BackgroundDiabetic kidney disease (DKD) is widely recognized as a major contributor to end-stage renal disease, in which podocyte injury serves as an important pathological basis for disease progression. ZhiXiaoSanZheng Formula (ZXSZF), an empirically derived traditional Chinese medicine prescription, has shown therapeutic potential in DKD; however, its molecular mechanisms remain unclear. This study investigated whether ZXSZF protects podocytes by modulating ferroptosis-related pathways.MethodsThe chemical profile of ZXSZF was analyzed by LC-MS/MS. Potential bioactive compounds were screened through SwissADME, and putative targets were predicted using SwissTargetPrediction. Overlapping targets among ZXSZF, DKD, and ferroptosis were identified and analyzed through protein-protein interaction and functional enrichment analyses. The predicted mechanisms were further validated in a unilateral nephrectomy plus STZ-induced DKD rat model and in AGEs-stimulated MPC5 podocytes.ResultsLC-MS/MS analysis identified 94 chemical constituents in ZXSZF. Network pharmacology analysis suggested that antioxidant and ferroptosis-related pathways centered on NRF2 may represent potential regulatory nodes of ZXSZF. In DKD rats, ZXSZF reduced albuminuria and improved renal histopathological changes, accompanied by restoration of podocyte markers and attenuation of ferroptosis-associated alterations. In AGEs-stimulated podocytes, ZXSZF decreased lipid peroxidation and iron accumulation while enhancing cellular antioxidant capacity. These effects were associated with increased NRF2 signaling and upregulation of SLC7A11 and GPX4. Pharmacological inhibition of NRF2 with ML385 partially attenuated the protective effects of ZXSZF.ConclusionsZXSZF alleviates podocyte injury in DKD and its renoprotective effects are associated with modulation of ferroptosis-related processes involving the NRF2/SLC7A11/GPX4 pathway. The present study provides experimental evidence for the mechanistic basis of ZXSZF and supports its potential role as a complementary therapeutic option in DKD management.

While Pan-Immune-Inflammation Value (PIV) has been associated with chronic kidney disease of various etiologies, there is a lack of studies specifically analyzing the relationship between PIV and diabetic kidney disease (DKD) in individuals with type 2 diabetes mellitus (T2DM). This study aimed to explore the association between PIV and DKD. The data were obtained from Guang’anmen Hospital and 38 community health service centers, spanning the period from 2014 to 2022. This study conducted a cross-sectional study including 7,610 T2DM patients and a cohort study comprising 1,494 T2DM patients without baseline kidney disease. In both studies, multivariable-adjusted logistic regression models and restricted cubic spline (RCS) analyses were used to assess the relationship between PIV and DKD. In the cross-sectional study, after adjusting for potential confounders, PIV was significantly and positively associated with DKD prevalence in T2DM patients, with those in the highest quartile exhibiting a 76.3

ETHNOPHARMACOLOGICAL RELEVANCE:Pholidota chinensis Lindl. (P. chinensis), a traditional medicinal plant, exhibits notable antioxidant, anti-inflammatory, and antidiabetic properties. In Traditional Chinese Medicine, its pseudobulbs are applied for treating cough, bronchitis, diabetes, and diabetic kidney disease (DKD). The potential mechanism through which P. chinensis alleviates DKD requires further investigation. AIM OF THE STUDY:This investigation was designed to evaluate the potential of P. chinensis to optimize mitochondrial function via the dual regulation of dynamic remodeling and mitophagic flux within DKD models. MATERIALS AND METHODS:A DKD animal model was induced through unilateral nephrectomy and streptozotocin administration. Various parameters were evaluated, such as renal function, histopathology, inflammatory and fibrotic markers, and proteins related to mitochondrial fission-fusion balance and mitophagy. In vitro, AGEs-treated HK-2 cell model was employed to assess autophagic flux and mitochondrial function via adenoviral mCherry-GFP-LC3B transduction, JC-1 assay, together with measurements of ROS and ATP production. RESULTS:P. chinensis showed clear renoprotective effects in DKD rats, mainly by alleviating renal inflammation and fibrotic changes. Treatment was associated with improved mitochondrial dynamics, characterized by increased expression of mitochondrial fusion-related proteins (Mfn1, Opa1) and reduced levels of fission-related proteins (Drp1, Fis1). Meanwhile, a pronounced activation of mitophagy was observed, evidenced by increased levels of core regulators involved in the PINK1/Parkin pathway and autophagosome formation, along with reduced p62 accumulation. In vitro, P. chinensis exerted antioxidative effects by enhancing SOD activity while reducing MDA levels. It also facilitated autophagy activation and autophagosome-lysosome fusion, leading to improved mitochondrial membrane potential, reduced ROS production, and increased ATP generation. CONCLUSION:Overall, P. chinensis improves mitochondrial quality control by promoting fusion, reactivating mitophagy, and enhancing autophagic flux, thereby facilitating mitochondrial clearance and contributing to the attenuation of kidney injury and the slowing of DKD progression.

ObjectiveOxidative stress and inflammation have been implicated in kidney stone disease. The Composite Dietary Antioxidant Index (CDAI) reflects the combined intake of multiple dietary antioxidants, but its association with kidney stones and the potential statistical contribution of immune-inflammatory markers remain unclear. This study aimed to examine the association between CDAI and kidney stones and to explore the potential statistical contribution of systemic immune-inflammatory markers to this association.MethodsThis was a retrospective cross-sectional study of adults aged ≥18 years. We analyzed data from 26,485 participants in the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Survey-weighted logistic regression was used to examine the association between CDAI and self-reported history of kidney stones. Restricted cubic spline analyses were performed to assess nonlinear associations, and subgroup, sensitivity, and exploratory mediation analyses were conducted.ResultsAfter full adjustment for potential confounders, higher CDAI was inversely associated with kidney stones (OR = 0.97, 95% CI: 0.96-0.99). When CDAI was categorized into quartiles (Q1-Q4), participants in the highest CDAI quartile had 22% lower odds of kidney stones compared with Q1 (OR = 0.78, 95% CI: 0.66, 0.93). Restricted cubic spline analysis suggested a nonlinear inverse association that tended to plateau at higher CDAI levels. Furthermore, exploratory mediation analyses suggested statistical indirect associations through the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and neutrophil-to-lymphocyte ratio (NLR), with indirect association proportions of 3.11%, 5.27%, and 3.14%, respectively. The advanced lung inflammation index (ALI) showed no significant indirect association.ConclusionsIn this nationally representative cross-sectional study, higher CDAI was inversely associated with kidney stones. Exploratory mediation analyses suggested statistical indirect associations through immune-inflammatory markers. These findings should be interpreted as hypothesis-generating and require confirmation in prospective studies.

Early identification of high-risk individuals for coronary artery disease (CAD) is critical, especially in acute coronary syndrome (ACS) patients who face elevated risks of adverse cardiovascular events and are in need of intensified secondary prevention. This study aimed to investigate the combined value of the triglyceride-glucose (TyG) index—a surrogate marker of insulin resistance—and the systemic inflammatory response index (SIRI), calculated as (neutrophil count × monocyte count)/ lyphocyte count, in assessing coronary artery stenosis severity, proposing a cost-effective strategy for risk stratification in ACS management. A retrospective cohort study included 415 ACS patients diagnosed by coronary angiography at Beijing University of Chinese Medicine Third Affiliated Hospital (June 2021–February 2024). Patients were stratified into low stenosis (Gensini score < 34, n = 204) and high stenosis (Gensini score ≥ 34, n = 211) groups based on the median Gensini score. Clinical parameters and inflammatory markers were analyzed using logistic regression and ROC curves. High stenosis group showed significantly higher TyG (1.95 vs. 1.42, P < 0.001) and SIRI (1.07 vs. 0.75, P < 0.001) than the low stenosis group. Both indices independently associated with severe stenosis (OR = 3.094 and 2.064, P < 0.001). The combined TyG-SIRI model achieved an AUC of 0.744 (sensitivity 61.61

OBJECTIVE:To assess the benefits of Qingre Xiaozheng formula (, QRXZF) as an adjunct to standard Western medical management on renal outcomes in patients with diabetic kidney disease (DKD). METHODS:This retrospective study included patients with DKD who received the QRXZF between May 2017 and May 2021. A total of 144 patients with DKD, 24 h urinary total protein (24 h-UTP) ≥ 0.5 g, and estimated glomerular filtration rate (eGFR) ≥ 30 mL/min per 1.73 m2 were divided into the treatment group or the control group based on whether they received QRXZF treatment. The long-term renal outcomes of patients with DKD were analyzed to evaluate the effectiveness of the QRXZF. Differences in overall survival (OS) were assessed using Kaplan-Meier curve analysis. Cox proportional hazards regression analysis was used to determine the independent risk factors for renal endpoints. RESULTS:The mean follow-up period was (28±15) months. Nine (12.5%) patients in the treatment group and 27 (37.5%) patients in the control group met the renal endpoints. Multivariate Cox regression analysis showed that 24 h-UTP ≥ 3.5 g [hazard ratio (HR) = 4.70, 95% confidence interval (CI) (1.83, 12.05), P = 0.001], combined coronary artery disease [HR = 3.39, 95% CI (1.65, 6.98), P = 0.001], total cholesterol [HR = 1.34, 95% CI (1.05, 1.70), P = 0.019] and low-density lipoprotein [HR = 1.65, 95% CI (1.111, 2.45), P = 0.013] were independent prognostic factors for renal endpoints in patients with DKD. Compared with the treatment group, the risk of renal endpoint events increased 2.68-fold in the control group [HR = 2.68, 95% CI (1.19, 6.02); P = 0.017]. We included 48 patients with 24 h-UTP ≥ 3.5 g in a further stratification analysis of patients with DKD. The independent risk factor for the renal endpoints in patients with 24h-UTP ≥ 3.5 g was smoking history [HR = 5.52, 95% CI (1.131, 26.92), P = 0.035]. Compared with the treatment group, the risk of renal endpoint events increased 3.01-fold in the control group [HR = 3.01, 95% CI (1.05, 8.67); P = 0.041]. CONCLUSIONS:The results show that QRXZF treatment improved renal outcomes and reduced proteinuria in patients with DKD. These results indicate that Traditional Chinese Medicine is likely to have a positive therapeutic effect on established and advanced DKD. Further well-designed clinical trials with longer follow-up periods are required.

ETHNOPHARMACOLOGICAL RELEVANCE:Diabetic kidney disease (DKD), a prevalent microvascular complication of diabetes, is a leading cause of end-stage renal disease (ESRD). Emerging evidence implicates ferroptosis in DKD pathogenesis. Qing-Re-Xiao-Zheng-(Yi-Qi) Formula (QRXZYQF), a traditional Chinese medicine with a 30-year clinical application history, exhibits multifaceted pharmacological benefits. But its potential role in DKD has yet to be fully investigated. AIM OF THE STUDY:This study investigates whether QRXZYQF alleviates podocyte injury and mitigates DKD progression by modulating ferroptosis through AMP-activated protein kinase (AMPK) pathway activation. MATERIALS AND METHODS:We induced DKD in male sprague dawley (SD) rats by performing left unilateral nephrectomy followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg). Rats received QRXZYQF (12/24 g/kg), metformin (100 mg/kg), and valsartan (8 mg/kg) for 16 weeks. Renal function, blood glucose, lipid profiles, 24-h urinary protein (24 h-UTP), oxidative stress markers glutathione (GSH) and malondialdehyde (MDA), and histopathology were assessed. In vitro, high-glucose-cultured conditionally immortalized mouse podocytes (MPC-5) cells were analyzed for cell viability assays, ferroptosis markers, mitochondrial integrity, and AMPK signaling. Additionally, we used short hairpin RNA (shRNA) to suppress AMPK expression to confirm whether QRXZYQF exerts protective effects on DKD via AMPK-mediated ferroptosis signaling. RESULTS:QRXZYQF improved body weight, glucose-lipid metabolism, and renal function in DKD rats, and alleviated kidney tissue pathology, renal fibrosis and mitochondrial damage. Furthermore, QRXZYQF upregulated the expression of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) while downregulating acyl CoA synthase long-chain family member 4 (ACSL4) expression, and attenuated oxidative stress. Moreover, AMPK silencing partially reversed QRXZYQF's protective effects, confirming AMPK-dependent ferroptosis inhibition. CONCLUSIONS:QRXZYQF attenuates DKD progression by activating AMPK signaling, thereby suppressing podocyte ferroptosis. These findings underscore its potential as a therapeutic agent for DKD.

Diabetic kidney disease (DKD) represents a leading complication of diabetes, frequently progressing to end-stage renal disease (ESRD), which significantly impairs patients’ quality of life and imposes substantial healthcare burdens. Consequently, early detection and intervention in DKD are paramount. The incorporation of surrogate endpoints in clinical trials has emerged as a pivotal strategy for assessing the efficacy of novel therapies, facilitating the reduction of trial duration and associated costs. Currently, the rate of change in estimated glomerular filtration rate (eGFR) and urinary albumin excretion, either independently or in combination, serve as reliable surrogate endpoints for evaluating DKD progression. Although novel biomarkers such as KIM-1 and TNFR2 are not yet recommended as standalone surrogate endpoints for DKD, they hold potential when used in combination with established markers, such as eGFR slope and urinary albumin change rate, to improve the prediction of ESRD risk. While omics-based indicators demonstrate promise in DKD research, their utility requires further validation, particularly through long-term follow-up and dynamic monitoring, to establish their effectiveness and clinical applicability. Future research should prioritize the validation and optimization of potential surrogate endpoints through long-term follow-up studies and large-scale cohorts.

Purpose:This study investigates the effect of Shenqi Shenkang granule (SQSKG) on chronic kidney disease (CKD), focusing on regulating the PI3K/AKT/mTOR pathway, autophagy, and mitochondrial homeostasis. Methods:The compounds and targets of SQSKG on CKD were identified by network pharmacology and validated by molecular docking. LC-MS/MS was used to verify the compounds screened by network pharmacology. In vitro experiments based on HK-2 cells were used to assess its impact on cell migration, viability, oxidative stress, and key proteins of the PI3K/AKT/mTOR pathway, autophagy, and fibrosis. Mitochondrial function and autophagic flux were evaluated via JC-1, Mito-Tracker, and Ad-mCherry-GFP-LC3B assays. In vivo, an adenine-induced CKD rat model was used to analyze renal function, fibrosis, and autophagy through serum/urine tests, histology, and immunofluorescence. Results:Network pharmacology identified 49 compounds and 149 targets associated with SQSKG's therapeutic effects on CKD, highlighting critical targets such as AKT1, MAPK1, EGFR, HSP90AA, and IGF1R. The primary mechanism involves the PI3K/AKT pathway. In vitro experiments demonstrated that SQSKG significantly enhanced cell migration, colony formation, viability in AGEs-treated HK-2 cells, and exhibited robust antioxidant properties by increasing SOD levels and reducing MDA and ROS production. SQSKG effectively inhibited the phosphorylation of PI3K, AKT, and mTOR, and reduced TGF-β fluorescence intensity in kidney tissue. Autophagic flux analysis showed that SQSKG increased autophagic activity and reduced p62 accumulation. Additionally, JC-1 and Mito-Tracker Green assays demonstrated that SQSKG improved mitochondrial membrane potential and morphology. In vivo, SQSKG significantly improved renal function and alleviated renal fibrosis in a dose-dependent manner, reversing fibrosis marker overexpression (Col-I, α-SMA, TGF-β) and activating autophagy. Conclusion:Our findings provide novel insights into the therapeutic potential of SQSKG in CKD management, highlighting its ability to modulate PI3K/AKT/mTOR pathway, activating autophagy flux, and restoring mitochondrial integrity, thereby offering a promising complementary or alternative treatment option for patients with CKD.

Mitochondrial homeostasis imbalance plays an important role in the development of diabetic kidney disease (DKD). Kaempferol is a key bioactive compound widely present in the rhizomes of Kaempferia L. and vegetables. Its anti-inflammatory and antioxidant properties have gained increasing attention in treating various metabolic diseases. This study investigated whether kaempferol could improve mitochondrial structure and function by regulating mitochondrial dynamics and mitophagy in DKD. A DKD rat model was established via unilateral nephrectomy and streptozotocin injection. Renal function, histopathology, and inflammatory factors were assessed, along with fibrosis, apoptosis, mitochondrial dynamics, and mitophagy-related proteins. Meanwhile, an AGEs-induced HK-2 cell injury model was used to evaluate autophagic flux and mitochondrial function and morphology through ad-mCherry-GFP-LC3B transduction, JC-1 staining, and MitoTracker probes. In vivo results showed that kaempferol exhibited significant anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in DKD rats. Moreover, kaempferol demonstrated good safety by alleviating hepatic fibrosis. It also restored mitochondrial dynamics by promoting the upregulation of mitochondrial fusion proteins (Mfn1, OPA1) and the downregulation of fission proteins (Drp1, Fis1). In addition, kaempferol enhanced mitochondrial biogenesis by upregulating PGC-1α and TFAM. Notably, kaempferol reactivated mitophagy, as evidenced by increased levels of PINK1, Parkin, LC3, Beclin1, and ATG5, along with a reduction in p62 levels. In vitro, kaempferol further demonstrated its antioxidative potential by increasing SOD levels and decreasing MDA levels. Additionally, it promoted autophagic induction and facilitated the fusion of autophagosomes with lysosomes. These combined effects led to the restoration of mitochondrial membrane potential and structural integrity, while reducing ROS production and enhancing ATP generation. In conclusion, kaempferol promotes mitochondrial fusion, restores mitophagy, enhances autophagy flux, and facilitates mitochondrial clearance, showing the potential to mitigate kidney injury and slow disease progression in DKD.

The relationship between muscle mass and visceral fat with mortality risk in diabetes has been extensively studied. This study investigates the association between the appendicular skeletal muscle mass-to-visceral fat area ratio (SVR) and cardiovascular and cancer-related mortality in diabetic patients in the United States. A nationwide cohort study was conducted using NHANES data (2011-2018), including 1439 diabetic patients with dual-energy X-ray absorptiometry (DXA) measurements. Weighted Cox proportional hazards models and restricted cubic splines (RCS) were employed to evaluate the association between SVR and cause-specific mortality rates. Weighted receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of SVR and other conventional indicators in predicting mortality. After adjusting for multiple confounding factors, SVR showed a linear negative association with cardiovascular and cancer-related mortality in diabetes. Each 0.01-unit increase in SVR was associated with a 3% reduction in the risk of cardiovascular death and a 2% reduction in cancer-related death. However, SVR demonstrated weak diagnostic performance for both cardiovascular and cancer mortality, with weighted AUCs of 0.520 and 0.527, respectively, compared to other metrics including BMI, WC, ASM, and VFA. Although SVR was significantly associated with cardiovascular and cancer mortality, its predictive performance was not superior to that of simpler or more established indicators, suggesting that it has limited clinical utility for predicting mortality in diabetic patients.

Previous studies have emphasized the independent effects of anthropometric indices—including body mass index (BMI), A Body Shape Index (ABSI), waist-to-height ratio (WHtR), body roundness index (BRI), and Conicity Index—on mortality. However, their combined impact, especially in diabetic populations with distinct obesity patterns, has been less frequently explored. This study investigates both the independent and combined effects of these anthropometric indices on mortality in diabetic Americans and compares their individual and combined diagnostic value. A nationally representative cohort study was conducted using NHANES data (2005–2018), including 6,572 diabetic adults. Weighted Cox proportional hazards models and restricted cubic splines were applied to evaluate the independent and combined associations of anthropometric indices (BMI, ABSI, WHtR, BRI, and Conicity Index) with all-cause mortality. The weighted receiver operating characteristic (ROC) curve was used to assess the diagnostic value of individual anthropometric indices and their combinations in predicting mortality. Among all the anthropometric indices, ABSI exhibited the strongest independent association with all-cause mortality, outperforming other measures such as BMI, WHtR, BRI, and Conicity Index. A clear linear relationship was identified, with higher ABSI tertiles consistently linked to an increased risk of mortality. Notably, within each BMI tertile, ABSI effectively differentiated mortality risk, particularly in the highest tertile. Furthermore, ABSI demonstrated the highest predictive performance among individual metrics (weighted AUC = 0.653) and showed further improvement when combined with BMI (weighted AUC = 0.669). BMI and ABSI collectively provide a comprehensive evaluation of mortality risk in diabetic populations, capturing the synergistic effects of general and central obesity. These findings highlight the importance of integrating BMI and ABSI into risk assessments to identify high-risk individuals and guide targeted interventions for reducing mortality.

BackgroundSecretory leukocyte protease inhibitor (SLPI) is a multifunctional protein involved in the chronic inflammatory process, implicated in the pathogenesis of diabetic kidney disease (DKD). However, its potential as a diagnostic and prognostic biomarker of DKD has yet to be evaluated. This study explored the clinical utility of SLPI in the diagnosis and prognosis of renal endpoint events in patients with DKD.MethodsA multi-center cross-sectional study comprised of 266 patients with DKD and a predictive cohort study comprised of 120 patients with stage IV DKD conducted between December 2016 and January 2022. The clinical parameters were collected for statistical analysis, a multivariate Cox proportional hazards model was used to evaluate the independent risk factors for renal endpoints.ResultsSerum SLPI levels gradually increased with DKD progression (p<0.01). A significant correlation was observed between serum SLPI levels and renal function in patients with DKD. The mean follow-up duration in this cohort study was 2.32 ± 1.30 years. Multivariate Cox regression analysis showed SLPI levels≥51.61ng/mL (HR=2.95, 95% CI[1.55, 5.60], p<0.01), 24h urinary protein levels≥3500 mg/24h (HR=3.02, 95% CI[1.66, 5.52], p<0.01), Alb levels<30g/l (HR=2.19, 95% CI[1.12, 4.28], p<0.05), HGB levels<13g/dl (HR=3.18, 95% CI[1.49, 6.80], p<0.01), and urea levels≥7.1 mmol/L (HR=8.27, 95% CI[1.96, 34.93], p<0.01) were the independent risk factors for renal endpoint events in DKD patients.ConclusionsSerum SLPI levels increased with DKD progression and were associated with clinical parameters of DKD. Moreover, elevated SLPI levels showed potential prognostic value for renal endpoint events in individuals with DKD. These findings validate the results of previous studies on SLPI in patients with DKD and provide new insights into the role of SLPI as a biomarker for the diagnosis and prognosis of DKD that require validation.

Visceral adiposity index (VAI) is a reliable indicator of visceral adiposity. However, no stu-dies have evaluated the association between VAI and DKD in US adults with diabetes. Theref-ore, this study aimed to explore the relationship between them and whether VAI is a good pr-edictor of DKD in US adults with diabetes. Our cross-sectional study included 2508 participan-ts with diabetes who were eligible for the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Univariate and multivariate logistic regression were used to an-alyze the association between VAI level and DKD. Three models were used to control for pot-ential confounding factors, and subgroup analysis was performed for further verification. A tot-al of 2508 diabetic patients were enrolled, of whom 945 (37.68%) were diagnosed with DKD. Overall, the VAI was 3.36 +/- 0.18 in the DKD group and 2.76 +/- 0.11 in the control group. VAI was positively correlated with DKD (OR = 1.050, 95% CI 1.049, 1.050) after fully adjusting for co-nfounding factors. Compared with participants in the lowest tertile of VAI, participants in the highest tertile of VAI had a significantly increased risk of DKD by 35.9% (OR = 1.359, 95% CI 1.355, 1.362). Through subgroup analysis, we found that VAI was positively correlated with the occurrence of DKD in all age subgroups, male(OR = 1.043, 95% CI 1.010, 1.080), participants wit-hout cardiovascular disease(OR = 1.038, 95% CI 1.011, 1.069), hypertension (OR = 1.054, 95% CI 1.021, 1.090), unmarried participants (OR = 1.153, 95% CI 1.036, 1.294), PIR < 1.30(OR = 1.049, 95% CI 1.010, 1.094), PIR >= 3 (OR = 1.085, 95% CI 1.021, 1.160), BMI >= 30 kg/m(2) (OR = 1.050, 95% CI 1.016, 1.091), former smokers (OR = 1.060, 95% CI 1.011, 1.117), never exercised (OR = 1.033, 95% CI 1.004, 1.067), non-Hispanic white population (OR = 1.055, 95% CI 1.010, 1.106) and non-Hipanic black population (OR = 1.129, 95% CI 1.033, 1.258). Our results suggest that elevated VAI levels are closely associated with the development of DKD in diabetic patients. VAI may be a simpl-e and cost-effective index to predict the occurrence of DKD. This needs to be verified in furt-her prospective investigations.

目的 探讨"肾络癥瘕"病机指导下的清热消瘕方对糖尿病肾脏病(DKD)大鼠肾损伤的保护作用及相关潜在机制.方法 将 24 只雄性SD大鼠随机分为假手术组、模型组、清热消瘕方组和缬沙坦组,每组6 只.除假手术组外,其余组大鼠以单侧肾切除联合链脲佐菌素二联法构建DKD模型.造模成功后,清热消瘕方组给予清热消瘕方颗粒剂10.2 g/(kg·d)灌胃,缬沙坦组给予缬沙坦8 mg/(kg·d)灌胃,假手术组和模型组给予等量蒸馏水灌胃,均连续灌胃16 周.比较各组大鼠一般情况、体重、肾重体重比、肾功能相关指标、血糖及血脂水平,HE、PAS、Masson染色观察各组大鼠肾脏病理形态,免疫组化染色观察各组大鼠肾脏组织中谷胱甘肽过氧化物酶 4(GPX4)、溶质载体家族7 成员11(xCT)表达情况.结果 与假手术组比较,模型组大鼠体重和肾脏组织中GPX4、xCT阳性表达面积百分比均明显降低(P均＜0.05),肾重体重比、24 h尿蛋白总量、血尿素氮、血糖、血清胆固醇和三酰甘油水平均明显升高(P均＜0.05);肾脏肾小球体积增大,肾小管上皮细胞广泛空泡变性坏死,肾小球硬化、纤维化改变明显.与模型组比较,清热消瘕方组大鼠肾脏组织中GPX4、xCT阳性表达面积百分比均明显升高(P均＜0.05),肾重体重比、24 h尿蛋白总量、血尿素氮、血清胆固醇水平均明显降低(P均＜0.05);肾小球系膜基质增生减少,纤维化程度有所缓解.结论 清热消瘕方可有效减轻DKD肾损伤和上调肾脏GPX4、xCT表达,该方可能通过调控铁死亡延缓DKD的进展.

Mitochondrial dysfunction is one of the important pathogenesis of diabetic kidney disease（DKD）.Sustained hyperglycemia may inhibit mitochondrial autophagy by inhibiting AMPK-ULK1 pathway, leading to the failure of timely clearance of damaged mitochondria, impaired mitochondrial function, and accelerating the progression of DKD.In addition, based on the theory of "internal Heat induced lump",the basic etiology of DKD was damage to Yin and loss of Qi, as well as the mixed Phlegm, Heat and depression and stasis forming lump in collateral. "Internal Heat" is the initial etiology of lump of renal collateral and could be seen throughout the course of the disease.With the different manifestations of Heat syndrome in the process of DKD,the concurrent syndrome is also different: in the early stage, the main manifestations of internal Heat are desiccated Heat, stagnation Heat as well as Yin deficiency syndrome and Qi deficiency syndrome are often seen.In the middle stage, the manifestations are mainly Heat and Dampness, often accompanied by Qi deficiency syndrome, and gradually miniature lump of kidney collateral get formed.In the late stage, there were mainly turbid Heat and Damp-Heat, the proportion of Yang deficiency syndrome increased and turbid toxicity is produced.Traditional Chinese medicine has a definite effect on delaying the progression of DKD.With clearing Heat and eliminating lump method, the proteinuri can be reduced the impaired autophagy can be recovered.It is of theoretical and scientific significance to explore whether clearing Heat and eliminating disease can activate mitochondrial autophagy, remove damaged mitochondria, improve mitochondrial function, reduce glomerular sclerosis and delay the development of DKD through AMPK-ULK1 pathway, a key sensor of regulating energy metabolism.

王耀献提出辨机论治的中医诊疗模式,强调在治疗疾病时要从病机入手,并认为与慢性泌尿系统感染性疾病相关的病机主要有8种,包括初始病机、体质病机、衍生病机、对证病机、时空病机、对症病机、兼夹病机、局部病机.在治疗方面,王耀献主要针对初始病机和衍生病机以清热利湿、益气养阴、补肾疏肝为主要治法,并兼顾其他病机以行气化湿、活血利水、通淋止痛.若本病由量变发生质变进入湿、热、瘀、虚胶结不解的"微型癥瘕"阶段,则以消癥散结为主线,同时扶助正气.

辨机论治是王耀献教授为补充辨证论治之不足、更好地揭示疾病之本质而提出的临床诊疗模式.王教授认为,与高血压肾病密切相关的病机类型主要有初始病机、体质病机、对证病机、对症病机、衍生病机、共通病机、兼夹病机.临证通过辨别上述七种病机,可厘清高血压肾病的本质,从而提出针对性治疗措施.附验案两则,具体展示辨机论治在高血压肾病中的应用.

目的:探讨平均血小板体积(mean platelet volume,MPV)、血小板分布宽度(platelet distribution width,PDW)与2型糖尿病血瘀证的相关性.方法:收集553例2型糖尿病患者的临床资料,分析比较血瘀证与非血瘀证患者的肾功能指标与MPV、PDW水平.结果:(1)血瘀证患者与非血瘀证患者相比,尿素氮、血肌酐、尿酸均升高,eGFR下降;(2)血瘀证患者与非血瘀证患者相比,MPV、PDW均升高;(3)MPV与血肌酐、尿素氮、尿酸呈正相关,与eGFR呈负相关;PDW与血肌酐、尿酸呈正相关;(4)血瘀证与MPV、PDW呈正相关,随着血瘀程度的加重,MPV、PDW水平升高的回归系数逐渐增加.结论:2型糖尿病血瘀证患者与非血瘀证患者相比,肾功能更差,MPV、PDW更高;MPV、PDW与早期肾功能损伤密切相关,提示其可能成为辅助预测2型糖尿病早期肾功能损伤的新型标志物;血瘀证是MPV、PDW水平升高的危险因素之一,为临床从瘀论治2型糖尿病提供依据.