Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

Objective To investigate the neuroprotective effects and mechanisms of the alcoholic extract of the Yi drug(Rubia yunnanensis)on the Alzheimer's disease(AD)model of Caenorhabditis elegans(C.elegans).Methods Based on a transgenic C.elegans model of AD,the efficacy and mechanism of alcoholic extracts of Rubia yunnanensis against β-amyloid(Aβ)-induced toxic effects were explored.C.elegans were synchronized and divided into a control group and low and high dose groups of the alcoholic extract of Rubia yunnanensis to study the effects of the alcoholic extract of Rubia yunnanensis on C.elegans paralysis,lifespan,lipofuscin levels,behavior,growth and development,heat stress and oxidative stress,ROS levels,and Aβ aggregation,as well as the key transcription factors in the insulin/insulin-like growth factor 1 signaling pathway were investigated by GFP reporter gene worm assay and RNAi assay DAF-16 expression.Results Compared with the Control group,the intervention of the alcoholic extracts of Rubia yunnanensis could effectively improve the paralyzed phenotype of C.elegans(P<0.001),prolong the lifespan of C.elegans and reduce the level of lipofuscin in C.elegans significantly(P<0.001),improve the mobility of C.elegans significantly(P<0.001),and improve its resistance to oxidative stress and heat stress damage significantly(P<0.001),and reduce the level of ROS in C.elegans significantly(P<0.001),and reduce the deposition of Aβ protein in the head of C.elegans significantly(P<0.01),and had no effect on the growth and development of C.elegans(P>0.05),and also promoted the nuclear translocation of DAF-16 in the reporter gene C.elegans TJ356,and the effect of the alcoholic extracts of Rubia yunnanensis in delaying the degree of paralysis of C.elegans was lost after silencing the expression of C.elegans DAF-16 by RNAi,whereas the L4440 empty vector control group in the administration of Rubia yunnanensis alcohol extract significantly reduced the level of C.elegans paralysis(P<0.001).Conclusion The alcoholic extract of Rubia yunnanensis can significantly ameliorate the paralyzed phenotype in the C.elegans model of Alzheimer's disease with certain antioxidant,anti-aging and anti-Aβ protein activities,and the mechanism may be related to the activation of DAF-16,a downstream transcription factor of the insulin signaling pathway.

Objective:To evalaute the prevalence and determinants of thyroid nodules in children and adolescents in Jiangsu Province.Methods:This study included in-school students aged 8-17 years and selected through stratified cluster random sampling in Jiangsu. Thyroid nodule was diagnosed when its diameter was ≥3 mm. Random urine samples were collected for the detection of urinary iodine concentration with arsenic-cerium catalytic spectrophotometry. Data were analyzed by using χ2 test and logistic regression model. Results:In the 8 201 children and adolescents selected, the thyroid nodule detection rate was 16.10%. Multivariate logistic regression analysis revealed that, compared with those with urinary iodine levels of 100-299 μg/L, boys, those with normal body weight, those who were satisfied with their school performance, urinary iodine concentration ≥300 μg/L ( OR=1.15, 95% CI: 1.01-1.31), being girls ( OR=1.42, 95% CI: 1.26-1.60), being overweight ( OR=1.27, 95% CI: 1.07-1.50), being obese ( OR=1.23, 95% CI: 1.03-1.47), and dissatisfied with school performance ( OR=1.22, 95% CI: 1.04-1.43) were associated with higher likelihood of thyroid nodule detection. Children and adolescents who had solid snacks 2 times per week to 2 times per month ( OR=0.86, 95% CI: 0.74-0.99) or less than 2 times per month ( OR=0.80, 95% CI: 0.68-0.93) were more likely to have lower detection rate compared with those who had solid snacks more than 2 times per week. The detection rate of thyroid nodule increased with age ( OR=1.09, 95% CI: 1.06-1.11). Conclusion:The main factors influencing the detection rate of thyroid nodule in children and adolescents aged 8-17 years in Jiangsu included gender, age, urinary iodine concentration, BMI, self-assessed school performance and dietary habit.

Objective To explore the mechanism of Yishen Jiangtang Decoction(YSJTD)in improving diabetic kidney disease(DKD)based on the apoptotic Bcl-2/Caspase-3 pathway mediated by endoplasmic reticulum stress(ERS).Methods Thirty 8-week-old SPF male db/db mice were used to establish the DKD model and were randomly divided into model,YSJTD,ERS inhibitor(4-phenylbutyric acid[4-PBA]),and control groups(db/m mice),with 10 mice per group.Mice in the YSJTD and 4-PBA groups were gavaged daily with 5.6 mg/(g·d)YSJTD or 0.5 mg/(g·d)4-PBA,respectively,whereas the model and control groups received sodium carboxymethyl cellulose.Each mouse was orally administered 0.01 mL/(g·d)for 8 weeks.The mice were administered 0.01 mL/(g·d)YSJTD or 0.5mg/(g·d)4-PBA via gavage for 8 weeks.The general condition of the mice was observed,and blood glucose and plasma lipid levels were measured.Oral glucose tolerance tests(OGTT)and insulin tolerance tests(ITT)were performed,and the area under the curve(AUC)was calculated.Renal pathological changes(assessed using hematoxylin and eosin,periodic acid-Schiff,and Masson staining)and cell apoptosis,evaluated via TUNEL staining,were examined.Protein expression levels of Caspase-3 and Bcl-2 in kidney tissues were analyzed using Western blotting.A DKD model was established using high-glucose-induced mouse glomerular mesangial cells,SV40 MES 13.The Cell Counting Kit-8 assay was used to screen for high glucose concentrations and to determine the concentration of the YSJTD drug-containing serum.Cells were divided into four groups:control,model(30 mmol/L high glucose),10％YSJTD drug-containing serum(30 mmol/L high glucose+10％drug-containing serum),and 1 mol/L 4-PBA(30 mmol/L high glucose+1 mmol/L 4-PBA).Western blotting was used to detect the protein levels of GRP78,Caspase-3,and Bcl-2 in the cells.Results Compared to the control group,the model,YSJTD,and 4-PBA groups exhibited significantly increased OGTT-AUC,ITT-AUC,triglyceride(TG),and cholesterol(CHOL)levels(P＜0.05).These groups also showed severe renal pathological damage,increased glycogen deposition,and exacerbated fibrosis in kidney tissues.Compared to the model group,both the YSJTD and 4-PBA groups showed significantly reduced OGTT-AUC,TG,and CHOL levels,alleviated renal pathological damage,and decreased glycogen deposition and fibrosis.The YSJTD group also exhibited significantly reduced ITT-AUC(P＜0.05).Compared to the control group,the model group exhibited an increased number of apoptotic cells in renal tissue,reduced Bcl-2 expression,and elevated Caspase-3 expression(P＜0.05).Compared to the model group,both the YSJTD and 4-PBA groups demonstrated a reduced number of apoptotic cells,decreased Caspase-3 expression,and increased Bcl-2 expression,with the YSJTD group showing a more pronounced decrease in apoptotic cells(P＜0.05).In vitro experiments revealed that,compared to the control group,the model group exhibited increased GRP78 and Caspase-3 expression,as well as decreased Bcl-2 expression(P＜0.05).Compared to the model group,the 10％YSJTD drug-containing serum and 1 mol/L 4-PBA groups showed reduced GRP78 and Caspase-3 expression,as well as upregulated Bcl-2 expression(P＜0.05).Conclusion YSJTD improves glucose and lipid metabolism disorders in DKD by inhibiting the ERS-induced apoptotic pathway mediated by Bcl-2/Caspase-3,thereby exerting protective effects on renal function.

Type Ⅳ cardiorenal syndrome(CRS)is a subtype of CRS characterized by cardiac structural damage and/or functional decline secondary to chronic kidney disease.Clinically,it often manifests as fatigue,shortness of breath,edema,oliguria,and difficulty lying flat at night,which align with the TCM pattern of"deficiency of primordial qi and excess of yin-pathogenic fire".Li Dongyuan proposed the theory that"yin-pathogenic fire and primordial qi are opposites",emphasizing the dynamic relationship of"mutual growth and decline"between primordial qi and yin fire.From this perspective,the development and progression of Type Ⅳ CRS are believed to correspond to the fluctuations in the balance of primordial qi and yin-pathogenic fire.Based on this theory,the core pathogenesis of Type Ⅳ CRS is summarized as"imbalance between qi and fire",where"deficiency of primordial qi"is the root cause,often attributed to damage to the heart,spleen,and kidney,while"exuberance of yin-pathogenic fire"represents the pathological manifestation.In clinical practice,the treatment should focus on reinforcing primordial qi and subduing yin-pathogenic fire,with tailored approaches according to the stages of disease progression.In the early stage,when primordial qi lacks a foundation for generation and yin-pathogenic fire begins to emerge,the treatment should aim to consolidate the root of primordial qi and suppress the budding of yin-pathogenic fire.In the middle stage,when primordial qi is insufficiently produced and yin-pathogenic fire becomes predominant,the treatment should focus on nourishing the source of primordial qi and curbing the exuberance of yin-pathogenic fire.In the late stage,when primordial qi becomes dispersed and yin-pathogenic fire is unconstrained,the treatment should prioritize consolidating the foundation of primordial qi and restraining the chaotic movement of yin-pathogenic fire.

Type Ⅳ cardiorenal syndrome(CRS)is a subtype of CRS characterized by cardiac structural damage and/or functional decline secondary to chronic kidney disease.Clinically,it often manifests as fatigue,shortness of breath,edema,oliguria,and difficulty lying flat at night,which align with the TCM pattern of"deficiency of primordial qi and excess of yin-pathogenic fire".Li Dongyuan proposed the theory that"yin-pathogenic fire and primordial qi are opposites",emphasizing the dynamic relationship of"mutual growth and decline"between primordial qi and yin fire.From this perspective,the development and progression of Type Ⅳ CRS are believed to correspond to the fluctuations in the balance of primordial qi and yin-pathogenic fire.Based on this theory,the core pathogenesis of Type Ⅳ CRS is summarized as"imbalance between qi and fire",where"deficiency of primordial qi"is the root cause,often attributed to damage to the heart,spleen,and kidney,while"exuberance of yin-pathogenic fire"represents the pathological manifestation.In clinical practice,the treatment should focus on reinforcing primordial qi and subduing yin-pathogenic fire,with tailored approaches according to the stages of disease progression.In the early stage,when primordial qi lacks a foundation for generation and yin-pathogenic fire begins to emerge,the treatment should aim to consolidate the root of primordial qi and suppress the budding of yin-pathogenic fire.In the middle stage,when primordial qi is insufficiently produced and yin-pathogenic fire becomes predominant,the treatment should focus on nourishing the source of primordial qi and curbing the exuberance of yin-pathogenic fire.In the late stage,when primordial qi becomes dispersed and yin-pathogenic fire is unconstrained,the treatment should prioritize consolidating the foundation of primordial qi and restraining the chaotic movement of yin-pathogenic fire.

Objective To explore the mechanism of Yishen Jiangtang Decoction(YSJTD)in improving diabetic kidney disease(DKD)based on the apoptotic Bcl-2/Caspase-3 pathway mediated by endoplasmic reticulum stress(ERS).Methods Thirty 8-week-old SPF male db/db mice were used to establish the DKD model and were randomly divided into model,YSJTD,ERS inhibitor(4-phenylbutyric acid[4-PBA]),and control groups(db/m mice),with 10 mice per group.Mice in the YSJTD and 4-PBA groups were gavaged daily with 5.6 mg/(g·d)YSJTD or 0.5 mg/(g·d)4-PBA,respectively,whereas the model and control groups received sodium carboxymethyl cellulose.Each mouse was orally administered 0.01 mL/(g·d)for 8 weeks.The mice were administered 0.01 mL/(g·d)YSJTD or 0.5mg/(g·d)4-PBA via gavage for 8 weeks.The general condition of the mice was observed,and blood glucose and plasma lipid levels were measured.Oral glucose tolerance tests(OGTT)and insulin tolerance tests(ITT)were performed,and the area under the curve(AUC)was calculated.Renal pathological changes(assessed using hematoxylin and eosin,periodic acid-Schiff,and Masson staining)and cell apoptosis,evaluated via TUNEL staining,were examined.Protein expression levels of Caspase-3 and Bcl-2 in kidney tissues were analyzed using Western blotting.A DKD model was established using high-glucose-induced mouse glomerular mesangial cells,SV40 MES 13.The Cell Counting Kit-8 assay was used to screen for high glucose concentrations and to determine the concentration of the YSJTD drug-containing serum.Cells were divided into four groups:control,model(30 mmol/L high glucose),10％YSJTD drug-containing serum(30 mmol/L high glucose+10％drug-containing serum),and 1 mol/L 4-PBA(30 mmol/L high glucose+1 mmol/L 4-PBA).Western blotting was used to detect the protein levels of GRP78,Caspase-3,and Bcl-2 in the cells.Results Compared to the control group,the model,YSJTD,and 4-PBA groups exhibited significantly increased OGTT-AUC,ITT-AUC,triglyceride(TG),and cholesterol(CHOL)levels(P＜0.05).These groups also showed severe renal pathological damage,increased glycogen deposition,and exacerbated fibrosis in kidney tissues.Compared to the model group,both the YSJTD and 4-PBA groups showed significantly reduced OGTT-AUC,TG,and CHOL levels,alleviated renal pathological damage,and decreased glycogen deposition and fibrosis.The YSJTD group also exhibited significantly reduced ITT-AUC(P＜0.05).Compared to the control group,the model group exhibited an increased number of apoptotic cells in renal tissue,reduced Bcl-2 expression,and elevated Caspase-3 expression(P＜0.05).Compared to the model group,both the YSJTD and 4-PBA groups demonstrated a reduced number of apoptotic cells,decreased Caspase-3 expression,and increased Bcl-2 expression,with the YSJTD group showing a more pronounced decrease in apoptotic cells(P＜0.05).In vitro experiments revealed that,compared to the control group,the model group exhibited increased GRP78 and Caspase-3 expression,as well as decreased Bcl-2 expression(P＜0.05).Compared to the model group,the 10％YSJTD drug-containing serum and 1 mol/L 4-PBA groups showed reduced GRP78 and Caspase-3 expression,as well as upregulated Bcl-2 expression(P＜0.05).Conclusion YSJTD improves glucose and lipid metabolism disorders in DKD by inhibiting the ERS-induced apoptotic pathway mediated by Bcl-2/Caspase-3,thereby exerting protective effects on renal function.

Objective:To evalaute the prevalence and determinants of thyroid nodules in children and adolescents in Jiangsu Province.Methods:This study included in-school students aged 8-17 years and selected through stratified cluster random sampling in Jiangsu. Thyroid nodule was diagnosed when its diameter was ≥3 mm. Random urine samples were collected for the detection of urinary iodine concentration with arsenic-cerium catalytic spectrophotometry. Data were analyzed by using χ2 test and logistic regression model. Results:In the 8 201 children and adolescents selected, the thyroid nodule detection rate was 16.10%. Multivariate logistic regression analysis revealed that, compared with those with urinary iodine levels of 100-299 μg/L, boys, those with normal body weight, those who were satisfied with their school performance, urinary iodine concentration ≥300 μg/L ( OR=1.15, 95% CI: 1.01-1.31), being girls ( OR=1.42, 95% CI: 1.26-1.60), being overweight ( OR=1.27, 95% CI: 1.07-1.50), being obese ( OR=1.23, 95% CI: 1.03-1.47), and dissatisfied with school performance ( OR=1.22, 95% CI: 1.04-1.43) were associated with higher likelihood of thyroid nodule detection. Children and adolescents who had solid snacks 2 times per week to 2 times per month ( OR=0.86, 95% CI: 0.74-0.99) or less than 2 times per month ( OR=0.80, 95% CI: 0.68-0.93) were more likely to have lower detection rate compared with those who had solid snacks more than 2 times per week. The detection rate of thyroid nodule increased with age ( OR=1.09, 95% CI: 1.06-1.11). Conclusion:The main factors influencing the detection rate of thyroid nodule in children and adolescents aged 8-17 years in Jiangsu included gender, age, urinary iodine concentration, BMI, self-assessed school performance and dietary habit.

Objective To investigate the neuroprotective effects and mechanisms of the alcoholic extract of the Yi drug(Rubia yunnanensis)on the Alzheimer's disease(AD)model of Caenorhabditis elegans(C.elegans).Methods Based on a transgenic C.elegans model of AD,the efficacy and mechanism of alcoholic extracts of Rubia yunnanensis against β-amyloid(Aβ)-induced toxic effects were explored.C.elegans were synchronized and divided into a control group and low and high dose groups of the alcoholic extract of Rubia yunnanensis to study the effects of the alcoholic extract of Rubia yunnanensis on C.elegans paralysis,lifespan,lipofuscin levels,behavior,growth and development,heat stress and oxidative stress,ROS levels,and Aβ aggregation,as well as the key transcription factors in the insulin/insulin-like growth factor 1 signaling pathway were investigated by GFP reporter gene worm assay and RNAi assay DAF-16 expression.Results Compared with the Control group,the intervention of the alcoholic extracts of Rubia yunnanensis could effectively improve the paralyzed phenotype of C.elegans(P<0.001),prolong the lifespan of C.elegans and reduce the level of lipofuscin in C.elegans significantly(P<0.001),improve the mobility of C.elegans significantly(P<0.001),and improve its resistance to oxidative stress and heat stress damage significantly(P<0.001),and reduce the level of ROS in C.elegans significantly(P<0.001),and reduce the deposition of Aβ protein in the head of C.elegans significantly(P<0.01),and had no effect on the growth and development of C.elegans(P>0.05),and also promoted the nuclear translocation of DAF-16 in the reporter gene C.elegans TJ356,and the effect of the alcoholic extracts of Rubia yunnanensis in delaying the degree of paralysis of C.elegans was lost after silencing the expression of C.elegans DAF-16 by RNAi,whereas the L4440 empty vector control group in the administration of Rubia yunnanensis alcohol extract significantly reduced the level of C.elegans paralysis(P<0.001).Conclusion The alcoholic extract of Rubia yunnanensis can significantly ameliorate the paralyzed phenotype in the C.elegans model of Alzheimer's disease with certain antioxidant,anti-aging and anti-Aβ protein activities,and the mechanism may be related to the activation of DAF-16,a downstream transcription factor of the insulin signaling pathway.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.