BACKGROUND:Belimumab, a monoclonal antibody targeting B lymphocyte stimulator, has shown benefits in systemic lupus erythematosus and lupus nephritis, but its role in IgA nephropathy (IgAN) remains unclear. We evaluated the effectiveness and safety of belimumab in IgAN. METHODS:This retrospective cohort study included biopsy-proven IgAN patients at Tongji Hospital, China (July 2020-June 2024). 69 patients treated with belimumab were compared with 137 propensity score-matched controls receiving standard therapy. The primary outcome was proteinuria remission, defined as a reduction in 24-hour urinary protein excretion or urine protein-to-creatinine ratio (UPCR) to < 50% of baseline. RESULTS:Among 206 patients with IgAN (median age 37 years, baseline eGFR 79 ml/min/1.73 m², proteinuria 1.1 g/24 h), 173 (84%) achieved proteinuria remission within 12 months. Remission was higher in the belimumab group: 59% vs 46% at 3 months, 77% vs 66% at 6 months, and 93% vs 80% at 12 months (P = 0.025 at 12 months), with lower time-averaged UPCR at 6 months [371 (248 738) vs.463(262 855) mg/g] and 12 months [360 (234 560) vs.433(243 720) mg/g, P = 0.066]. In newly diagnosed patients, remission was significantly higher at 3 months (76.5% vs. 47.1%, P = 0.009) and 6 months (88.2% vs. 67.6%, P = 0.045), with similar trends at later time points. In patients with baseline UPCR >600 mg/g and those receiving RAAS inhibitors, belimumab demonstrated comparable or superior proteinuria reduction. No excess of common adverse events was observed in the belimumab group. CONCLUSION:Belimumab treatment was associated with higher proteinuria remission rates in patients with IgAN, without an increased incidence of common adverse events. These findings suggest that belimumab may represent a superior therapeutic approach for IgAN in real-world clinical practice.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by cancer cells surrounded by affluent stromal components, which may underlie their limited response to various therapeutic interventions, including immunotherapy. Inflammatory cancer-associated fibroblasts (iCAFs), a crucial subset of CAFs within the PDAC microenvironment, play a pivotal role in shaping an immunosuppressive microenvironment. In this study, single-cell RNA sequencing analysis is performed to screen for cancer cells-secreted proteins associated with iCAF induction, and PPY (pancreatic polypeptide) is validated as a potent inducer. Unlike previously reported iCAF inducers, PPY is a gastrointestinal hormone predominantly expressed in the pancreas, suggesting that targeting it may have minimal systemic effects. Multiplex immunohistochemistry (mIHC) on human PDAC tissue microarrays, orthotopic allograft mouse models, and co-culture experiments are utilized to validate the crucial role of PPY in iCAF induction. Mechanistic studies integrating mRNA sequencing, immunoprecipitation-mass spectrometry, and molecular docking reveal that PPY induces iCAFs by activating the non-canonical NF-κB pathway through EGFR. Importantly, targeting PPY enhanced the efficacy of anti-PD-1 immunotherapy in KPC (KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx1-Cre) mice, as evidenced by reduced tumor burden on PET-CT imaging and improved survival. This research is expected to provide a novel strategy for improving immunotherapy in PDAC by targeting a key inducer of iCAFs.

Background Pancreatic ductal adenocarcinoma (PDAC) is characterized by a desmoplastic and immunosuppressive tumor microenvironment (TME), limiting the efficacy of immune checkpoint inhibitors such as anti-programmed cell death 1 (PD-1).Methods This study aimed to evaluate the therapeutic potential of Y126S, a recombinant IgG1/IgG2 hybrid bispecific antibody (BsAb), in reshaping the immunotherapy-resistant TME in PDAC. Orthotopic PDAC and KPC (KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx1-Cre) mouse models were established and treated with Y126S, α-connective tissue growth factor (CTGF), α-PD-1, or a combination of α-CTGF and α-PD-1. TME remodeling, antibody distribution, and therapeutic efficacy were assessed using flow cytometry, immunohistochemical/Masson staining, atomic force microscopy, positron emission tomography (PET) imaging, distribution analysis, and other experimental techniques.Results Here, Y126S was characterized in vitro and its antitumor efficacy was evaluated and validated in orthotopic PDAC mice and KPC mouse models. Notably, Y126S significantly remodeled the TME and demonstrated superior tumor-specific accumulation compared with single α-PD-1 treatment, leading to markedly enhanced antitumor efficacy relative to its parental antibodies or their combination. Mechanistically, Y126S suppressed cancer-associated fibroblasts (CAFs) activation, reduced collagen deposition, and downregulated programmed cell death ligand 1 (PD-L1) expression on CAFs by targeting CTGF and enhanced the anti-PD-1-mediated reinvigoration of cytotoxic CD8+ T cells, thereby establishing a less desmoplastic and potent tumor-killing microenvironment.Conclusions Our findings highlight the potential of Y126S as a promising BsAb-based immunotherapy strategy for PDAC by remodeling the desmoplastic and immunosuppressive TME.

Background Oncofetal reprogramming-the reactivation of fetal-like gene programmes in malignant cells-has been implicated in the progression and stemness of hepatocellular carcinoma (HCC), yet its protein landscape and connection to tumour stemness remain incompletely defined.Methods We integrated multi-omics datasets to derive an oncofetal reprogramming-based prognostic signature (oncoScore) and validated it across multiple independent HCC cohorts. Candidate oncofetal proteins were validated in murine fetal liver and HCC tissue microarrays. Functional characterization of dual-specificity phosphatase 9 (DUSP9) was performed using gain- and loss-of-function studies, including sphere and colony formation, proliferation, migration and invasion assays, sorafenib resistance testing, and limiting-dilution tumourigenicity assays. Mechanistic studies employed Oil Red O staining, co-immunoprecipitation, chromatin immunoprecipitation, pharmacologic inhibition and genetic rescue experiments.Results The oncoScore demonstrated robust prognostic value across multiple independent HCC cohorts. DUSP9 emerged as a key regulator of stemness, promoting self-renewal and aggressive phenotypes, enhancing sphere and colony formation, proliferation, migration, invasion, sorafenib resistance, and tumourigenicity. Mechanistically, DUSP9 drives lipid metabolism by upregulating stearoyl-CoA desaturase (SCD) through the ERK1/2peroxisome proliferator-activated receptor gamma (PPARG) signalling axis.Conclusion Our results establish the oncoScore as a reliable prognostic marker for HCC and identify a DUSP-9ERK1/2-PPARG-SCD pathway that links lipid metabolism to stemness. Targeting the oncofetal protein DUSP9 may offer a therapeutic avenue for aggressive, stemness-driven HCC.Key points Oncofetal reprogramming-based prognostic signature robustly stratifies HCC patient survival across independent cohorts. DUSP9 is identified as a core oncofetal regulator that drives stem-like traits in HCC. Mechanistically, DUSP9 suppresses ERK1/2-phosphorylation, stabilizes PPARG, and transcriptionally activates SCD. The DUSP9-ERK1/2-PPARG-SCD axis remodels lipid metabolism to support proliferation, cell mobility, and sorafenib resistance.

Cancer stem cells (CSCs) are strongly associated with the refractory characteristics of Hepatocellular carcinoma (HCC). However, the complex interaction between CSCs and the tumor microenvironment remains incompletely understood. In this study, we identified a novel long non-coding RNA (lncRNA) NEAT1 in cancer-associated fibroblast (CAFs)-derived extracellular vesicles (EVs) that play a critical role in the induction of CSCs and HCC tumorigenesis. NEAT1 was significantly overexpressed in human HCC tissues. Furthermore, high expression of lncRNA NEAT1 in EVs was found to be associated with poor prognosis. Knockdown of NEAT1 in CAFs inhibited invasion, migration, and tumor growth. Mechanistically, NEAT1 promoted cancer cell stemness, including 3D spheroid formation, by facilitating the liquid-liquid phase separation (LLPS) of the transcription factor YAP. Specifically, NEAT1 is directly bound to the intrinsic disordered region in the YAP protein, promoting the formation of LLPS biomolecular condensates. Additionally, a positive correlation between NEAT1 and Nanog was observed in clinical HCC tissues. In conclusion, our findings reveal that NEAT1 promotes HCC carcinogenesis and CSC induction by facilitating the LLPS of the YAP protein.

Cellular senescence plays a significant role in tumorigenesis and tumor progression. Substantial evidence indicates that senescence occurs in cancer-associated fibroblasts (CAFs), the predominant stromal component within the tumor microenvironment (TME), which profoundly impacts tumor biology. However, despite growing evidence of stromal cell involvement in cancer progression, the specific mechanisms and clinical implications of senescent CAFs (SCAFs) in hepatocellular carcinoma (HCC) have not been fully elucidated. The senescence signature was utilized to evaluate the senescence status of cell types within the TME of HCC using the GSE149614 dataset. The CytoTRACE and cell-cell communication analysis were used to find the correlation between cancer stemness and SCAFs. A risk prediction model associated with SCAFs was constructed to investigate potential mechanisms by which SCAFs promote tumor progression. Single-cell RNA sequencing data was used to identify senescent CAF-related genes. Gene expression and clinical data for HCC were obtained from the Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and National Omics Data Encyclopedia (NODE) databases. Using four machine-learning algorithms, crucial genes were identified to develop a CAF-senescence-related risk model, predicting prognosis, cancer stemness, immune infiltration, tumor mutation burden, and therapeutic responses in HCC patients. Next, we explored the role of Collagen Triple Helix Repeat Containing-1 (CTHRC1) in cancer stemness using both in vitro and in vivo experiments. Through various functional experiments, we elucidated the downstream signaling pathways of CTHRC1. Additionally, chromatin immunoprecipitation experiments were used to verify that key transcription factors bind to the CTHRC1 promoter region. CAFs exhibited high senescence status and a strong correlation with cancer stemness in HCC. A novel CAF-senescence-score (CSscore) prognostic model was established for HCC based on 10 genes: CTHRC1, SERPINE1, RNF11, ENG, MARCKSL1, ASAP1, FHL3, LAMB1, CD151, and OLFML2B. The survival prediction performance was validated on TCGA, ICGC, and NODE cohorts. Immune analysis revealed that the CSscore was positively correlated with immunosuppressive immune cell populations, including M2 macrophages and regulatory T cells. Conversely, a negative correlation was observed between the CSscore and anti-tumor immune cells such as CD8 + T cells, dendritic cells, and B cells HCC patients with a low CSscore had a lower tumor mutation burden and showed improved responsiveness to immunotherapy and transarterial chemoembolization. In vitro experiments and bioinformatics analysis further revealed that CTHRC1 was significantly elevated in SCAFs promoted cancer stemness and metastasis via the SRY-box transcription factor 4 (SOX4)-CTHRC1-Notch1 axis in HCC. Our study revealed that SCAFs were strongly correlated with cancer stemness in HCC. A novel machine learning model based on senescent CAF-related genes was constructed to accurately predict prognosis in HCC patients. Furthermore, CTHRC1 was identified as a novel prognostic and therapeutic biomarker to predict poor prognosis in HCC and promote cancer stemness and metastasis through the Notch signaling pathway, with its expression being transcriptionally regulated by SOX4.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of systemic small vasculitis characterized by the detection of ANCA in serum. Bactericidal permeability enhancing protein (BPI) is one of the target antigens of ANCA. BPI-ANCA-associated vasculitis is not common clinically, and the combination of bronchiectasis is not accidental. The paper reported a case of BPI-ANCA-associated vasculitis with renal damage combined with bronchiectasis. We reviewed relevant literature to explore the characteristics of BPI-ANCA-associated vasculitis and the correlation between bronchiectasis and ANCA-associated vasculitis, so as to improve the clinician's understanding on this disease.

格林-巴利综合征(Guillain-Barre syndrome,GBS)是一种免疫介导的多发性神经根神经病,常以急性或亚急性起病.发病率随着年龄的增长而增加且男性患病风险高于女性,全球发病率约为(1～2)/10万人[1-2].GBS可继发于感染或非感染性因素,超过 2/3的GBS患者在发病前 4周内有上呼吸道或消化道感染史[3].据报道,GBS病例中约30％的患者存在空肠弯曲菌感染,其他感染包括巨细胞病毒、肺炎支原体及戊型肝炎病毒.

Background The emergence of immune checkpoint inhibitors (ICIs) marks the beginning of a new era of immunotherapy for hepatocellular carcinoma (HCC), however, not all patients respond successfully to this treatment. A major challenge for HCC immunotherapy is the development of ways to screen for those patients that would benefit from this type of treatment and determine the optimal treatment plan for individual patients. Therefore, it is important to find a biomarker which allows for the stratification of HCC patients, which distinguishes responders from non-responders, thereby further improving the clinical benefits for those undergoing immunotherapy. Methods We used univariate and multivariate Cox risk proportional regression models to evaluate the relationship between non-synonymous mutations with a mutation frequency greater than 10%. We made a prognosis of an immunotherapy HCC cohort using mutation and prognosis data. An additional three HCC queues from the cbioportal webtool were used for further verification. The CIBERSORT, IPS, quanTIseq, and MCPcounter algorithms were used to evaluate the immune cells. PCA and z-score algorithm were used to calculate immune-related signature with published gene sets. Gene set enrichment analysis (GSEA) was used to compare the differences in the pathway-based enrichment scores of candidate genes between mutant and wild types. Results Univariate and multivariate Cox results showed that only CTNNB1-Mutant(CTNNB1-MUT) was associated with progression-free survival (PFS) of HCC patients in the immunotherapy cohort. After excluding the potential bias introduced by other clinical features, it was found that CTNNB1-MUT served as an independent predictor of the prognosis of HCC patients after immunotherapy (P < 0.05; HR > 1). The results of the tumor immune microenvironment (TIME) analysis showed that patients with CTNNB1-MUT had significantly reduced activated immune cells [such as T cells, B cells, M1-type macrophages, and dendritic cells (DCs)], significantly increased M2-type macrophages, a significantly decreased expression of immunostimulating molecules, low activity of the immune activation pathways (cytokine pathway, immune cell activation and recruitment) and highly active immune depletion pathways (fatty acid metabolism, cholesterol metabolism, and Wnt pathway). Conclusions In this study, we found CTNNB1-MUT to be a potential biomarker for HCC immunotherapy patients, because it identified those patients are less likely to benefit from ICIs.

目的探讨不同模式血液净化技术对肝功能衰竭患者疗效的评价。方法选取华中科技大学同济医学院附属同济医院接受血液净化治疗的肝功能衰竭患者,包括血浆置换（plasma exchange, PE）、PE+胆红素吸附及PE+双重血浆分子吸附（double plasma molecular adsorption system, DPMAS）3种模式,比较各组患者治疗前后总胆红素（total bilirubin, TBil）、直接胆红素、肝功能、肾功能、血红蛋白、血小板计数、凝血酶原时间（prothrombin time, PT）、活化部分凝血酶原时间（activated partial thromboplastin time, APTT）、国际标准化比值（international normalized ratio, INR）及终末期肝病模型（MELD）评分等的变化,比较各组之间的疗效,同时比较在不同模式下血浆及人血白蛋白用量对疗效的影响。结果 （1）治疗前后对比,在PE+DPMAS组,患者TBil、直接胆红素、天冬氨酸转氨酶（glutamic-oxaloacetic transaminase, GOT）、丙氨酸转氨酶（glutamic-pyruvic transaminase, GPT）、碱性磷酸酶、总蛋白、乳酸脱氢酶、尿素氮、血肌酐、血红蛋白、MELD评分明显降低、PT、APTT、INR明显增加,差异有统计学意义（P＜0.05）;在PE+胆红素吸附组,患者TBil、直接胆红素明显降低、白蛋白明显增加,差异有统计学意义（P＜0.05）;PE组患者TBil、直接胆红素治疗后有下降趋势;（2）3组模式组间比较,PE+DPMAS组TBil、直接胆红素、GOT、GPT、碱性磷酸酶、APPT、MELD评分下降更加明显、差异有统计学意义（P＜0.05）;（3）PE+胆红素吸附组补充白蛋白量和胆红素下降率呈负相关（r=-0.34,P=0.02）,具有统计学意义。结论 3种不同血液净化模式均可不同程度改善患者肝功能;3种模式比较,PE+DPMAS组在改善肝功能方面高于PE组和PE+胆红素吸附组;PE+胆红素吸附组治疗过程中,患者补充白蛋白越多,胆红素下降越明显。

Blood brain barrier (BBB) disruption plays an important role in brain injury after acute kidney injury (AKI). However, its underlying mechanisms remain poorly understood. Recent evidence has revealed that proper mitochondrial function is essential for BBB permeability. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a key factor in mitochondrial biogenesis and function. This study was designed to investigate the role of PGC-1α in BBB injury after AKI and its related mechanisms. Mice received recombinant adenovirus encoding murine PGC-1α (100 μl, 1.0 × 109PFU/ml) or vehicle 5 days before renal I/R or sham operation. Twenty-four hours after the operation, brain, kidney and serum samples were collected for assessments. We found that mice suffering from renal I/R injury showed decreased PGC-1α levels in both the kidney and BBB. PGC-1α transfection resulted in increased PGC-1α level and mitochondrial transcripts in BBB at 24 h after AKI. PGC-1α transfection improved renal function, systemic inflammation and BBB permeability via both the paracellular and transcellular pathways. Further study suggested that PGC-1α overexpression elevated fatty acid oxidation related gene expression. Our findings demonstrate the importance of PGC-1α in AKI-induced BBB injury and suggest that it could be a therapeutic target for BBB repair via the regulation of mitochondrial function.

Introduction: Erbin is ubiquitously expressed in normal epithelial tissues and localizes at the basolateral membrane to regulate cell junctions and polarity in epithelial cells. However, the function of Erbin in hepatocelllular carcinoma progression is controversial. In this study, we investigated the role of Erbin in carcinogenesis. Method: we first detected the expression of Erbin in HCC and adjacent tissues; Stable Erbin-knockdown and Erbin-overexpression HCC cell line were established, then cell proliferation were detected in vitro and in vivo. The effect of smad dependent pathway and ERK pathway in Erbin induced proliferation in HCC cells were detected. Result: Erbin expression in HCC tissues was increased markedly compared with their adjacent liver tissues. Overexpression Erbin enhance the proliferation of HCC cells in vitro and in vivo. Overload erbin suppressed TGF-beta - smad pathway and down regulated CDK inhibitor p21 and p27, which are negative regulator of cell cycle. Knock down Erbin suppressed proliferation of HCC cells in vitro and in vivo. Disintegrating TGF-beta-samd dependent pathway by TGFR inhibitors or down regulation of smad4 could cripple the anti-proliferation effect in HCC cells. Conclusion: Erbin promotes HCC cells proliferation through inhibiting TGFβ-samds pathway and downregulating p21 and p27

Objective To explore the mechanism,curative effect and existing problems of rituximab therapyforpatientswith refractory nephrotic syndrome through analysis of 2 typical cases and literature review.Methods The clinical characteristics and effects of low dose rituximab for two patients with refractory nephrotic syndrome were retrospectively analyzed and the related literatures were reviewed.Results Case 1 was diagnosed as stage Ⅱ membranous nephropathy by renal biopsy.Glucocorticoids and commonly used immunosuppressants (cyclophosphamide,tacrolimus,mycophenolatemofetil) had poor efficacy and the disease could not be alleviated.After administration of rituximab (100 mg) permonth for 3 months,serum albumin was significantly elevated,serum creatinine was decreased,eGFR was increased,urinary protein was significantly reduced,and patient achieved partial remission.Case 2 given glucocorticoid in combination with mycophenolatemofetil,cyclophosphamide andtacrolimus could be relieved,but frequent relapses occurred during drugs reduction.Complete remission could be achieved after a single rituximab (100mg) treatment.The albumin level increased to the normal level,and urinary protein turned negative.There was no obvious adverse reaction during the treatment.Conclusions Low dose rituximab is a safe and effective treatment for refractory nephrotic syndrome.

The problems in practice teaching of physical diagnosis for student abroad of MBBS are lack of unified textbook,obstacles in language communication,difference of cultural backgrounds and indiscipline.Teachers should improve their English skills and professional knowledge level,strengthen the management of the student abroad.According to the characteristics of the student abroad of MBBS,the teachers should choose multiple teaching methods and testing model.All these methods are used to raise MBBS teaching quality.

Renal tubulointerstitial fibrosis is the common ending of progreβsive renal disease. It is worth developing new ways to stop the progreβs of renal fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been studied to treat diabetic nephropathy, cisplatin-induced acute renal injury, ischemia reperfusion injury and adriamycin nephropathy. In this study, unilateral ureteral obstruction (UUO) was used to establish a different renal fibrosis model. PPAR? agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14th day after the operation, mice were sacrificed for fibrosis test and T lymphocytes subsets test. Unexpectedly, through MASSON staining, immunohistochemistry for α-SMA, and Western blotting for a-SMA and PDGFR-β, we found that pioglitazone failed to attenuate renal fibrosis in UUO mice. However, flow cytometry showed that pioglitazone down-regulated Th1 cells, and up-regulated Th2 cells, Th17 cells and Treg cells. But the Th17/Treg ratio had no significant change by pioglitazone. Real-time PCR results showed that TGF-β and MCP-1 had no significant changes, at the same time, CD4+ T cells associated cytokines were partially regulated by pioglitazone pretreatment. Taken together, pioglitazone failed to suppress renal fibrosis progression caused by UUO.

Objective To investigate the expression of ErbB2 interacting protein (Erbin) in renal ischemia-reperfusion injury (IRI) in vivo and in vivo,and the effect of Erbin over-expression on IRI.Methods (1) In vivo,the model of renal IRI was constructed in mice,and set up sham group and reperfusion 3,6,12,24 and 48 h IRI group.BUN and Scr were detected and PAS staining was used to observe the pathology change of renal tissues.Cell apoptosis was detected by TUNEL staining.Erbin and NF-κB expression in renal tissue was detected by Western blotting,and immunohistochemistry was used to detect the distribution of Erbin.(2) In vivo,IRI model in HK2 cells was constructed and cells were harvested after culturing in normal medium for 3,6,12 and 24 h.Erbin expression was detected by Western blotting.Flow cytometry and ELISA were used to evaluate the level of cell apoptosis and inflammatory cytokine secretion respectively.HK2 cells were transiently transfected with Prk5-myc-Erbin plasmid via lipofectamine 2000,and were divided into control group,IRI group,Erbin group and Erbin + IRI group.The protein expression of Erbin and NF-κB,cell apoptosis and inflammatory cytokine secretion was detected.Results (1) Compared with sham group,serum BUN and Scr were dramatically increased in IRI model,especially in 24 h after reperfusion (P ＜ 0.05).Moreover,PAS staining showed that a lot of renal tubular epithelial cells were necrosis and fell off,and many protein cast were formed,renal injury score and apoptotic index were higher in 6 h,12 h,24 h,48 h IRI model than those in sham group (all P ＜ 0.05).The expression of Erbin,which was expressed in renal tubules,and nuclear NF-κB in 24 h IRI model were significantly increased,as compared with sham group (all P ＜ 0.05).(2) Compared to those in control group,nuclear NF-κB expression,apoptosis and inflammatory cytokine secretion were significantly increased in IRI group.Meanwhile,Erbin expression was also induced and peaked at 24 h (P ＜ 0.05).Compared to those in IRI group,cell apoptosis,the expression of nuclear NF-κB,inflammatory cytokine IL-6 and TNF-α were decreased in Erbin+IRI group (all P ＜ 0.05).Conclusions Erbin expression is up-regulated in renal IRI,and over-expression of Erbin can partly inhibit NF-κB activation,cell apoptosis and inflammatory cytokine secretion in IRI group,which indicates Erbin may playing a protective role in renal IRI.

Grape seed proanthocyanindin extract (GSPE) is a polyphenolic bioflavonoid derived from grape seeds and has been widely studied for its potent antioxidant, anti-inflammatory and antitumor activities. HMGB1 is a newly discovered danger-associated molecular pattern (DAMP) that has potent proinflammatory effects once released by necrotic cells. However, the effect of GSPE on the HMGB1, and the relationship of those two with acute kidney injury and chronic kidney fibrosis are unknown. This study aimed to investigate the impact of GSPE on acute kidney injury and chronic fibrosis. C57bl/6 mice were subjected to bilateral ischemia/reperfusion (I/R) and unilateral I/R with or without GSPE administration. After bilateral I/R, mice administered GSPE had a marked improvement in renal function (BUN and Cr), decreased pathological damage and reduced inflammation. In unilateral I/R, mice subjected GSPE showed reduced tubulointerstitial fibrosis and decreased inflammatory reaction. The renoprotection of GSPE on both models was associated with the inhibition of HMGB1 nucleocytoplasmic shuttling and release, which can amplify the inflammation through binding to its downstream receptor TLR4 and facilitated P65 transcription. Thus, we have reason to believe that GSPE could be a good alternative therapy for the prevention and treatment of IR-induced renal injury and fibrosis in clinical practice.