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 explore the influencing factors of early neurological deterioration(END)in patients with acute anterior circulation large-vessel occlusive mild stroke who were treated with medications alone within 72 h after onset.Methods Retrospective consecutive data were collected of patients with acute large-vessel occlusive mild stroke who presented to the Advanced Stroke Center of Linyi People's Hospital within 24 h of onset from January 2021 to December 2022.END was defined as an increase of ≥ 4 points in the National Institutes of Health stroke scale(N1HSS)score within 72 h after onset compared to the admission score.Patients were divided into the neurological deterioration group and the stable condition group(NIHSS score did not increase or increased by 1-3 points within 72 h after onset compared to the admission score).Baseline and clinical data of all patients were collected,including sex,age,cerebrovascular disease risk factors(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation,smoking,alcohol consumption,stroke history),NIHSS score at admission,time from onset to admission,systolic blood pressure at admission,diastolic blood pressure at admission,laboratory test indicators at admission(blood glucose,glycosylated hemoglobin,homocysteine,total cholesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,neutrophils,lymphocytes and neutrophil-to-lymphocyte ratio),responsible occlusion artery(internal carotid artery,middle cerebral artery,anterior cerebral artery),affected cerebral hemisphere,collateral circulation score,and medications used within 72 h after admission(intravenous thrombolysis+dual antiplatelet therapy,tirofiban+dual antiplatelet therapy,argatroban+dual antiplatelet therapy,argatroban alone,dual antiplatelet therapy alone).Variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to explore the independent influencing factors for END in patients with acute anterior circulation large-vessel occlusive mild stroke treated with medications alone.Results A total of 208 patients with acute anterior circulation large-vessel occlusive mild stroke were included,with 143 males and 65 females,aged 38-85 years,with an average age of(64±9)years.Among them,86 patients were in the neurological deterioration group and 122 in the stable condition group.(1)There were statistically significant differences between the neurological deterioration group and the stable condition group in terms of history of diabetes mellitus(39.5％[34/86]vs.17.2％[21/122]),smoking history(43.0％[37/86]vs.29.5％[36/122]),left cerebral hemisphere lesion(57.0％[49/86]vs.41.0％[50/122]),collateral circulation score(4[3,5]vs.5[4,5]),time from onset to admission(7.0[3.0,17.0]hvs.4.3[2.0,11.0]h),blood glucose at admission(7.4[5.8,10.0]mmol/L vs.6.7[5.8,7.7]mmol/L),neutrophil-to-lymphocyte ratio(3.8[2.4,5.1]vs.3.0[2.1,4.3]),dual antiplatelet therapy alone(19.8％[17/86]vs.6.6％[8/122]),and argatroban+dual antiplatelet therapy(8.1％[7/86]vs.29.5％[36/122];all P＜0.05).There were no statistically significant differences in the results of the remaining univariate analyses(all P＞0.05).(2)Multivariate Logistic regression analysis showed that diabetes mellitus(OR,2.674,95％CI 1.121-6.377,P=0.027)and left cerebral hemisphere vessel occlusion(OR,2.030,95％CI I.083-3.806,P=0.027)were independent risk factors for END in acute anterior circulation large-vessel occlusive mild stroke.Argatroban+dual antiplatelet therapy(OR,0.267,95％CI 0.116-0.613,P=0.002)and high collateral circulation score(OR,0.551,95％CI 0.368-0.824,P=0.004)were independent protective factors for END in acute anterior circulation large-vessel occlusive mild stroke.Conclusions Acute anterior circulation large-vessel occlusive mild stroke patients with diabetes mellitus or left cerebral hemisphere lesions are prone to END.The combination of argatroban and dual antiplatelet therapy and good collateral circulation can reduce the risk of END.

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.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

Objective The causal relationship between immune cells and hepatocellular carcinoma(HCC)risk was investigated using a two-sample Mendelian randomization method.Methods The datasets including 731 immune cells and HCC were obtained from the GWAS database and Finngen database,respectively.The stability and reliability of Mendelian randomization studies were evaluated by the MR-Egger regression,MR PRESSO,Cochran's Q test,and leave one out test.The inverse variance weighting,MR-Egger,weigh-ted median,simple mode and weighted mode were used to investigate the causal relationship between immune cells and HCC.Results A total of 4 immune cells were found to have a potential causal relationship with HCC,and the results were stable.The CD3+CD39+Treg,CD80+granulocyte and CD4+Treg were protective factors for HCC(OR=0.910,95%CI:0.852-0.972;OR=0.919,95%CI:0.865-0.975;OR=0.924,95%CI:0.873-0.978),while CD45+CD33+HLA-DR+CD14+marrow cells were a risk factor for HCC(OR=1.116,95%CI:1.033-1.204).Conclusion The CD3+CD39+Treg,CD80+granulocytes,and CD4+Treg are negatively associated with the risk of HCC,while CD45+CD33+HLA-DR+CD14+marrow cells are positively associated with the risk of HCC.

AIM:To establish a physiologically-based pharmacokinetic(PBPK)model for vitamin D in adults,aiming to provide guidance for the ratio-nal clinical use of vitamin D in individuals with vita-min D deficiency.METHODS:Relevant literature and databases were reviewed to obtain the physi-cochemical properties and pharmacokinetic param-eters of vitamin D3.The PBPK model for adult whole-body vitamin D was constructed,optimized,and predicted using PK-Sim? software.The model's predictive performance was evaluated using confi-dence intervals,goodness of fit,and fold error(FE).The effectiveness of commonly used clinical dosing regimens was assessed based on the final opti-mized model,and personalized dosing recommen-dations were provided.RESULTS:The established adult whole-body PBPK model for vitamin D had a goodness of fit R2 of 0.961,approaching 1,and the FE values for AUC0-∞ and Cmax were both within the range of 0.5 and 2,indicating that the constructed PBPK model possesses good data predictive capa-bility.CONCLUSION:A successful PBPK model for oral vitamin D3 in adults has been established,showing good predictive performance for single oral doses of vitamin D3.Single oral doses of vita-min D3(7 500 μg and 15 000 μg)are safe and effec-tive dosing regimens for improving vitamin D insuf-ficiency or deficiency in Asian adults.Regular moni-toring of vitamin D levels before and during treat-ment is recommended to achieve the optimal out-comes of personalized therapy.

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.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

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.

With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*