Objective:To explore the effect of Hejie Jusan Decoction on pyroptosis in diabetic nephropathies (DN) rats; To explore its mechanism based on the NF-κB/nucleotide binding oligomeric domain like receptor protein 3 (NLRP3)/Caspase-1 signal pathway.Methods:Totally 60 SD rats were divided into blank group, model group, potassium losartan group, and Hejie Jusan Decoction high-, medium-, and low-dosage groups. In addition to the blank group, the other five groups were established DN rat models. Hejie Jusan Decoction high-, medium-, and low-dosage groups were given 0.5, 1.0, and 2.0 g/ml concentrations of Hejie Jusan Decoction, respectively; the potassium losartan group was orally administered with 20 mg/kg potassium losartan; The blank group and model group were given equal volumes of physiological saline by gavage, once a day, for consecutive 28 days. After medication, the levels of serum creatinine (SCr), urea nitrogen (BUN), and 24-hour urine protein (24 hUP) were detected; pathological changes in renal tissue were detected by HE staining; Western blot method was used to detect the expressions of P65, NLRP3, Caspase-1, and GSDMD protein in renal tissues.Results:Compared with the model group, the SCr, BUN, and 24-hUP of rats in the Hejie Jusan Decoction high-dosage group and the potassium losartan group decreased ( P<0.01). The expressions of P65, NLRP3, Caspase-1, and GSDMD protein in renal tissues of Hejie Jusan Decoction groups and potassium losartan group decreased ( P<0.05 or P<0.01). Conclusion:Hejie Jusan Decotion may affect pyroptosis by inhibiting the activation of NF-κB/NLRP3/Caspase-1 pathway, reducing renal function damage and pathological changes, so as to achieve the effect of treating diabetes nephropathy.

Objective To analyze the factors influencing the early recovery of renal function in patients with sepsis-associated acute kidney injury(SA-AKI).Methods A retrospective analysis was conducted on 86 SA-AKI patients treated in the Intensive Care Unit at Zhongshan Hospital,Fudan University from January 2021 to December 2022,who met both the Sepsis 3.0 diagnostic criteria and the AKI diagnostic standards.Patients were divided into a recovery group and a non-recovery group based on whether their renal function recovered within 7 days after AKI onset.Clinical data and laboratory tests of patients were compared between the two groups.Univariate and multivariate logistic analyses were used to identify risk factors affecting renal function recovery in SA-AKI patients,and ROC curve was utilized to evaluate the predictive value of these factors for early renal function recovery in SA-AKI patients.Results The renal function of 37(43.02％)patients recoveried.Compared with the recovery group,the renal replacement therapy rate,in-hospital mortality and 28-day mortality of patients in the non-recovery group were higher(P＜0.001).The multivariate logistic analysis showed that age,APACHE Ⅱ score,urine output,urine neutrophil gelatinase-associated lipocalin(NGAL),and norepinephrine dose were independent related factors affecting renal function recovery in SA-AKI patients(P＜0.05).The final model logit(P)=-4.091+0.001×urine NGAL-0.001 Xurine volume+0.040 ×age+0.073 × APACHE Ⅱ score+1.906 × norepinephrine dose.The AUC of model predicting early SA-AKI recovery was 0.823,with 73.5％of sensitivity,and 81.1％of specificity.Conclusions In SA-AKI patients,age,APACHE Ⅱ score,urine output,urine NGAL,and the dose of norepinephrine independently affect early renal function recovery,and the combined assessment of these indicators has predictive value for the early renal recovery in these patients.

Objective To explore the efficacy of a new anti-heart failure drug,Entresto,in the prevention of cardiotoxicity caused by doxorubicin(DOX).Methods Male adult ICR mice were randomly divided into three groups(n = 8):control group,DOX group and DOX plus Entresto group.Cardiac function of mice was measured by echocardiography.H9c2 cells were pretreated with Entresto(0-48 μmol/L)for 24 hours in the presence or absence of DOX(1 mmol/L),and then cell viability,oxidative stress,apoptosis and mitochondrial function were evaluated.Results As compared with the control group,leakage of CK,CK-MB and LDH increased significantly in the DOX group(P<0.01),and left ventricular systolic dysfunction occurred.Entresto administration reversed these changes in the DOX group.The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group(P<0.05).As compared with the DOX group,the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group(P<0.05),and mitochondrial membrane potential increased significantly(P<0.05).Entresto reversed the inhibitory effect of DOX on SIRT1/PGC-1α/MFN2 signaling pathway.Conclusions Entresto improves DOX-induced cardiotoxicity by inhibiting ROS-mediated oxidative stress and apoptosis,and its mechanism may be related to SIRT1/PGC-1α/MFN2 signal transduction pathway.