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 analyze the prevalence of latent tuberculosis infection(LTBI)among relevant healthcare workers(HCWs)in designated tuberculosis medical institutions(MIs)in Yantai City,and explore its influencing factors.Methods The cluster random sampling method was adopted to select two county-and district-level desig-nated tuberculosis MIs.All HCWs underwent questionnaire survey and creation tuberculin skin test(C-TST)at the same time,and the influencing factors for LTBI were analyzed.Results A total of 215 HCWs from designated tu-berculosis MIs were included for analysis,37 were diagnosed with LTBI,with an infection rate of 17.21％(95％CI:12.42％-22.93％).Multivariate logistic regression analysis showed that clinicians(OR=3.19,95％CI:1.05-9.69),laboratory technician(OR=5.90,95％CI:1.21-28.77),working years≥10 years(OR=3.31,95％CI:1.39-7.90),and tuberculosis history of family members(OR=6.49,95％CI:1.01-41.46)were independent risk factors for LTBI.Conclusion The infection risk of clinicians and laboratory technicians who directly contact with tuberculosis patients or Mycobacterium tuberculosis is higher than that of other HCWs,and is related to the length of working years.It is suggested that healthcare-associated infection control measures should be streng-thened,and tuberculosis active screening should be carried out regularly for HCWs in key departments.

Objective To analyze the prevalence of latent tuberculosis infection(LTBI)among relevant healthcare workers(HCWs)in designated tuberculosis medical institutions(MIs)in Yantai City,and explore its influencing factors.Methods The cluster random sampling method was adopted to select two county-and district-level desig-nated tuberculosis MIs.All HCWs underwent questionnaire survey and creation tuberculin skin test(C-TST)at the same time,and the influencing factors for LTBI were analyzed.Results A total of 215 HCWs from designated tu-berculosis MIs were included for analysis,37 were diagnosed with LTBI,with an infection rate of 17.21％(95％CI:12.42％-22.93％).Multivariate logistic regression analysis showed that clinicians(OR=3.19,95％CI:1.05-9.69),laboratory technician(OR=5.90,95％CI:1.21-28.77),working years≥10 years(OR=3.31,95％CI:1.39-7.90),and tuberculosis history of family members(OR=6.49,95％CI:1.01-41.46)were independent risk factors for LTBI.Conclusion The infection risk of clinicians and laboratory technicians who directly contact with tuberculosis patients or Mycobacterium tuberculosis is higher than that of other HCWs,and is related to the length of working years.It is suggested that healthcare-associated infection control measures should be streng-thened,and tuberculosis active screening should be carried out regularly for HCWs in key departments.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective To investigate the predictive value of pan-immune-inflammation value(PIV),blood urea nitrogen to albumin ratio(BAR),collateral circulation and National Institutes of Health stroke scale(NIHSS)score for disease progression and short-term prognosis in patients with acute perforating artery cerebral infarction(APACI).Methods Patients with APACI admitted to the Neurology Department of Anhui NO.2 Provincial People's Hospital from January 2019 to October 2024 were retrospectively enrolled in this study.General and clinical data,including age,gender,previous history(hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,drinking history,NIHSS scores at admission were collected.Fasting venous blood samples were collected from the patients within 24 h after admission to detect levels of neutrophils,lymphocytes,monocytes,platelets,blood urea nitrogen,and serum albumin.PIV(PIV=neutrophils × platelets × monocytes/lymphocytes)and BAR were calculated.The location of lesions and Fazekas classification of white matter lesions were evaluated using head MRI and MR angiography at admission.Collateral circulation status was assessed based on CT angiography upon admission.Disease progression was defined through comparing the NIHSS score at 72-hour after admission to the score at admission(an increase of 2 or more points in NIHSS score indicating disease progression).The patients were divided into a progression group and a non-progression group based on the increase in NIHSS score,as aforementioned.Patients follow-up was conducted through phone call or outpatient visits at 90 d after discharge.The modified Rankin scale(mRS)was used to evaluate the prognosis,with a mRS score of 0-2 indicates good prognosis,and a 3-6 indicates poor prognosis.Factors with statistically significant differences in univariate analysis were included in a multivariate Logistic regression analysis to explore the influencing factors of disease progression and poor prognosis in patients with APACI.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each indicator for disease progression and poor prognosis in patients with APACI.Results A total of 165 patients with APACI were enrolled in this study,including 121 males and 44 females,aged 27-86 years,with an average of(61±11)years.Among all patients enrolled,56 patients were included in the progression group and 109 patients in the non-progression group,124 patients showed good prognosis and 41 patients had poor prognosis.No statistically significant differences were found in age,gender,smoking history,drinking history,hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and Fazekas classification of white matter lesions between the progression group and the non-progression group(all P＞0.05).While the NIHSS score at admission,proportion of poor collateral circulation,PIV and BAR in the progression group were significantly higher than those in the non-progression group(all P＜0.05).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.177,95％CI 1.001-1.384,P=0.049),poor collateral circulation(OR,3.107,95％CI 1.216-7.939,P=0.018),high PIV(OR,1.006,95％CI 1.003-1.009,P=0.001),and high BAR(OR,1.610 × 109,95％CI 5.769 × 104-4.494 × 1013,P＜0.01)were independent risk factors of disease progression in patients with APACI.ROC curve analysis results showed that the area under the curve(AUC)of combination of PIV,BAR,collateral circulation and NIHSS score at admission for predicting disease progression in patients with APACI was 0.914(95％ CI0.861-0.952,P＜0.01),which was greater than that of each indicator(all P＜0.05).No statistically significant differences were found in smoking,drinking,hypertension,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and BAR between the poor prognosis and the good prognosis group(all P＞0.05).Compared with the good prognosis group,the poor prognosis group had significantly older age and higher proportion of patients with diabetes,NIHSS score at admission,proportion of patients with poor collateral circulation,and PIV(all P＜0.05).Moreover,the proportion of men in the poor prognosis group was lower than that in the good prognosis group(P=0.039).There was a statistically significant difference between the good prognosis group and the poor prognosis group in the Fazekas classification of white matter lesions(P＜0.01).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.345,95％CI 1.081-1.674,P=0.008),poor collateral circulation(OR,3.903,95％CI 1.061-14.355,P=0.040),and high PIV(OR,1.011,95％CI 1.005-1.017,P＜0.01)were independent risk factors of poor prognosis in patients with APACI.The AUC for predicting poor prognosis in patients with APACI through combining PIV,collateral circulation and NIHSS score at admission was 0.911(95％CI 0.857-0.950,P＜0.01),which is greater than using poor collateral circulation or NIHSS score at admission alone(both P＜0.05).However,there was no statistically significant difference in AUC between the PIV,collateral circulation and NIHSS score combined predictive model and the PIV(alone)predictive model(P＞0.05).Conclusions High PIV,high BAR,poor collateral circulation,and high NIHSS score at admission were independent risk factors of disease progression in patients with APACI.Combination of these four indices demonstrates relatively high predictive value for disease progression.In addition,high PIV,poor collateral circulation,and high NIHSS score at admission are independent risk factors of poor prognosis in patients with APACI.Joint detection of the three indices may assist in short-term prognosis evaluation of patients with APACI.

Objective:To observe and assess the clinical value of electrophysiology of ocular surface in the diagnosis and treatment of blepharospasm in Meige syndrome (MS).Methods:A single-center, cross-sectional study. A total of 413 patients diagnosed with MS and undergoing surgical treatment at the Henan Provincial Meige Syndrome Diagnosis and Treatment Center of the Henan Provincial Third People′s Hospital from May 2022 to December 2023 were included as the MS group. A total of 110 age- and gender-matched spouses of patients and community volunteers were selected as the control group. The bioelectricity detection program of the electrooculogram was used; the frequency bandwidth was set at 0.3 to 300.0 Hz. Surface electrodes were employed to record the surface electrophysiological manifestations of the corrugator supercilii muscle and the lower orbicularis oculi muscle, as well as the conditions and temporal characteristics of spasm waves. Based on the amplitude and waveform of the electrophysiology of ocular surface signals, it can be classified into 0-4 grades. The blepharospasm was divided into conditionally induced type, spastic type, reverse spastic type, and oro-ocular elicited type. All patients were treated with neural circuit occlusion, and the postoperative follow-up time was 4.1 (0.5-19.0) months. The distribution of different grades of electrophysiology of ocular surface in the MS and control group at baseline were observed, as well as within the MS group at the last follow-up visit. Additionally, the blepharospasm grades in the MS group were also assessed. The comparison of the distribution of the number of eyes with different grades of electrophysiology of ocular surface between groups was conducted using the Mann-Whitney U test. Results:At baseline, in the MS group, the number of cases with corrugator supercilii muscle amplitudes and morphologies graded from 0 to 4 were as follows: 15 (3.60%, 15/413) for grade 0, 95 (23.00%, 95/413) for grade 1, 142 (34.38%, 142/413) for grade 2, 127 (30.75%, 127/413) for grade 3, and 34 (8.24%, 34/413) for grade 4. In the control group, the corresponding numbers of individuals were 82 (74.54%, 82/110) for grade 0, 24 (21.82%, 24/110) for grade 1, 4 (3.64%, 4/110) for grade 2, 0 (0.00%, 0/110) for grade 3, and 0 (0.00%, 0/110) for grade 4. For the orbicularis oculi muscle, there were 35 cases (8.47%) in grade 0, 124 cases (30.03%) in grade 1, 150 cases (36.32%) in grade 2, 90 cases (21.79%) in grade 3, and 14 cases (3.39%) in grade 4 in the MS group. In the control group, there were 86 cases (78.18%) in grade 0, 24 cases (21.82%) in grade 1, and 0 cases in grades 2, 3, and 4. There were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between the MS and control group ( Z=-14.51, -13.86; P<0.001). Meanwhile, there were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between preoperation and at the last follow-up in the MS group ( Z=-16.52, -17.36; P<0.001). In the MS group, there were 61 (14.77%, 61/413), 306 (74.09%, 306/413), 27 (6.54%, 27/413) and 19 (4.60%, 19/413) cases of blepharospasm conditionally induced type, spasm type, reverse spasm type and oro-ocular elicited type, respectively. Conclusion:The electrophysiology of the ocular surface can objectively reflect the activity of periocular neuromuscular.

Objective To investigate the predictive value of pan-immune-inflammation value(PIV),blood urea nitrogen to albumin ratio(BAR),collateral circulation and National Institutes of Health stroke scale(NIHSS)score for disease progression and short-term prognosis in patients with acute perforating artery cerebral infarction(APACI).Methods Patients with APACI admitted to the Neurology Department of Anhui NO.2 Provincial People's Hospital from January 2019 to October 2024 were retrospectively enrolled in this study.General and clinical data,including age,gender,previous history(hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,drinking history,NIHSS scores at admission were collected.Fasting venous blood samples were collected from the patients within 24 h after admission to detect levels of neutrophils,lymphocytes,monocytes,platelets,blood urea nitrogen,and serum albumin.PIV(PIV=neutrophils × platelets × monocytes/lymphocytes)and BAR were calculated.The location of lesions and Fazekas classification of white matter lesions were evaluated using head MRI and MR angiography at admission.Collateral circulation status was assessed based on CT angiography upon admission.Disease progression was defined through comparing the NIHSS score at 72-hour after admission to the score at admission(an increase of 2 or more points in NIHSS score indicating disease progression).The patients were divided into a progression group and a non-progression group based on the increase in NIHSS score,as aforementioned.Patients follow-up was conducted through phone call or outpatient visits at 90 d after discharge.The modified Rankin scale(mRS)was used to evaluate the prognosis,with a mRS score of 0-2 indicates good prognosis,and a 3-6 indicates poor prognosis.Factors with statistically significant differences in univariate analysis were included in a multivariate Logistic regression analysis to explore the influencing factors of disease progression and poor prognosis in patients with APACI.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each indicator for disease progression and poor prognosis in patients with APACI.Results A total of 165 patients with APACI were enrolled in this study,including 121 males and 44 females,aged 27-86 years,with an average of(61±11)years.Among all patients enrolled,56 patients were included in the progression group and 109 patients in the non-progression group,124 patients showed good prognosis and 41 patients had poor prognosis.No statistically significant differences were found in age,gender,smoking history,drinking history,hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and Fazekas classification of white matter lesions between the progression group and the non-progression group(all P＞0.05).While the NIHSS score at admission,proportion of poor collateral circulation,PIV and BAR in the progression group were significantly higher than those in the non-progression group(all P＜0.05).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.177,95％CI 1.001-1.384,P=0.049),poor collateral circulation(OR,3.107,95％CI 1.216-7.939,P=0.018),high PIV(OR,1.006,95％CI 1.003-1.009,P=0.001),and high BAR(OR,1.610 × 109,95％CI 5.769 × 104-4.494 × 1013,P＜0.01)were independent risk factors of disease progression in patients with APACI.ROC curve analysis results showed that the area under the curve(AUC)of combination of PIV,BAR,collateral circulation and NIHSS score at admission for predicting disease progression in patients with APACI was 0.914(95％ CI0.861-0.952,P＜0.01),which was greater than that of each indicator(all P＜0.05).No statistically significant differences were found in smoking,drinking,hypertension,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and BAR between the poor prognosis and the good prognosis group(all P＞0.05).Compared with the good prognosis group,the poor prognosis group had significantly older age and higher proportion of patients with diabetes,NIHSS score at admission,proportion of patients with poor collateral circulation,and PIV(all P＜0.05).Moreover,the proportion of men in the poor prognosis group was lower than that in the good prognosis group(P=0.039).There was a statistically significant difference between the good prognosis group and the poor prognosis group in the Fazekas classification of white matter lesions(P＜0.01).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.345,95％CI 1.081-1.674,P=0.008),poor collateral circulation(OR,3.903,95％CI 1.061-14.355,P=0.040),and high PIV(OR,1.011,95％CI 1.005-1.017,P＜0.01)were independent risk factors of poor prognosis in patients with APACI.The AUC for predicting poor prognosis in patients with APACI through combining PIV,collateral circulation and NIHSS score at admission was 0.911(95％CI 0.857-0.950,P＜0.01),which is greater than using poor collateral circulation or NIHSS score at admission alone(both P＜0.05).However,there was no statistically significant difference in AUC between the PIV,collateral circulation and NIHSS score combined predictive model and the PIV(alone)predictive model(P＞0.05).Conclusions High PIV,high BAR,poor collateral circulation,and high NIHSS score at admission were independent risk factors of disease progression in patients with APACI.Combination of these four indices demonstrates relatively high predictive value for disease progression.In addition,high PIV,poor collateral circulation,and high NIHSS score at admission are independent risk factors of poor prognosis in patients with APACI.Joint detection of the three indices may assist in short-term prognosis evaluation of patients with APACI.

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