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 assess the value of magnetic resonance imaging compilation(MAGiC)sequence in predicting lympho-vascular space invasion(LVSI)in early cervical cancer.Methods The data of 48 patients with cervical cancer confirmed by pathology were collected retrospectively,and classified into LVSI-positive group(n=29)and LVSI-negative group(n=19)according to postop-erative pathological results.MAGiC sequence images of patients were obtained before injecting contrast agents,then the region of interest(ROI)was delineated along the largest dimension edge of the lesion,and T1,T2 and proton density(PD)values were automatically generated by the software.Predictors were screened by univariate analysis and receiver operating characteristic(ROC)curves were drawn to assess their diagnostic efficacy for predicting LVSI in cervical cancer.Results Significant differences were found in T1 and PD values between LVSI-positive and LVSI-negative groups(P=0.003,P=0.017).There were no significant differences in T2 values between the two groups(P=0.414).The area under the curve(AUC)for T1 and PD values to predict LVSI status were 0.73 and 0.721,respectively.Conclusion LVSI-positive group of cervical cancer has lower T1 and PD values than LVSI-negative group based on MAGiC sequence.The MAGiC sequence has a certain application value for predicting LVSI status in early cervical cancer.

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.

Objective To investigate the clinical value of MRI in the diagnosis of oblique vaginal septum syndrome(OVSS),and to improve the diagnostic level for this disease.Methods Clinical and imaging data of 8 patients (7 adolescent females and 1 female in fertility period)with vaginal septum syndrome were analyzed retrospectively.All participants were evaluated by ultrasound examination before MRI scanning,and 1 of them underwent enhanced MRI scan.Results Among the 8 patients with OVSS,the main findings of MRI includes uterine deformity (4 double uterus,3 mediastinal uterus,1 double angle uterus with uterine septum),oblique vaginal septum (7 right oblique septum and 1 left oblique septum).All subjects presented with ipsilateral renal agenesis,and 4 patients with endometriosis,1 patient with ureteral distortion and ectopic opening and 1 patient with double inferior vena cava.6 patients suffered with hemorrhage in the posterior chamber of oblique septum and 2 patients with empyema.Hemorrhage in the contralateral vagina were observed in 3 cases,while no significant abnormality was found in other 5 cases.Conclusion MRI scan has an important clinical value on the diagnosis of OVSS and can provide crucial information for the optimal individual treatment.

Objective To investigate the value of serum cholinesterase (S-ChE) levels in judgment of severity and prognosis in patients with severe pneumonia. Methods The clinical data of patients with severe pneumonia, who were admitted to the Department of Internal Medicine in the First Affiliated Hospital of Sun Yat-sen University, or the Department of Neurology in the Third People's Hospital of Foshan from May 2011 to May 2015, whose hospital time was longer than 24 hours, were retrospectively analyzed. They were divided into survival group and death group according to the final outcome. Lab data, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, multiple organ dysfunction syndrome (MODS) score, the improved pneumonia score of British Thoracic Society (confusion, uremia, respiratory, blood pressure, age 65 years, CURB-65), and S-ChE levels of all patients were collected after they were hospitalized into the intensive care unit (ICU) within 24 hours. Independent risk factors for prognosis were analyzed by binary logistic regression analysis, and receiver operating characteristic curve (ROC) was plotted. Best truncation point analysis was used to compare their estimated value for prognosis of patients with severe pneumonia. Results Eighty-six patients with severe pneumonia were studied. Among them 46 patients survived, and 40 patients died. By the single factor analysis, the following lab data in the death group were found significantly lower than those in the survival group: S-ChE levels (kU/L: 2.748±0.826 vs. 4.489±1.360, t' = 7.274, P = 0.000), arterial partial pressure of oxygen [PaO2 (mmHg, 1 mmHg = 0.133 kPa): 52.55±18.29 vs. 60.83±16.65, t = 2.196, P = 0.031], oxygenation index (mmHg: 114.20±48.01 vs. 167.10±69.68, t' = 4.229, P = 0.000), and carbon dioxide combining power [CO2-CP (mmol/L): 22.85±5.44 vs. 26.00±7.63, t' = 2.225, P = 0.029]. The following clinical data were significantly higher in the death group than those in the survival group, namely body temperature (℃: 38.67±1.18 vs. 37.74±1.18, t = -3.627, P = 0.000), pulse (bpm: 130.65±15.72 vs. 107.26±19.61, t' = -6.133, P = 0.000), the ratio of concomitant chronic lung disease [45.0% (18/40) vs. 13.0% (6/46), χ2 = 10.860, P = 0.001], fraction of inspired oxygen [FiO2: 0.495 (0.410, 0.600) vs. 0.380 (0.290, 0.500), Z = -3.265, P = 0.001], APACHE Ⅱ score (25.80±5.07 vs. 16.39±5.12, t =-8.540, P = 0.000), CURB-65 score [3 (3, 4) vs. 2 (1, 2), Z = -5.562, P = 0.000], MODS score (8.15±2.49 vs. 4.35±2.01, t = -7.832, P = 0.000), international normalized ratio [INR: 1.22 (1.08, 1.31) vs. 1.07 (1.00, 1.10), Z = -4.231, P = 0.000], and activated partial thromboplastin time [APTT (s): 33.80 (32.13, 38.75) vs. 28.50 (25.70, 36.00), Z = -3.482, P = 0.000]. Binary logistic regression analysis showed that, S-ChE levels, APACHE Ⅱ score and MODS score were found to be the independent risk factors for prognosis in the patients with severe pneumonia, respectively [S-ChE: odds ratio (OR) = 0.084, 95% confidence interval (95%CI) = 0.017-0.424, P = 0.003; APACHE Ⅱ score: OR = 1.675, 95%CI = 1.098-2.556, P = 0.017; MODS score: OR = 2.189, 95%CI = 1.262-3.800, P = 0.005]. The area under ROC (AUC) for S-ChE levels, APACHE Ⅱ score and MODS score were 0.874±0.036, 0.889±0.033 and 0.884±0.035, respectively (all P > 0.05 as compared between any two means). At the best truncation points of S-ChE levels, APACHE Ⅱ score and MODS score were 3.372 kU/L, 19.5 score, and 6.5 score respectively. The sensitivity, specificity, positive predictive value and negative predictive value in predicting death risk in patients with severe pneumonia were (80.0%, 78.0%, 76.19% and 81.82%), (95.0%, 70.0%, 73.08% and 94.12%) and (70.0%, 91.0%, 87.50%, 77.78%), respectively. If S-ChE levels was combined with APACHE Ⅱ score or combined with MODS score, the sensitivity, specificity, positive predictive value and negative predictive value [S-ChE levels combined APACHE Ⅱ score: 100%, 92.0%, 93.75% and 100%; S-ChE levels combined MODS score: all 100%] were higher than single power of S-ChE levels, APACHE Ⅱ score or MODS score. Conclusions S-ChE levels can be considered as an effective and practical index to estimate the severity and prognosis in patients with severe pneumonia. The combined application of S-ChE levels and APACHE Ⅱ score or MODS score can obviously improve the prognostic power in patients with severe pneumonia.

Objective To study the multi-slice helical CT (MSCT) features of horseshoe lung and to improve its diagnostic ability. Methods The clinical and imaging data were retrospectively reviewed in 5 patients. All of them underwent plain MSCT scan, and 4 patients also had enhanced MSCT scan and threedimensional reconstruction. Results In horseshoe lung, the basal segments of the right and left lungs were fused together by a isthmus of pulmonary parenchyma, across the midline behind the pericardium and before the esophagus, descending aorta and spine. All patients were companied with bronchopulmonary dysplasia,anomalous origin of the central bronchi, anomalous arterial supply. Anomalous pulmonary venous return to inferior vena cava and congenital cardiovascular malformations were also found in 4 cases. Conclusion MSCT and three-dimensional reconstruction are valuable for identification of horseshoe lung.

Objective To observe the mRNA and protein expression of SOCS-1 and SOCS-3 in the peripheral blood mononuclear cells(PBMCs) in patients with systemic inflammatory response syndrome(SIRS) and explore its clinical significance.Methods Peripheral blood of 20 patients with SIRS and 16 healthy people wag collected and the PBMCs were isolated by centrifugafion and Ficoll-Hypaque sedimentation.The mRNA of SOCS-1 and SOCS-3 was determined by reverse transcription-polymerase chain reaction(RT-PCR).And the protein content of SOCS-1 and SOCS-3 was determined by Western Blotting.Results The SOCS-1 mRNA expression in the PBMCs of SIRS group (0.642±0.112) was significant higher than that of control group(0.458±0.044)(P<0.05).There was no significant difference between the PBMCs,SOCS-1 content of control group(0.488±0.019) and SIRS group (0.471±0.041).The SOCS-3 mRNA expression in the PBMCs of SIRS group(0.989±0.324) was higher than that control group(0.459±0.046)(P<0.05).There was no significant difference between the PBMCs'SOCS-3 content of control group(0.400±0.025) and SIRS group(0.426±0.015).Conclusions The mRNA expression of SOCS-1 and SOCS-3 in the PBMCs were higher in SIRS patients.The SOCS-1 and SOCS-3 may participate in the development of SIRS.