Objective To systematically review the studies on predictive models for delayed graft function (DGF) after kidney transplantation. Methods Databases including China Biology Medicine Database, China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Web of Science and CINAHL were searched to collect studies on predictive models for DGF after kidney transplantation published from the establishment of each database to June 29, 2025. Two researchers screened the literatures according to the inclusion and exclusion criteria, evaluated the quality of the literatures using the prediction model risk of bias assessment tool (PROBAST), and conducted a meta-analysis of the common predictors of the models using R software. Results A total of 12 literatures were included, involving 14 predictive models with sample sizes ranging from 103 to 24 653 cases. Donor serum creatinine level, cold ischemia time, donor age and donor body mass index were the top four common predictors. All the predictive models were at high risk of bias and low in applicability. The results of meta-analysis showed that abnormal donor body mass index, advanced donor age, prolonged cold ischemia time and elevated donor serum creatinine level were all associated with an increased risk of DGF after transplantation (all P<0.01), but there was high heterogeneity among the studies. Fixed-effect model and random-effect model were used to re-pool the effect sizes separately. The results indicated that the fixed-effect model and random-effect model had good consistency in terms of donor body mass index, donor age and cold ischemia time, while there was a significant difference in the effect sizes of the two models for donor serum creatinine level. Conclusions The predictive models for DGF risk after kidney transplantation have good predictive performance, but the overall risk of bias is high. In the future, large-sample, multicenter and high-quality prospective clinical studies should be carried out to optimize the predictive models, so as to improve their predictive ability and clinical application value.

Objective:To investigate the prevalence and influencing factors of frailty among older adults diagnosed with non-ST-segment elevation acute coronary syndrome(NSTE-ACS).Methods:We conducted a cross-sectional study involving patients aged 65 years and older with NSTE-ACS, who were admitted to the Cardiology Center and the Department of Geriatrics at Beijing Friendship Hospital, Capital Medical University, between January 2020 and November 2021.Patients were categorized into non-frail, pre-frail, and frail groups based on the FRAIL scale.We collected clinical data, including general health conditions, comorbidities, laboratory results, treatments, and comprehensive geriatric assessments.Logistic regression analysis was employed to identify the influencing factors associated with frailty and pre-frailty in older adults with NSTE-ACS.Results:A total of 528 patients with NSTE-ACS were included in the study, comprising 308 males(58.3%)and 220 females(41.7%). The age range of participants was from 65 to 90 years, with a median age of 72(68, 76)years.The prevalence of frailty among older adults with NSTE-ACS was 11.4%(60/528), while pre-frailty was observed in 51.9%(274/528), and non-frailty in 36.7%(194/528). Compared to the non-frail and pre-frail groups, patients in the frail group were older, had a higher proportion of females, exhibited a greater prevalence of chronic diseases, and presented with elevated inflammatory markers.Additionally, frail patients demonstrated poorer nutritional status and reduced functional ability(all P<0.005). Risk factors for frailty in older adults with NSTE-ACS included older age( OR=1.110, 95% CI: 1.032-1.194, P=0.005), diabetes( OR=2.489, 95% CI: 1.091-5.679, P=0.030), cerebrovascular disease ( OR=4.151, 95% CI: 1.660-10.384, P=0.002), chronic kidney disease ( OR=42.874, 95% CI: 3.957-464.513, P=0.002), and elevated white blood cell levels( OR=1.424, 95% CI: 1.125-1.802, P=0.003). Conversely, being male( OR=0.252, 95% CI: 0.105-0.604, P=0.002)was identified as a protective factor against frailty in this patient population.For pre-frail older adults with NSTE-ACS, identified risk factors included diabetes( OR=1.882, 95% CI: 1.199-2.955, P=0.006), cerebrovascular disease( OR=1.938, 95% CI: 1.176-3.195, P=0.009), and chronic kidney disease ( OR=12.137, 95% CI: 1.536-95.934, P=0.018). Similarly, being male( OR=0.601, 95% CI: 0.376-0.961, P=0.033)was also a protective factor for pre-frailty in older adults with NSTE-ACS. Conclusions:The prevalence of frailty and pre-frailty among older adults with NSTE-ACS is notably high.Common risk factors for frailty and pre-frailty in this population include female gender, diabetes, cerebrovascular disease, and chronic kidney disease.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective To investigate the genetic differences among different populations based on 13 autosomal STR loci in CODIS core.Methods Data of 13 autosomal STR loci(CSF1PO,FGA,THO1,TPOX,vWA,D3S1358,D5S818,D7S820,D8S1179,D13S317,D16S539,D18S51,D21S11)were collected from 95 populations in scientific journals between 1999 and 2021,soursed from the PubMed database,which had been published.Allele frequencies of loci were sorted out and forensic genetic parameters including gene differentiation coefficient(Gst),total heterozygosity(Ht),subpopula-tion heterozygosity(Hs)values,and Nei's DA genetic distance were calculated.Principal component analysis,phylogenetic tree,and multidimensional scale analysis were conducted to assess population ge-netic structure.Results A total of 265 alleles were detected at the 13 STR loci in these 95 popula-tions.The mean values of Gst,Ht,and Hs were 0.023 247,0.797 915 and 0.779 365.Population genetic analyses reflected significant differences among populations from Asia,Africa and Europe.In Asian populations,there was a certain degree of distinction between mainland and island populations;the Han population showed a certain degree of distinction with surrounding populations in mainland;while within the Han population,there were two distinct clusters formed by the northern Han and the south-ern Han.Conclusion The 13 autosomal STR loci in CODIS core demonstrate potential value for popu-lation identification across different groups,and may be used for the differentiation of ethnic groups,among different continental populations.

OBJECTIVES: To investigate the role of ferroptosis in diquat-induced acute kidney injury (AKI) and its molecular mechanisms. METHODS: Transgenic zebrafish models with Tg (Eco.Tshb:EGFP) labeling of the renal tubules and Tg (lyz:dsRed2) labeling of the neutrophils were both divided into control group, gentamicin (positive control) group, diquat poisoning group, ferroptosis inhibitor group. The indicators of kidney injury, inflammatory response, and ferroptosis were examined in the zebrafish, and the changes in expressions of voltage-dependent anion-selective channel protein 1 (VDAC1) and mitochondrial ferritin (FTMT) were detected using Western blotting. RESULTS: AKI induced by diquat exhibited a significant dose-effect relationship, and the severity of injury was proportional to the exposure concentration. Diquat also caused marked oxidative stress and inflammatory responses in the zebrafish models. Rhodamine metabolism assay and HE staining revealed significantly declined glomerular filtration function of the zebrafish as diquat exposure concentration increased. Immunofluorescence staining highlighted significant changes in the expressions of ferroptosis markers GPX4 and FTH1 in zebrafish renal tissues following diquat exposure. In diquat-exposed zebrafish, treatment with ferrostatin-1, a ferroptosis inhibitor, obviously upregulated GPX4 and downregulated FTH1 expressions and improved the metabolic rate of glucan labeled with rhodamine B. Diquat exposure significantly upregulated the expression of VDAC1 and FTMT in zebrafish, and the application of ferrostatin-1 and VBIT-12 (a VDAC1 inhibitor) both caused pronounced downregulation of FTMT expression. CONCLUSIONS Ferroptosis is a critical mechanism underlying diquat-induced AKI, in which VDAC1 and FTMT play important regulatory roles, suggesting their potential as therapeutic target for AKI caused by diquat.
Animals ; Zebrafish ; Ferroptosis/drug effects* ; Acute Kidney Injury/chemically induced* ; Diquat/toxicity* ; Animals, Genetically Modified ; Voltage-Dependent Anion Channel 1/metabolism* ; Ferritins/metabolism* ; Oxidative Stress

Objective To investigate the effect of health failure mode and effect analysis(HFMEA)in optimizing the management process of postoperative diabetes insipidus in children undergoing neurosurgery.Methods Based on HFMEA,a management flowchart for postoperative diabetes insipidus in children undergoing neurosurgery was created.Brainstorming was adopted to identify failure modes in the workflow,analyze risk factors,and develop improvement measures,thereby refining the management flowchart.The amelioration and prognosis of diabetes insipidus in these children before(October 2022 to November 2023)and after(January 2024 to February 2025)implementation of the management flowchart were compared.Results The HFMEA-based management process for postoperative diabetes insipidus in children undergoing neurosurgery alleviated the symptoms of diabetes insipidus regarding the number of diabetes insipidus in the pediatric intensive care unit(P=0.006),the average daily urine output in the pediatric intensive care unit(P=0.001),the proportion of electrolyte abnormalities at discharge/transfer(P=0.037),the duration of mechanical ventilation(P=0.007),and the length of stay in the intensive care unit(P=0.001).Conclusion The HFMEA-based management process for postoperative diabetes insipidus in children undergoing neurosurgery is beneficial to the optimization of the management process,the alleviation of postoperative diabetes insipidus,and the improvement of prognosis in these children.
Humans ; Diabetes Insipidus/etiology* ; Neurosurgical Procedures/adverse effects* ; Child ; Postoperative Complications/therapy* ; Healthcare Failure Mode and Effect Analysis ; Intensive Care Units, Pediatric ; Risk Factors

ObjectiveTo investigate the immunomodulatory effect of polysaccharides from Astragali Radix-Angelicae Sinensis Radix herb pair（Qi-gui polysaccharides） on lipopolysaccharide（LPS）-induced RAW264.7 macrophages and to characterize the structure of the active component Qi-gui homogeneous polysaccharide（AAPS-4a）， and evaluate its protective effect on ulcerative colitis（UC）. MethodsThe effects of six Qi-gui polysaccharides（0.01-100 mg·L^-1） on the proliferation of RAW264.7 cells were assessed by cell proliferation and activity assay（CCK-8）， and enzyme-linked immunosorbent assay（ELISA） was used to investigate the effects of the six polysaccharides（3， 10 mg·L^-1） on the secretion levels of tumor necrosis factor（TNF）-α， interferon（IFN）-β， and nitric oxide（NO） in LPS-induced RAW264.7 cells. After screening for active polysaccharides， high-performance size-exclusion chromatography（HPSEC） was used to determine its homogeneity and relative molecular weight， then its characteristic functional groups were identified by Fourier transform infrared spectroscopy（FT-IR）， monosaccharide composition was analyzed by high performance liquid chromatography（HPLC）， methylation analysis combined with gas chromatography-mass spectrometry（GC-MS） was performed to determine the types and linkage modes of sugar residues， and one- and two-dimensional nuclear magnetic resonance（NMR） were used to identify the sugar residue composition and configuration of the active polysaccharide. Finally， experimental animals were divided into the normal group， model group， AAPS-4a low-dose group（50 mg·kg^-1）， AAPS-4a high-dose group（100 mg·kg^-1）， and sulfasalazine（SASP） group （75 mg·kg^-1）. Except for the normal group， the acute UC mouse model was induced using 3.5% dextran sulfate sodium salt（DSS）. Each treatment group was administered the corresponding dose via oral gavage for 7 days， and changes in body weight were recorded. After treatment， the spleen index and disease activity index（DAI） score were calculated， TNF-α and interleukin-6（IL-6） levels in the serum were detected by ELISA， and histopathological changes in colon tissue were observed by hematoxylin-eosin（HE） staining. ResultsAt the cellular level， AAPS-4a exhibited a dose-dependent inhibition of LPS-induced increases in TNF-α， IFN-β， and NO levels（P<0.01）. Structural characterization of AAPS-4a revealed that it was a homogeneous polysaccharide with a relative molecular weight of 7.6×10³ Da， consisting of mannose（Man）， glucose（Glc）， and galactose（Gal） in a molar ratio of 1.3∶23.9∶1.0. It was primarily composed of five sugar residues of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp， and 1，2-α-D-Galp. In vivo experiments showed that compared with the normal group， the model group demonstrated markedly increased DAI score and spleen index， significantly reduced colon length， and significantly elevated levels of TNF-α and IL-6（P<0.01）. Compared with the model group， the AAPS-4a high-dose group significantly reduced the DAI score and spleen index， as well as TNF-α and IL-6 levels， and improved colonic atrophy（P<0.05， P<0.01）. Pathological observations showed that AAPS-4a significantly inhibited inflammatory cell infiltration in colon tissue and alleviated pathological damage. ConclusionAAPS-4a， a neutral homogeneous polysaccharide composed of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp and 1，2-α-D-Galp， is identified as a key bioactive component contributing to the anti-UC effect of the Qi-gui herb pair. Its immunoregulatory and anti-UC properties suggest its potential as a therapeutic agent for UC.

Objective To investigate the expression of serum tumor-associated antigens(TAAs)in patients with rheumatoid arthritis(RA)and analyze their clinical significance for RA.Methods A total of 214 RA patients were enrolled in the RA group,while 198 age-and gender-matched healthy individuals were included in the HC group.Rheumatoid factor(RF),anti-cyclic citrullinated peptide antibody(Anti-CCP),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),interleu-kin-6(IL-6),ferritin levels,as well as gender,age,disease duration,disease activity score(DAS28)and clinical manifestations were collected from the RA group.The expression of TAAs in RA patients and the clinical characteristics of TAA-positive patients were analyzed.Spearman correla-tion analysis was used to evaluate the relationships between TAAs and clinical indicators in RA pa-tients.Results The positive rate of carbohydrate antigen 125(CA125)in the RA group was 8.88％,which was significantly higher than 1.01％ in the HC group(P＜0.001).Serum CA125 and cytok-eratin fragment 19(CYFRA21-1)levels in the RA group were significantly higher than those in the HC group,whereas alpha-fetoprotein(AFP),carcinoembryonic antigen(CEA),carbohydrate anti-gen 199(CA199)and neuron-specific enolase(NSE)levels were significantly lower(P＜0.001).TAA-positive patients had significantly older age and higher rates of pulmonary interstitial lesions compared to TAA-negative patients(P＜0.05).Patients with DAS28 scores＞5.1 had significantly higher CA125 levels than those with DAS28 scores ≤5.1(P＜0.05).CA125 levelswere positively corre-lated with DAS28 scores,ESR,RF,and anti-CCP antibodies(r=0.142,0.140,0.268,0.183;P＜0.05).Conclusion In RA patients,the positivity rate and levels of some serum TAAs are ele-vated,and TAA-positive patients tend to be older and have higher incidence of pulmonary interstitial lesions.CA125 levels are positively correlated with RA disease activity.

This study investigated the effects and action mechanism of tannins from Galla chinensis cream(TGCC) on the skin wound of rat tail. Male Sprague Dawley(SD) rats were randomly divided into a control group, model group, model+low-dose TGCC(50 mg per rat) group, model+high-dose TGCC group(100 mg per rat), and model+TGC+FAK inhibitor(Y15) cream(100 mg+10 mg per rat) group, with 10 rats in each group. After the rat tail skin injury model was successfully constructed, in the treatment group, corresponding drugs were applied to the wound surface, while in the control and model groups, the same amount of cream base as the TGCC group was applied by the same method. Then, sterile gauze was wrapped around the wound edge, and these operations were performed three times a day for 28 consecutive days. The wound healing status at the third, seventh, eleventh, fourteenth, twenty-first, and twenty-eighth days was recorded, and the wound healing rate and healing time were calculated. On the day after the last dose of medication, rat serum and tail skin wound tissue were collected for analyzing the activities of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), creatinine(CREA), urea, reactive oxygen species(ROS), interferon gamma(IFN-γ), interleukin(IL)-1β, IL-6, IL-4, IL-10, tumor necrosis factor(TNF)-α, as well as catalase(CAT), glutathione(GSH), lactate dehydrogenase(LDH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC), platelet endothelial cell adhesion molecule-1(CD31), and leukocyte differentiation antigen 34(CD34) in the wound tissue of rat tail skin. Hematoxylin-eosin, Masson, and sirius red staining were used to observe the morphological changes in the wound tissue of rat tail skin. The thickness of the epidermis, the number of fibroblasts and blood vessels, and the contents of collagen fibers, typeⅠ collagen(COLⅠ), and COLⅢ were calculated. The mRNA expressions of keratin 10(KRT10), KRT14, vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), epidermal growth factor(EGF), CD31, CD34, matrix metallopeptidase-2(MMP-2), MMP-9, COLⅠ, COLⅢ, desmin, fibroblast specific protein 1(FSP1), IFN-γ, IL-1β, TNF-α, IL-4, IL-6, and IL-10 in skin wound tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expressions of KRT10, KRT14, VEGF, FGF, EGF, MMP-2, MMP-9, COLⅠ, COLⅢ, desmin, FSP1, focal adhesion kinase(FAK), phosphorylated focal adhesion kinase(p-FAK), phosphatidylin-ositol-3-kinase(PI3K), phosphorylated phosphatidylin-ositol-3-kinase(p-PI3K), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results manifest that TGCC can dramatically elevate the healing rate of rat tail wounds and shorten wound healing time. Besides, it can reduce serum ROS levels, the contents of MDA, MPO, and LDH in the rat skin wound tissue, as well as the serum IFN-γ, IL-1β, IL-6, and TNF-α levels and the mRNA expression levels of IFN-γ, IL-1β, IL-6, and TNF-α in the skin wound tissue. It can elevate the activities of CAT, GSH, SOD, and T-AOC in wound tissue, the IL-4 and IL-10 contents in serum, and the mRNA expressions of IL-4 and IL-10 in the wound tissue. In addition, TGGC can inhibit inflammatory cell infiltration and increase the epidermal thickness, counts of fibroblasts and blood vessels, and contents of collagen fibers, COLⅠ, and COLⅢ. Besides, TGCC can elevate the mRNA and protein expressions of epidermal differentiation markers(KRT10 and KRT14), endothelial cell markers(CD31 and CD34), angiogenesis and fibroblast proliferation, differentiation markers(VEGF, FGF, EGF, COLⅠ, COLⅢ, desmin, and FSP1), reduce the mRNA and protein expressions of gelatinases(MMP-2 and MMP-9), and increase protein expressions of p-FAK, p-PI3K, p-Akt, p-mTOR, as well as ratios of p-FAK/FAK, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. These results suggest that TGCC can significantly facilitate skin wound healing, and its mechanism may be related to the activation of the FAK/PI3K/Akt/mTOR signaling pathway, inhibition of inflammatory cell infiltration in skin wound tissue, elevation of epidermal thickness, counts of fibroblasts and vessels, and contents of collagen fiber, COLⅠ, and COLⅢ, and reduction of MMP-2 and MMP-9 expressions, thus accelerating wound healing.
Animals ; Male ; Wound Healing/drug effects* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Skin/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Tannins/pharmacology* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Focal Adhesion Kinase 1/genetics*

This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*