One Case of Diabetes Nephropathy Stage V, Combined Valvular Disease, Total Heart Failure with Diabetes Foot Gangrene

The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was found that the color of the thumb, index and middle toe of the left foot became black. He went to a third-class hospital in Beijing and was diagnosed as “diabetes foot”. He was treated with “balloon dilation of lower limb blood vessels of diabetes foot”. Half a year ago, the third toe on the right side was broken and treated in the hospital again. “Popliteal artery stent implantation” was given for the diagnosis of “double kidney insufficiency, diabetes foot, left heart failure, combined heart valve disease”, “Hemofiltration therapy” and anti-inflammatory, amino acid supplementation, kidney function protection, anticoagulation, anemia correction and other treatments. Later, he went to our hospital and was diagnosed by the TCM diagnosis: category of consumptive disease, toe or finger gangrene (syndrome/pattern of qi and yin deficiency). Western medicine diagnosed: stage V of diabetes nephropathy, type II diabetes foot gangrene, combined with heart valve disease, hypoalbuminemia, double kidney cyst, moderate anemia, pleural effusion, hyperkalemia, pulmonary infection, and total heart failure. The patient was treated by the Qi-acupuncture therapy of TCM in combination with Chinese and Western medicine Medical treatment made the patient significantly better and discharged.

Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2 diabetes mellitus

BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.

Tiliroside protects against diabetic nephropathy in streptozotocininduced diabetes rats by attenuating oxidative stress and inflammation

BACKGROUND Diabetic nephropathy(DN),affecting half of diabetic patients and contributing significantly to end-stage kidney disease,poses a substantial medical challenge requiring dialysis or transplantation.The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria.AIM To investigate Tiliroside's(Til)protective effect against diabetic nephropathy(DN)in rats under diabetic conditions.METHODS Five groups of six rats each were included in this study:Rats treated with DMSO by intraperitoneal injection as controls,those treated with STZ by intraperitoneal injection,those treated with STZ+Til(25 mg/kg body weight[bwt])or Til(50 mg/kg bwt),and those treated with anti-diabetic medication glibenclamide(600μg/kg bwt).Biochemical markers,fasting blood glucose,food intake,kidney weight,antioxidant enzymes,inflammatory and fibrotic markers,and renal injury were monitored in different groups.Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers.RESULTS Til significantly reduced biochemical markers,fasting blood glucose,food intake,and kidney weight and elevated antioxidant enzymes in diabetic rats.It also mitigated inflammatory and fibrotic markers,lessened renal injury,and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis.CONCLUSION These findings suggest Til's potential as a therapeutic agent for DN treatment,highlighting its promise for future drug development.

Role of cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway in diabetes and its complications

Diabetes mellitus(DM)is one of the major causes of mortality worldwide,with inflammation being an important factor in its onset and development.This review summarizes the specific mechanisms of the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway in mediating inflammatory responses.Furthermore,it compre-hensively presents related research progress and the subsequent involvement of this pathway in the pathogenesis of early-stage DM,diabetic gastroenteropathy,diabetic cardiomyopathy,non-alcoholic fatty liver disease,and other complic-ations.Additionally,the role of cGAS-STING in autonomic dysfunction and intes-tinal dysregulation,which can lead to digestive complications,has been discuss-ed.Altogether,this study provides a comprehensive analysis of the research advances regarding the cGAS-STING pathway-targeted therapeutic agents and the prospects for their application in the precision treatment of DM.

Alleviating effects and mechanisms of action of large-leaf yellow tea drinking on diabetes and diabetic nephropathy in mice

Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions(1/100 and 1/50, m/V)as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis(lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism(higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis(lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans.

The role of innate immunity in diabetic nephropathy and their therapeutic consequences

Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.

Risk evaluation for diabetic retinopathy in Chinese renalbiopsied type 2 diabetes mellitus patients

AIM:To investigate diabetic retinopathy(DR)prevalence in Chinese renal-biopsied type 2 diabetes mellitus(T2DM)patients with kidney dysfunction,and to further evaluate its relationship with diabetic nephropathy(DN)incidence and the risk factors for DR development in this population.METHODS:A total of 84 renal-biopsied T2DM patients were included.Fundus and imaging examinations were employed for DR diagnosis.Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups.Risk factors on DR development were analyzed with multiple logistic regression.RESULTS:DR prevalence was 50%in total.The incidences of DN,non-diabetic renal disease(NDRD)and mixed-type pathology were 47.6%,19.0%and 33.3%in the DR group respectively,while 11.9%,83.3%and 4.8%in the non-DR group.Systolic blood pressure,ratio of urinary albumin to creatine ratio,urinary albumin,24-hours urinary protein,the incidence and severity of DN histopathology were found statistically increased in the DR group.Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development[odds ratio(OR)=21.664,95%confidential interval(CI)5.588 to 83.991,P<0.001 for DN,and OR=45.475,95%CI 6.949 to 297.611,P<0.001 for mixed-type,respectively,in reference to (NDRD)],wherein DN severity positively correlated.CONCLUSION:Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.

Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy

AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were collected.The patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum creatinine.Optical coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)integrity.Central macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were recorded.RESULTS:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during treatment.At 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,respectively.CONCLUSION:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.

Corilagin alleviates podocyte injury in diabetic nephropathy by regulating autophagy via the SIRT1-AMPK pathway

BACKGROUND Diabetic nephropathy(DN)is the most frequent chronic microvascular consequence of diabetes,and podocyte injury and malfunction are closely related to the development of DN.Studies have shown that corilagin(Cor)has hepatoprotective,anti-inflammatory,antibacterial,antioxidant,anti-hypertensive,antidiabetic,and anti-tumor activities.AIM To explore the protective effect of Cor against podocyte injury in DN mice and the underlying mechanisms.METHODS Streptozotocin and a high-fat diet were combined to generate DN mice models,which were then divided into either a Cor group or a DN group(n=8 in each group).Mice in the Cor group were intraperitoneally injected with Cor(30 mg/kg/d)for 12 wk,and mice in the DN group were treated with saline.Biochemical analysis was used to measure the blood lipid profiles.Hematoxylin and eosin staining was used to detect pathological changes in kidney tissue.Immunohistochemistry and Western blotting were used to assess the protein expression of nephrin and podocin.Mouse podocyte cells(MPC5)were cultured and treated with glucose(5 mmol/L),Cor(50μM),high glucose(HG)(30 mmol/L),and HG(30 mmol/L)plus Cor(50μM).Real-time quantitative PCR and Western blotting RESULTS Compared with the control group,the DN mice models had increased fasting blood glucose,glycosylated hemoglobin,triglycerides,and total cholesterol,decreased nephrin and podocin expression,increased apoptosis rate,elevated inflammatory cytokines,and enhanced oxidative stress.All of the conditions mentioned above were alleviated after intervention with Cor.In addition,Cor therapy improved SIRT1 and AMPK expression(P<0.001),inhibited reactive oxygen species and oxidative stress,and elevated autophagy in HG-induced podocytes(P<0.01).CONCLUSION Cor alleviates podocyte injury by regulating autophagy via the SIRT1-AMPK pathway,thereby exerting its protective impact on renal function in DN mice.

Relationship Between Postprandial Blood Glucose,Fasting Insulin,and Glycated Hemoglobin Levels and Early Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

Objective:To investigate the relationship between postprandial blood glucose(PBG),fasting insulin(FINS),and glycated hemoglobin(HbA1c)levels and early diabetic nephropathy in patients with type 2 diabetes.Methods:96 cases of type 2 diabetes mellitus treated in our hospital from May 2021 to May 2022 were selected as the research subjects.The patients were divided into two groups according to the urinary albumin excretion rate(UAER),with 53 cases in the type 2 diabetes group(UAER<30μg/min)and 43 cases in the early diabetic nephropathy group(30μg/min≤UAER<300μg/min).PBG,FINS,and HbA1c levels were detected in 87 healthy patients.Results:The levels of PBG,FINS,and HbA1c in the early diabetic nephropathy group were higher than those in the control group(P<0.01)and the type 2 diabetes group(P<0.01).Conclusion:PBG,FINS,and HbA1c are factors affecting the occurrence of diabetic nephropathy in patients with type 2 diabetes;thus,controlling the levels of PBG,FINS,and HbA1c can effectively prevent the occurrence of diabetic nephropathy in type 2 diabetes mellitus.

Evaluating new biomarkers for diabetic nephropathy:Role ofα2-macroglobulin,podocalyxin,α-L-fucosidase,retinol-binding protein-4,and cystatin C

BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the roles and diagnostic values ofα2-macroglobulin(α2-MG),podocalyxin(PCX),α-L-fucosidase(AFU),retinol-binding protein-4(RBP-4),and cystatin C(CysC)in DN.METHODS From December 2018 to December 2020,203 T2DM patients were enrolled in the study.Of these,115 were diagnosed with DN(115 patients),while the remaining 88 patients were classified as non-DN.The urinary levels ofα2-MG,PCX,and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility.RESULTS After adjustments for age and gender,significant positive correlations were observed between the biomarkers CysC,RBP-4,α2-MG/urinary creatinine(UCr),PCX/UCr,and AFU/UCr,and clinical indicators such as urinary albumin-to-creatinine ratio(UACR),serum creatinine,urea,24-h total urine protein,and neutrophil-to-lymphocyte ratio(NLR).Conversely,these biomarkers exhibited negative correlations with the estimated glomerular filtration rate(P<0.05).Receiver operating characteristic(ROC)curve analysis further demonstrated the diagnostic performance of these biomarkers,with UACR showcasing the highest area under the ROC curve(AUC^(ROC))at 0.97.CONCLUSION This study underscores the diagnostic significance ofα2-MG,PCX,and AFU in the development of DN.The biomarkers RBP-4,CysC,PCX,AFU,andα2-MG provide promising diagnostic insights,while UACR is the most potent diagnostic biomarker in assessing DN.

Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study

BACKGROUND Diabetic nephropathy(DN)is a severe microvascular complication of diabetes characterized by inflammation,oxidative stress,and renal fibrosis.Asiaticoside(AC)exhibits anti-inflammatory,antioxidant,and anti-fibrotic properties,suggesting potential therapeutic benefits for DN.This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2(NRF2)/heme oxygenase-1(HO-1)antioxidant pathway.METHODS The effects of AC on high glucose(HG)-induced proliferation,inflammation,oxidative stress,and fibrosis were evaluated in rat glomerular mesangial cells(HBZY-1)in vitro.A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury,inflammation,oxidative stress,and fibrosis.The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model.RESULTS AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats,including reduced body weight,and elevated blood glucose,serum creatinine,blood urea nitrogen,and 24-h urine protein.Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin(IL)-6,IL-8,tumor necrosis factor-alpha,reactive oxygen species,and malondialdehyde levels while increasing superoxide dismutase activity.Additionally,AC suppressed the expression of fibrogenic markers such as collagen I,collagen IV,and fibronectin.AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase(Quinone)1 protein expression in renal tissues and HG-induced HBZY-1 cells.CONCLUSION AC improves DN by reducing inflammation,oxidative stress,and fibrosis through the activation of the NRF2/HO-1 signaling pathway.These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.

Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.

Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p

BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.

New perspectives in the management of diabetic nephropathy

Diabetic nephropathy(DN)is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events.Until recently,strict glycemic control and blockade of the renin-angiotensin system(RAS)constituted the mainstay of treatment of DN.However,randomized controlled trials showed that sodium-glucose cotransporter 2 inhibitors further reduce the progression of DN.Therefore,these agents are recommended in all patients with DN regardless of DN stage and HbA1c levels.Moreover,additional blockade of the RAS with finerenone,a selective non-steroidal mineralocorticoid receptor antagonist,was also shown to prevent both the decline of renal function and cardiovascular events in this population.Finally,promising preliminary findings suggest that glucagon-like peptide 1 receptor agonists might also exert reno-and cardioprotective effects in patients with DN.Hopefully,this knowledge will improve the outcomes of this high-risk group of patients.

Unleashing the pathological role of epithelial-to-mesenchymal transition in diabetic nephropathy: The intricate connection with multifaceted mechanism

Renal epithelial-to-mesenchymal transition(EMT)is a process in which epithelial cells undergo biochemical changes and transform into mesenchymal-like cells,resulting in renal abnormalities,including fibrosis.EMT can cause diabetic neph-ropathy through triggering kidney fibrosis,inflammation,and functional impair-ment.The diverse molecular pathways that drive EMT-mediated renal fibrosis are not utterly known.Targeting key signaling pathways involved in EMT may help ameliorate diabetic nephropathy and improve renal function.In such settings,un-derstanding precisely the complicated signaling networks is critical for develo-ping customized therapies to intervene in EMT-mediated diabetic nephropathy.

A Case of Diabetic Nephropathy with Refractory Gastroparesis and Review of the Literature

Background: Gastroparesis is one of the complications of diabetes mellitus, and long-term gastroparesis seriously affects patients quality of life. Most of the patients can be relieved after lifestyle improvement and medication, but refractory gastroparesis is difficult to relieve, and is still a challenge in clinical treatment. Aim: To report a case of a patient with diabetic nephropathy combined with refractory gastroparesis, and to analyse the mechanism, diagnosis, severity grading, treatment of refractory gastroparesis in conjunction with a review of the literature, and to investigate the causes of recurrent nausea and vomiting in diabetic nephropathy patients with refractory diabetic gastroparesis and the possible effective treatment options. Case Presentation: The patient was hospitalised for recurrent nausea and vomiting and diagnosed with diabetic nephropathy and gastroparesis. Symptoms recurred after medication and peritoneal dialysis, and the patients symptoms were relieved after multifaceted interventions. Conclusion: Diabetic nephropathy and refractory gastroparesis can both manifest as digestive tract symptoms, and in the face of this complex disease, it is necessary to analyse the various etiological factors and take comprehensive treatment measures.

Study on the Clinical Application of Nutritional Management Combined with Clinical Monitoring of Glycated Albumin in Diabetic Nephropathy Dialysis Patients

Objective:To explore the clinical application of nutritional management combined with clinical monitoring of glycated albumin(GA)in diabetic nephropathy(DN)dialysis patients.Methods:A total of 20 diabetic nephropathy dialysis patients admitted to the People’s Hospital of Guandu District from January 2022 to February 2023 were included in the study.They were randomly divided into a conventional group(n=10)and an observation group(n=10).The study evaluated the blood glucose control,nutritional status,dialysis efficacy,and quality of life scores of both groups.Results:Before the intervention,there were no significant differences in fasting plasma glucose(FPG),GA,serum albumin,body mass index(BMI),dialysis efficiency values,urea clearance rate,or quality-of-life scores between the two groups(P>0.05).After the intervention,the observation group showed significantly lower FPG and GA levels,higher serum albumin,dialysis efficiency values,urea clearance rate,and improved quality-of-life scores compared to the conventional group(P<0.05),with no difference in BMI(P>0.05).Conclusion:Nutritional management combined with clinical monitoring of glycated albumin has a significant effect on the clinical application of diabetic nephropathy dialysis patients.It can effectively improve patients’blood glucose control and nutritional status,reduce the risk of complications,and enhance the quality of life,demonstrating clinical value for broader application.