OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

Objective To explore the mechanism of IgA nephropathy(IgAN)caused by multi-glycosides of Tripterygium wilfordii(GTW)through the regulation of Silent information regulatory factor 1(SIRT 1)/nuclear transcription factor E2-related factor 2(Nrf 2)/antioxidant enzyme heme oxygenase 1(HO-1)signaling pathway.Methods Forty-five male SD rats were selected and randomly divided into two groups:the blank group(n=9)and the model group(n=36).In addition to the blank group,the BSA+CCl4+LPS group was used.At the end of 12 weeks,two rats were randomly selected for verification,and the model was successfully established.The 34 model rats were randomly divided into 3 groups:the model group(n=10),prednisone group(n=12),and GTW group(n=12).Urine,blood and kidney tissues were harvested 4 weeks after drug administration.Urinary erythrocyte number,24-h urinary protein quantification(24 h-UTP),alanine transaminase(ALT),serum albumin(ALB),urea nitrogen(BUN),and blood creatinine(SCr)were performed for each group;the protein expression of SIRT1,Nrf2,HO-1 and PINK1 was detected by Western blotting analysis;real-time polymerase chain reaction(RT-PCR)detection of SIRT1,Nrf2,HO-1 and PINK1 mRNA expression in rat kidney tissue;and detection of IgA deposition in the renal mesangial area by immunofluorescence.Kidney histopathological changes were observed in all the rats by hematoxylin-eosin(HE)staining.Results The results compared with those in the blank group,the urinary red blood cell count and 24 h-UTP,ALT,BUN,and SCr levels were significantly greater(P<0.01);The ALB level was significantly lower(P<0.01);renal tissue SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly lower(P<0.01);IgA deposition in the mesentery was obvious;renal pathological damage was severe;and the difference was statistically significant. Compared with those in the model group,urinary red blood cell counts and 24 h-UTP,ALT,BUN,and SCr levels in the prednisone and GTW groups were significantly lower (P<0.01);ALB levels were significantly greater (P<0.01);SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly greater (P<0.01);IgA deposition in the mesangial area was reduced,and renal pathology was improved,with statistically significant difference. Conclusions GTW may alleviate oxidative stress injury,protect renal function,and improve renal injury by activating the SIRT 1/Nrf 2/HO-1 signaling pathway.

Objective To explore the mechanism of IgA nephropathy(IgAN)caused by multi-glycosides of Tripterygium wilfordii(GTW)through the regulation of Silent information regulatory factor 1(SIRT 1)/nuclear transcription factor E2-related factor 2(Nrf 2)/antioxidant enzyme heme oxygenase 1(HO-1)signaling pathway.Methods Forty-five male SD rats were selected and randomly divided into two groups:the blank group(n=9)and the model group(n=36).In addition to the blank group,the BSA+CCl4+LPS group was used.At the end of 12 weeks,two rats were randomly selected for verification,and the model was successfully established.The 34 model rats were randomly divided into 3 groups:the model group(n=10),prednisone group(n=12),and GTW group(n=12).Urine,blood and kidney tissues were harvested 4 weeks after drug administration.Urinary erythrocyte number,24-h urinary protein quantification(24 h-UTP),alanine transaminase(ALT),serum albumin(ALB),urea nitrogen(BUN),and blood creatinine(SCr)were performed for each group;the protein expression of SIRT1,Nrf2,HO-1 and PINK1 was detected by Western blotting analysis;real-time polymerase chain reaction(RT-PCR)detection of SIRT1,Nrf2,HO-1 and PINK1 mRNA expression in rat kidney tissue;and detection of IgA deposition in the renal mesangial area by immunofluorescence.Kidney histopathological changes were observed in all the rats by hematoxylin-eosin(HE)staining.Results The results compared with those in the blank group,the urinary red blood cell count and 24 h-UTP,ALT,BUN,and SCr levels were significantly greater(P<0.01);The ALB level was significantly lower(P<0.01);renal tissue SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly lower(P<0.01);IgA deposition in the mesentery was obvious;renal pathological damage was severe;and the difference was statistically significant. Compared with those in the model group,urinary red blood cell counts and 24 h-UTP,ALT,BUN,and SCr levels in the prednisone and GTW groups were significantly lower (P<0.01);ALB levels were significantly greater (P<0.01);SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly greater (P<0.01);IgA deposition in the mesangial area was reduced,and renal pathology was improved,with statistically significant difference. Conclusions GTW may alleviate oxidative stress injury,protect renal function,and improve renal injury by activating the SIRT 1/Nrf 2/HO-1 signaling pathway.

Pediatric lupus nephritis(LN),the most severe visceral complication of systemic lupus erythematosus,is characterized by hematuria,proteinuria,and progressive renal dysfunction.It typically presents with an insidious onset,rapid progression,a prolonged disease course,and an unfavorable long-term prognosis.Currently,no consensus exists on the etiology,pathogenesis,or diagnostic-treatment framework for pediatric LN.Based on clinical experience,the proposed core pathogenesis involves"latent pathogens in the triple energizer membrane system with deficiency-induced toxin activation."This mechanism entails the intermingling of heat and blood stasis,forming pathogenic factors that lodge within the triple energizer membrane system.In states of healthy qi deficiency,internal and external factors interact,allowing pathogenic toxins to damage the viscera via the triple energizer membrane network,ultimately targeting the kidneys.The disease progression is classified into three distinct phases.In the latent pathogen phase,internal or external pathogens accumulate in the triple energizer membrane system.Treatment emphasizes pathogen elimination,heat clearance,and healthy qi preservation.In the active renal involvement phase,latent pathogens rapidly disseminate systemically via the membrane network,destabilizing renal essence and causing micro-substance leakage.Treatment focuses on toxin resolution,stasis dispersion,membrane regulation,and renal stabilization.During the triple energizer residual phase,incomplete restoration of healthy qi permits the persistence of dormant pathogens,predisposing to reactivation.Therapeutic focus during this phase includes qi consolidation to restore primordial essence,residual pathogen clearance,and mitigating disease recurrence to delay chronic renal deterioration.This phase-specific differentiation-treatment strategy aims to address disease complexity while optimizing therapeutic outcomes through targeted interventions.

Objective To investigate the mechanism of improving renal injury in rats with diabetic nephropathy(DN)by Yiqi Yangyin Huoxue Formula.Methods Male SD rats were fed with high-fat and high-sugar diet,combining with a single in-traperitoneal injection of streptozotocin to establish DN model.The rats were divided into the model group,the valsartan group,the equal-dose group of Yiqi Yangyin Huoxue Formula(equal-Yi group),and the high-dose group of Yiqi Yangyin Huoxue For-mula(high-Yi group)according to the method of randomized numerical table.The treatment groups were administered by gavage from the tenth week of the modeling period.Levels of 24-hour urinary total protein(UTP),blood urea nitrogen(BUN),serum creatinine(SCr),glucose(GLU),cholesterol(CHOL),and triglycerides(TG)were measured.Serum malondialdehyde(MDA)lev-els were detected by ELISA.Western blot was used to detect the protein expression of XBP1,HRD1,Nrf2,SLC7A11,and GPX4 in rat kidney tissues.The qRT-PCR was used to detect the mRNA expression levels of XBP1,HRD1,Nrf2,SLC7A11,and GPX4 in rat kidney tissues.HE staining was used to observe the pathological changes in the kidney tissues of rats in each group.Results Compared with the blank group,rats in the model group showed significantly higher levels of 24h-UTP,BUN,SCr,GLU,CHOL,and TG(all P＜0.01),significantly higher levels of serum MDA(P＜0.01),significantly higher expression of XBP1,HRD1 protein and mRNA in renal tissues(all P＜0.01),significantly lower protein and mRNA expression of Nrf2,SLC7A11,and GPX4(all P＜0.01),and renal pathological damage was severe.Compared with the model group,24h-UTP,BUN,SCr,GLU,CHOL,TG levels were significantly reduced in the valsartan group,equal-Yi group and high-Yi group(all P＜0.01),serum MDA levels were significantly reduced(P＜0.01),XBP1,HRD1 protein and mRNA expressions in renal tissues were significantly reduced(all P＜0.01),Nrf2,SLC7A11,GPX4 protein and mRNA expression were significantly increased(all P＜0.01),and renal pathology was improved.Conclusion Yiqi Yangyin Huoxue Formula may inhibit the occurrence of endo-plasmic reticulum stress,attenuate iron death injury,protect renal function and ameliorate renal injury by regulating XBP1/HRD1/Nrf2 signaling pathway.

Tripterygium wilfordii multiglucoside,the primary active constituent of the Chinese materia medica of Tripterygium wilfordii,has anti-inflammatory and immune-regulation properties and is widely used to treat kidney and rheumatic and immunological diseases.However,the potential adverse effects of Tripterygium wilfordii multiglucoside on pediatric gonadal development have limited its clinical application in pediatrics.According to the traditional Chinese medicine theory,the reproductive toxicity of Tripterygium wilfordii is closely associated with deficiency in kidney essence and tian gui disorder.Based on the"kidney essence-tian gui"theory,this study elucidates the transformation of"kidney essence to tian gui"through the qi transformation of"original noumenon to supreme ultimate,"which is synergistically regulated by the accumulation of kidney qi,consolidation of spleen qi,and conveyance and dispersion of liver qi.It is channeled through the interconnected pathways of the thoroughfare channel,conception channel,and governor channel.The physiological process of"kidney essence to tian gui"is damaged by the bitter,cold,and toxicity of Tripterygium wilfordii,leading to kidney asthenia,spleen deficiency,liver depression,and meridian stagnation,causing tian gui dysregulation.Therefore,this study offers traditional Chinese medicine prevention and treatment strategies for pediatric medication safety,including nourishing the kidney essence to replenish the tian gui source,enhancing the middle jiao to strengthen the tian gui guard,regulating liver qi to promote the operation of tian gui,and unblocking the thoroughfare channel,conception channel,and governor channel to ensure the unobstructed pathway of tian gui.

Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.

Objective To investigate the mechanism of improving renal injury in rats with diabetic nephropathy(DN)by Yiqi Yangyin Huoxue Formula.Methods Male SD rats were fed with high-fat and high-sugar diet,combining with a single in-traperitoneal injection of streptozotocin to establish DN model.The rats were divided into the model group,the valsartan group,the equal-dose group of Yiqi Yangyin Huoxue Formula(equal-Yi group),and the high-dose group of Yiqi Yangyin Huoxue For-mula(high-Yi group)according to the method of randomized numerical table.The treatment groups were administered by gavage from the tenth week of the modeling period.Levels of 24-hour urinary total protein(UTP),blood urea nitrogen(BUN),serum creatinine(SCr),glucose(GLU),cholesterol(CHOL),and triglycerides(TG)were measured.Serum malondialdehyde(MDA)lev-els were detected by ELISA.Western blot was used to detect the protein expression of XBP1,HRD1,Nrf2,SLC7A11,and GPX4 in rat kidney tissues.The qRT-PCR was used to detect the mRNA expression levels of XBP1,HRD1,Nrf2,SLC7A11,and GPX4 in rat kidney tissues.HE staining was used to observe the pathological changes in the kidney tissues of rats in each group.Results Compared with the blank group,rats in the model group showed significantly higher levels of 24h-UTP,BUN,SCr,GLU,CHOL,and TG(all P＜0.01),significantly higher levels of serum MDA(P＜0.01),significantly higher expression of XBP1,HRD1 protein and mRNA in renal tissues(all P＜0.01),significantly lower protein and mRNA expression of Nrf2,SLC7A11,and GPX4(all P＜0.01),and renal pathological damage was severe.Compared with the model group,24h-UTP,BUN,SCr,GLU,CHOL,TG levels were significantly reduced in the valsartan group,equal-Yi group and high-Yi group(all P＜0.01),serum MDA levels were significantly reduced(P＜0.01),XBP1,HRD1 protein and mRNA expressions in renal tissues were significantly reduced(all P＜0.01),Nrf2,SLC7A11,GPX4 protein and mRNA expression were significantly increased(all P＜0.01),and renal pathology was improved.Conclusion Yiqi Yangyin Huoxue Formula may inhibit the occurrence of endo-plasmic reticulum stress,attenuate iron death injury,protect renal function and ameliorate renal injury by regulating XBP1/HRD1/Nrf2 signaling pathway.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Tripterygium wilfordii multiglucoside,the primary active constituent of the Chinese materia medica of Tripterygium wilfordii,has anti-inflammatory and immune-regulation properties and is widely used to treat kidney and rheumatic and immunological diseases.However,the potential adverse effects of Tripterygium wilfordii multiglucoside on pediatric gonadal development have limited its clinical application in pediatrics.According to the traditional Chinese medicine theory,the reproductive toxicity of Tripterygium wilfordii is closely associated with deficiency in kidney essence and tian gui disorder.Based on the"kidney essence-tian gui"theory,this study elucidates the transformation of"kidney essence to tian gui"through the qi transformation of"original noumenon to supreme ultimate,"which is synergistically regulated by the accumulation of kidney qi,consolidation of spleen qi,and conveyance and dispersion of liver qi.It is channeled through the interconnected pathways of the thoroughfare channel,conception channel,and governor channel.The physiological process of"kidney essence to tian gui"is damaged by the bitter,cold,and toxicity of Tripterygium wilfordii,leading to kidney asthenia,spleen deficiency,liver depression,and meridian stagnation,causing tian gui dysregulation.Therefore,this study offers traditional Chinese medicine prevention and treatment strategies for pediatric medication safety,including nourishing the kidney essence to replenish the tian gui source,enhancing the middle jiao to strengthen the tian gui guard,regulating liver qi to promote the operation of tian gui,and unblocking the thoroughfare channel,conception channel,and governor channel to ensure the unobstructed pathway of tian gui.