. The willingness was higher among farmers or migrant workers, employees of enterprises or institutions, and those in other occupations (all P<0.05). Conclusions:There was room for improvement in the awareness proportion of HCV infection and willingness for HCV-RNA testing among hepatitis C cases in the four provinces of China. More convenient policies and measures should be provided to increase the awareness rate of HCV infection and the willingness to undergo HCV-RNA testing in this population.

Objective To observe the value of quantitative parameters of synthetic MRI(syMRI)and multiplexed sensitivity encoding diffusion weighted imaging(MUSE-DWI)for predicting pathological characteristics of endometrial cancer(EC).Methods Totally 125 patients with single EC were retrospectively collected.Quantitative parameters of EC,including T1,T2,proton density(PD)and apparent diffusion coefficient(ADC)values were measured based on preoperative syMRI and MUSE-DWI.Univariate analysis and multivariate logistic regression were performed to explore quantitative parameters of EC in order to screen independent predictors of EC with different pathologic characteristics for establishing combined models.Receiver operating characteristic curves were drawn,the area under the curves(AUC)were calculated to evaluate the predictive efficacy of models.Results Among 125 cases,type Ⅰ(estrogen-dependent type)and type Ⅱ(non-estrogen-dependent type)EC were found in 109 and 16 cases,respectively,including 94 cases of medium-low grade(31 of grade G1+63 of grade G2)and 31 cases of high grade(grade G3)EC,93 low-risk type(grade G1-2 type Ⅰ EC)and 32 high-risk type(grade G3 type Ⅰ EC+type Ⅱ EC),with muscular invasion＜1/2 in 84 cases and≥1/2 in 41 cases.Meanwhile,vascular infiltration was found in 41 cases.Lymph node invasion was detected in 18 cases but not in 105 cases,which remained unclear in 2 cases.T2 value of type Ⅰ EC was higher than that of type Ⅱ EC(P＜0.05).T2 and ADC values of high grade or high-risk type EC were lower than those of medium-low grade or low-risk type EC(all P＜0.05).T1,PD and ADC values of EC with muscular invasion≥1/2 were all lower than of those with muscular invasion＜1/2(all P＜0.05).No significant difference of other quantitative MRI parameters was observed among EC with different pathological features(all P＞0.05).ADC value was independent predictor of EC grade and risk type,PD and ADC values were both independent predictors of EC muscular invasion(all P＜0.05).The AUC of PD+ADC model for predicting muscular invasion depth of EC was 0.739,which was not significantly different with that of single PD and ADC models(0.692 and 0.707)(both P＞0.05).Conclusion Quantitative parameters of syMRI and MUSE-DWI could be used in clinical prediction of pathological characteristics of EC.

Objective To observe the value of MRI for differential diagnosis of ovarian granulosa cell tumor(OGCT)and ovarian thecoma-fibroma(OTF).Methods Data of 37 females with OGCT(OGCT group)and 74 with OTF(OTF group)were retrospectively analyzed.MRI parameters were compared between groups.Multiple logistic regression analysis was performed,and the efficacy of each parameter alone and their combination for distinguishing OGCT and OTF were observed.Results Significant differences of cystic-solid classification,degree of cystic changes,the maximum diameter of cyst area of lesions,T2WI signal,enhancement degree and apparent diffusion coefficient(ADC)of the solid part of lesions,presence of honeycomb sign/cheese sign,presence of tumor blood vessels and bleeding were found between groups(all P＜0.05).Degree of cystic changes,ADC and presence of honeycomb sign/cheese sign were impact factors of MRI for distinguishing OGCT and OTF.The area under the curve(AUC)of the above three for distinguishing OGCT and OTF was 0.834,0.868 and 0.744,respectively,and of the combination was 0.934,greater than any alone(all P＜0.05).Conclusion MRI features such as degree of cystic changes,ADC and presence of honeycomb sign/cheese sign were helpful for distinguishing OGCT and OTF.

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.