Objective To compare the efficacy and safety of flexible ureteral lithotripsy(FURL)and non-retrograde percutaneous nephrolithotomy(NR-PCNL)for treating1.5-2.0 cm upper ureteral stones.Methods We retrospectively analyzed clinical data of 130 patients with upper ureteral stones treated between October 2022 and October 2024.Sixty-two patients underwent FURL and 68 underwent NR-PCNL.Comparisons included operative time,pre-and postoperative changes in white blood cells(WBC),hemoglobin(Hb),and creatinine(Cr),postoperative C-reactive protein(CRP)levels,stone-free rate after primary surgery,postoperative hospitalization duration,pain scores,complications,and need for auxiliary treatments.Results Compared to the FURL group,the NR-PCNL group demonstrated advantages in operative time[54.0(44.3,69.3)min vs.82.5(66.0,101.0)min,Z=-5.565,P<0.001],WBC elevation[1.9(0.5,3.5)×109/L vs.4.5(3.0,6.0)×109/L,Z=-4.528,P<0.001],and secondary surgery rate[0%(0/68)vs.14.5%(9/62),P<0.001].The FURL group showed lower Hb reduction[3.0(2.0,6.3)g/L vs.8.0(5.0,11.0)g/L,Z=-4.262,P<0.001],less postoperative Visual Analogue Scale(VAS)pain scores[1.0(1.0,2.0)points vs.2.0(1.0,2.0)points,Z=-2.840,P=0.005],and shorter hospitalization duration[2.0(1.0,2.0)d vs.3.0(2.0,3.0)d,Z=-5.815,P<0.001].No significant differences were observed in Cr elevation,CRP levels,stone-free rate after primary surgery,complications,or analgesic requirements(P≥0.05).Conclusions Both NR-PCNL and FURL are safe and effective for 1.5-2.0 cm upper ureteral stones.FURL offers better patient comfort,while NR-PCNL shows superior overall safety.

Objective To observe the effects of Bushen Huoxue Prescription on the pathway related to necroptosis of nucleus pulposus cells in a model rabbit of intervertebral disc degeneration;To explore its mechanisms in delaying intervertebral disc degeneration.Methods A intervertebral disc degeneration rabbit model was established using the spinal instability method.Totally 40 model rabbits were randomly divided into model group,ibuprofen group and Bushen Huoxue Prescription low-,medium-and high-dosage groups.Additionally,a normal control group and a sham-operation group were set up,with 8 rabbits in each group.Each treatment groups received the corresponding drugs via gavage for two consecutive weeks.HE staining was used to observe morphology of nucleus pulposus tissue,transmission electron microscopy was used to observe ultrastructure in nucleus pulposus cells,immunohistochemical staining was used to assess the expressions of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue,Western blot was used to detect the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus tissue.Results Compared with the sham-operation group,the model group showed a significant decrease in nucleus pulposus cells,disordered cell arrangement,reduced extracellular matrix,interrupted cell membrane continuity under transmission electron microscopy,organelle swelling,nuclear membrane disruption,partial chromatin loss,and positive expression of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue decreased(P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly increased(P<0.01).Compared with the model group,the treatment groups showed an increased number of nucleus pulposus cells with orderly arrangement and more extracellular matrix,the ultrastructural damage of the cell membrane,organelle and nucleus in nucleus pulposus cells was partially restored under transmission electron microscopy,the positive expressions of Aggrecan and Collagen Ⅱ significantly increased in Bushen Huoxue Prescription medium-and high-dosage groups and the ibuprofen group(P<0.05,P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly decreased(P<0.05,P<0.01).Conclusion Bushen Huoxue Prescription may delay intervertebral disc degeneration of the model rabbit by inhibiting the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus cells,and promoting the generation of extracellular matrix components Aggrecan and Collagen Ⅱ.

Objective To observe the effects of Bushen Huoxue Prescription on pressure-induced necroptosis in human nucleus pulposus cells and the expressions of RIPK1/RIPK3/MLKL pathway;To explore its potential mechanism in delaying intervertebral disc degeneration.Methods Human primary nucleus pulposus cells were cultured in vitro,and a model of nucleus pulposus cell degeneration was established using continuous load pressure method.After modeling,the nucleus pulposus cells were divided into model group,Bushen Huoxue Prescription group and inhibitor group,blank serum,Bushen Huoxue Prescription containing serum and necroptotic apoptosis inhibitor(Nec-1)intervention were administered,respectively.Normal group nucleus pulposus cells were cultured routinely.AO/EB fluorescence dual staining method was used for detecting cell apoptosis,flow cytometry was used to detect the necroptosis rate of nucleus pulposus cells,Western blot was used to detect the protein expressions of p-receptor interacting protein kinase(RIPK)1,p-RIPK3 and p-mixed lineage kinase domain like protein(MLKL),RT-qPCR was used to detect the mRNA expressions of RIPK1,RIPK3 and MLKL.Results Compared with the normal group,the model group showed more red fluorescence under AO/EB staining of nucleus pulposus cells,which were round and condensed,the necroptosis rate of nucleus pulposus cells increased(P<0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL increased(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expression increased(P<0.01).Compared with the model group,Bushen Huoxue Prescription group and the inhibitor group had less red condensed chromatin in the nucleus pulposus cells,Bushen Huoxue Prescription group had a lower rate of necroptosis(P<0.05),while the inhibitor group showed a decreasing trend in necroptosis rate(P>0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL decreased in Bushen Huoxue Prescription group and the inhibitor group(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expressions decreased(P<0.01).Conclusion Bushen Huoxue Prescription can alleviate pressure-induced damage to nucleus pulposus cells and inhibit necroptosis,thereby slowing the progression of intervertebral disc degeneration.Its mechanism may be related to the RIPK1/RIPK3/MLKL pathway mediated necroptosis.

Objective To investigate the protective effect of hederagenin(HDG)on cisplatin(Cis)-induced acute kidney injury(AKI)in mice and its potential mechanism.Methods 24 male C57BL/6J mice were randomly divided into a control group,AKI model group,HDG low-dose group,and HDG high-dose group,with six mice in each group.AKI model was established by intraperitoneal injection of 20 mg/kg cisplatin(Cis).The HDG low-dose and HDG high-dose groups were given 20,40 mg/kg HDG by intragastric administration,respectively,and samples were collected 3 days later.The kidneys of the mice were collected for hematoxylin-eosin(HE)and periodic-acid-schiff(PAS)staining to evaluate the kidney pathology,and serum was collected to detect changes in serum creatinine(Scr)and blood urea nitrogen(BUN).The expression of p-P65,P65,IL-6,TNF-α,IL-1β,and other inflammatory-related proteins was detected by Western Blot.A TCMK1(renal tubular epithelial cell)inflammatory cell model was established by Cis(200 ng/mL)stimulation in vitro.Blank group,Cis model group,HDG low-dose group,HDG high-dose group,Axin2 overexpression group,HDG+Axin2 overexpression group were set up.In the Axin2-overexpression group,the expression of p-P65,P65,IL-6,TNF-α,IL-1β,Axin2,and AREG was detected among total cell proteins.Results Compared with the control group,AKI model mice exhibited significantly elevated serum creatinine and blood urea nitrogen levels(P<0.05),accompanied by pathological alterations including vacuolar degeneration of renal tubules,inflammatory cell infiltration,and glycogen deposition,and the expression of inflammation-related proteins(p-P65,TNF-α,IL-6,IL-1β)and Axin2 was markedly upregulated in AKI mice(P<0.05).HDG treatment induced a dose-dependent reduction in serum creatinine and blood urea nitrogen levels(high-dose>low-dose,P<0.05),alleviated renal histopathological damage,and concurrently suppressed the expression of these inflammatory mediators and Axin2(P<0.05).HDG was confirmed that dose-dependently inhibited Cis-induced upregulation of Axin2,and inflammatory cytokines in vitro experiments.Transcriptome sequencing revealed that Axin2 overexpression significantly increased amphiregulin(AREG)expression(P<0.05).Mechanistically,HDG reduced p-P65 phosphorylation by suppressing the Axin2/AREG axis(P<0.05),while Axin2 overexpression abolished the protective effects of HDG against Cis-induced renal tubular cell injury.Conclusions HDG protects against renal injury in AKI mice by reducing inflammation through the inhibition of Axin2/AREG axis activation.

Objective To evaluate the safety and efficacy of non-retrograde intubation combined with selectively tubeless percutaneous nephrolithotomy(NR-ST-PCNL).Methods A retrospective analysis included 213 patients with upper urinary tract stones and hydronephrosis(renal pelvic separation>10 mm)undergoing PCNL at our hospital from October 2023 to June 2025.Patients were divided into Group A(non-retrograde intuba-tion,n=109)and Group B(retrograde intubation,n=104).Primary endpoint was postoperative complications and secondary endpoints included operative time,stone-free rate(SFR),visual analog scale(VAS)pain scores,postoperative hospital stay,and hospitalization costs.Results Group A demonstrated significantly lower rates of postoperative complications[7.3%(8/109)vs.18.2%(19/104),P=0.017],shorter operative time[51.00(37.00,65.00)min vs.71.50(55.00,90.75)min,P<0.001],lower postoperative VAS scores[1.00(0.00,1.00)vs.1.00(0.00,2.00),P=0.008],shorter hospital stay[3.00(2.00,3.00)days vs.4.00(4.00,4.00)days,P<0.001],and lower hospitalization costs[17 028.00(15 178.05,17 934.50)RMB vs.20 653.00(19 176.25,22 630.00)RMB,P<0.001]compared with Group B.There was no significant difference in SFR between groups(P>0.05).Conclusion For patients with upper urinary tract stones and renal pelvic separation>10 mm,NR-ST-PCNL performed by experienced surgeons achieves comparable stone clearance to conventional techniques while reducing complication risk,shortening operative and hospitalization times,and lowering costs.It represents a safe,efficient,and optimized clinical approach.

Objective To investigate the protective effect of hederagenin(HDG)on cisplatin(Cis)-induced acute kidney injury(AKI)in mice and its potential mechanism.Methods 24 male C57BL/6J mice were randomly divided into a control group,AKI model group,HDG low-dose group,and HDG high-dose group,with six mice in each group.AKI model was established by intraperitoneal injection of 20 mg/kg cisplatin(Cis).The HDG low-dose and HDG high-dose groups were given 20,40 mg/kg HDG by intragastric administration,respectively,and samples were collected 3 days later.The kidneys of the mice were collected for hematoxylin-eosin(HE)and periodic-acid-schiff(PAS)staining to evaluate the kidney pathology,and serum was collected to detect changes in serum creatinine(Scr)and blood urea nitrogen(BUN).The expression of p-P65,P65,IL-6,TNF-α,IL-1β,and other inflammatory-related proteins was detected by Western Blot.A TCMK1(renal tubular epithelial cell)inflammatory cell model was established by Cis(200 ng/mL)stimulation in vitro.Blank group,Cis model group,HDG low-dose group,HDG high-dose group,Axin2 overexpression group,HDG+Axin2 overexpression group were set up.In the Axin2-overexpression group,the expression of p-P65,P65,IL-6,TNF-α,IL-1β,Axin2,and AREG was detected among total cell proteins.Results Compared with the control group,AKI model mice exhibited significantly elevated serum creatinine and blood urea nitrogen levels(P<0.05),accompanied by pathological alterations including vacuolar degeneration of renal tubules,inflammatory cell infiltration,and glycogen deposition,and the expression of inflammation-related proteins(p-P65,TNF-α,IL-6,IL-1β)and Axin2 was markedly upregulated in AKI mice(P<0.05).HDG treatment induced a dose-dependent reduction in serum creatinine and blood urea nitrogen levels(high-dose>low-dose,P<0.05),alleviated renal histopathological damage,and concurrently suppressed the expression of these inflammatory mediators and Axin2(P<0.05).HDG was confirmed that dose-dependently inhibited Cis-induced upregulation of Axin2,and inflammatory cytokines in vitro experiments.Transcriptome sequencing revealed that Axin2 overexpression significantly increased amphiregulin(AREG)expression(P<0.05).Mechanistically,HDG reduced p-P65 phosphorylation by suppressing the Axin2/AREG axis(P<0.05),while Axin2 overexpression abolished the protective effects of HDG against Cis-induced renal tubular cell injury.Conclusions HDG protects against renal injury in AKI mice by reducing inflammation through the inhibition of Axin2/AREG axis activation.

Objective To observe the effects of Bushen Huoxue Prescription on the pathway related to necroptosis of nucleus pulposus cells in a model rabbit of intervertebral disc degeneration;To explore its mechanisms in delaying intervertebral disc degeneration.Methods A intervertebral disc degeneration rabbit model was established using the spinal instability method.Totally 40 model rabbits were randomly divided into model group,ibuprofen group and Bushen Huoxue Prescription low-,medium-and high-dosage groups.Additionally,a normal control group and a sham-operation group were set up,with 8 rabbits in each group.Each treatment groups received the corresponding drugs via gavage for two consecutive weeks.HE staining was used to observe morphology of nucleus pulposus tissue,transmission electron microscopy was used to observe ultrastructure in nucleus pulposus cells,immunohistochemical staining was used to assess the expressions of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue,Western blot was used to detect the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus tissue.Results Compared with the sham-operation group,the model group showed a significant decrease in nucleus pulposus cells,disordered cell arrangement,reduced extracellular matrix,interrupted cell membrane continuity under transmission electron microscopy,organelle swelling,nuclear membrane disruption,partial chromatin loss,and positive expression of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue decreased(P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly increased(P<0.01).Compared with the model group,the treatment groups showed an increased number of nucleus pulposus cells with orderly arrangement and more extracellular matrix,the ultrastructural damage of the cell membrane,organelle and nucleus in nucleus pulposus cells was partially restored under transmission electron microscopy,the positive expressions of Aggrecan and Collagen Ⅱ significantly increased in Bushen Huoxue Prescription medium-and high-dosage groups and the ibuprofen group(P<0.05,P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly decreased(P<0.05,P<0.01).Conclusion Bushen Huoxue Prescription may delay intervertebral disc degeneration of the model rabbit by inhibiting the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus cells,and promoting the generation of extracellular matrix components Aggrecan and Collagen Ⅱ.

Objective To observe the effects of Bushen Huoxue Prescription on pressure-induced necroptosis in human nucleus pulposus cells and the expressions of RIPK1/RIPK3/MLKL pathway;To explore its potential mechanism in delaying intervertebral disc degeneration.Methods Human primary nucleus pulposus cells were cultured in vitro,and a model of nucleus pulposus cell degeneration was established using continuous load pressure method.After modeling,the nucleus pulposus cells were divided into model group,Bushen Huoxue Prescription group and inhibitor group,blank serum,Bushen Huoxue Prescription containing serum and necroptotic apoptosis inhibitor(Nec-1)intervention were administered,respectively.Normal group nucleus pulposus cells were cultured routinely.AO/EB fluorescence dual staining method was used for detecting cell apoptosis,flow cytometry was used to detect the necroptosis rate of nucleus pulposus cells,Western blot was used to detect the protein expressions of p-receptor interacting protein kinase(RIPK)1,p-RIPK3 and p-mixed lineage kinase domain like protein(MLKL),RT-qPCR was used to detect the mRNA expressions of RIPK1,RIPK3 and MLKL.Results Compared with the normal group,the model group showed more red fluorescence under AO/EB staining of nucleus pulposus cells,which were round and condensed,the necroptosis rate of nucleus pulposus cells increased(P<0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL increased(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expression increased(P<0.01).Compared with the model group,Bushen Huoxue Prescription group and the inhibitor group had less red condensed chromatin in the nucleus pulposus cells,Bushen Huoxue Prescription group had a lower rate of necroptosis(P<0.05),while the inhibitor group showed a decreasing trend in necroptosis rate(P>0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL decreased in Bushen Huoxue Prescription group and the inhibitor group(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expressions decreased(P<0.01).Conclusion Bushen Huoxue Prescription can alleviate pressure-induced damage to nucleus pulposus cells and inhibit necroptosis,thereby slowing the progression of intervertebral disc degeneration.Its mechanism may be related to the RIPK1/RIPK3/MLKL pathway mediated necroptosis.

Objective To evaluate the safety and efficacy of non-retrograde intubation combined with selectively tubeless percutaneous nephrolithotomy(NR-ST-PCNL).Methods A retrospective analysis included 213 patients with upper urinary tract stones and hydronephrosis(renal pelvic separation>10 mm)undergoing PCNL at our hospital from October 2023 to June 2025.Patients were divided into Group A(non-retrograde intuba-tion,n=109)and Group B(retrograde intubation,n=104).Primary endpoint was postoperative complications and secondary endpoints included operative time,stone-free rate(SFR),visual analog scale(VAS)pain scores,postoperative hospital stay,and hospitalization costs.Results Group A demonstrated significantly lower rates of postoperative complications[7.3%(8/109)vs.18.2%(19/104),P=0.017],shorter operative time[51.00(37.00,65.00)min vs.71.50(55.00,90.75)min,P<0.001],lower postoperative VAS scores[1.00(0.00,1.00)vs.1.00(0.00,2.00),P=0.008],shorter hospital stay[3.00(2.00,3.00)days vs.4.00(4.00,4.00)days,P<0.001],and lower hospitalization costs[17 028.00(15 178.05,17 934.50)RMB vs.20 653.00(19 176.25,22 630.00)RMB,P<0.001]compared with Group B.There was no significant difference in SFR between groups(P>0.05).Conclusion For patients with upper urinary tract stones and renal pelvic separation>10 mm,NR-ST-PCNL performed by experienced surgeons achieves comparable stone clearance to conventional techniques while reducing complication risk,shortening operative and hospitalization times,and lowering costs.It represents a safe,efficient,and optimized clinical approach.

Objective To compare the efficacy and safety of flexible ureteral lithotripsy(FURL)and non-retrograde percutaneous nephrolithotomy(NR-PCNL)for treating1.5-2.0 cm upper ureteral stones.Methods We retrospectively analyzed clinical data of 130 patients with upper ureteral stones treated between October 2022 and October 2024.Sixty-two patients underwent FURL and 68 underwent NR-PCNL.Comparisons included operative time,pre-and postoperative changes in white blood cells(WBC),hemoglobin(Hb),and creatinine(Cr),postoperative C-reactive protein(CRP)levels,stone-free rate after primary surgery,postoperative hospitalization duration,pain scores,complications,and need for auxiliary treatments.Results Compared to the FURL group,the NR-PCNL group demonstrated advantages in operative time[54.0(44.3,69.3)min vs.82.5(66.0,101.0)min,Z=-5.565,P<0.001],WBC elevation[1.9(0.5,3.5)×109/L vs.4.5(3.0,6.0)×109/L,Z=-4.528,P<0.001],and secondary surgery rate[0%(0/68)vs.14.5%(9/62),P<0.001].The FURL group showed lower Hb reduction[3.0(2.0,6.3)g/L vs.8.0(5.0,11.0)g/L,Z=-4.262,P<0.001],less postoperative Visual Analogue Scale(VAS)pain scores[1.0(1.0,2.0)points vs.2.0(1.0,2.0)points,Z=-2.840,P=0.005],and shorter hospitalization duration[2.0(1.0,2.0)d vs.3.0(2.0,3.0)d,Z=-5.815,P<0.001].No significant differences were observed in Cr elevation,CRP levels,stone-free rate after primary surgery,complications,or analgesic requirements(P≥0.05).Conclusions Both NR-PCNL and FURL are safe and effective for 1.5-2.0 cm upper ureteral stones.FURL offers better patient comfort,while NR-PCNL shows superior overall safety.