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.

ObjectiveThis paper aims to systematically summarize the construction methods and characteristics of Alzheimer's disease （AD） animal models， providing a reference for improving AD animal models. MethodsLiterature related to AD animal models published between January 2022 and April 2025 was retrieved from China National Knowledge Infrastructure （CNKI）， China Biomedical Literature Database （CBM）， Wanfang Data， and VIP Database. Information such as experimental animal species， month of age， sex， modeling methods， and period， as well as evaluation indicators， was collated， extracted， and imported into Microsoft Excel 2024 to establish the database. In addition， various modeling methods and detection means were summarized and compared. ResultsA total of 400 articles were included. Among the AD animal models， amyloid precursor protein/presenilin-1 （APP/PS1） mice were used most frequently， with a predominance of male animals. Typically， 3-4-month-old rats or 5-6-month-old mice were selected. The main modeling methods included natural aging， accelerated aging， surgical intervention， drug induction， and transgenic technology. The modeling period was mainly concentrated in a single day or 6-8 weeks. Detection indicators of the models focused on physiological， behavioral， pathological-morphological， and biochemical phenotypes. ConclusionThe construction methods of AD animal models are relatively mature， with multifactorial interventions effectively simulating human pathology， though certain limitations remain. By systematically reviewing and analyzing recent experimental literature of AD animal models， this study aims to provide theoretical support and a reference for further improving the construction of the AD animal model.

Starting from the intrinsic relationship between the glymphatic system and the core pathogenesis of vascular cognitive impairment （VCI）， including internal dampness， phlegm turbidity， and blood stasis， this paper explores clinical approaches to the diagnosis and treatment of VCI. Dysfunction of the kidney's role in governing water leads to the accumulation of dampness， phlegm turbidity， and blood stasis， which are key pathological mechanisms underlying the onset and progression of VCI. The glymphatic system participates in the circulation of cerebrospinal fluid within the central nervous system， and its impairment can result in reduced clearance of soluble metabolic waste products in the brain， a crucial factor contributing to VCI. It is proposed that the "kidney governing water" function is related to the glymphatic system， and that the cerebral collaterals correspond structurally to the glymphatic pathways. Clinically， therapies aimed at tonifying the kidney， resolving phlegm， activating blood circulation， and unblocking collaterals， such as modified Kaixin Powder （开心散）， which eliminates dampness and turbidity， transforms phlegm， restores consciousness， enhances cognition， and strengthens the brain， are commonly employed. These treatments may improve VCI prognosis by regulating glymphatic system function， providing a theoretical basis for the prevention and treatment of VCI with traditional Chinese medicine.

Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

Objective To introduce the modeling method of pendulum-like modified rat abdominal heart heterotopic transplantation model and evaluate the quality of the model. Methods An operator without transplantation experience performed 15 consecutive models, recorded the time of each step, changes in body weight and modified Stanford scores, and calculated the surgical success rate, postoperative 1-week survival rate and technical success rate. Ultrasound examinations was performed in 1 week postoperatively. Results The times for donor heart acquisition, donor heart processing, recipient preparation and transplantation anastomosis were (14.3±1.4) min, (3.5±0.6) min, (13.6±2.1) min and (38.3±5.2) min respectively. The surgical success rate was 87% (13/15), and the survival rate 1 week after operative was 100% (13/13). The improved Stanford score indicated a technical success rate of 92% (12/13), and the postoperative 1-week ultrasound examination showed that grafts with Stanford scores ≥3 had detectable pulsation and blood flow signals. Conclusions The pendulum-like modified rat abdominal heart heterotopic transplantation improved model further optimizes the operational steps with a high success rate and stable quality, may be chosen as a modeling option for basic research in heart transplantation in the future.

Objective:To reveal the coupling mechanism of beam temporal profile and tissue oxygen content on radical kinetics, further explain the potential biological basis of the FLASH effect, and provide a reference for beam optimization and treatment planning design of FLASH radiotherapy (FLASH-RT).Methods:TOPAS-nBio v3.0 was used to simulate the physical and chemical processes of electron beams in water, and a full-scale kinetic model was established covering the generation, diffusion, reaction, and quenching of free radicals such as hydroxyl radical (·OH) and hydrated electrons (e aq-). Under different beam temporal profiles (single pulse, multi-pulses, continuous wave irradiation) and different oxygen concentration conditions, the evolution dynamics of free radicals were systematically simulated. At the same time, the data on e aq- content were obtained by experimental measurement of laser absorption spectroscopy to verify the accuracy of the model prediction. Results:The changing trend of e aq- concentration measured in the experiment was highly consistent with the simulation result, verifying the reliability of the constructed model. The beam time structure had a significant impact on the peak value and duration of free radical concentration. The single-pulse structure can cause the free radicals to rapidly increase and then quickly quench in a short time, while the continuous or long-pulse structure can cause the radical concentration to remain at a high level for a long time. The evolution of ·OH was not sensitive to the oxygen environment, while e aq- are greatly affected by the oxygen environment. The scavenging efficiency of free radicals in a hypoxic environment was significantly decreased, leading to an enhanced accumulation of oxidative damage to biological macromolecules. The lifespan of e aq- in an oxygen-rich environment decreased rapidly. Conclusions:Radical kinetics are regulated by both the beam temporal profile and oxygen content. FLASH-RT can utilize single-pulse or multi-pulses intervals to form periodic windows, reducing normal tissue damage by efficiently scavenging free radicals through antioxidants, while free radicals in tumor tissues continuously accumulate and amplify damage, thus generating a selective protective effect.

BACKGROUND:Exercise interventions,recognized for their economic and non-pharmaceutical efficacy,have demonstrated the potential to upregulate brain-derived neurotrophic factor levels,thereby offering a therapeutic approach to the prevention and management of Parkinson's disease.However,the specific mechanisms by which exercise targeting brain-derived neurotrophic factor expression to delay Parkinson's disease onset and progression are not clear.OBJECTIVE:To explore the interplay between brain-derived neurotrophic factor and Parkinson's disease,to analyze the specific regulatory effect and mechanism of exercise on the expression of brain-derived neurotrophic factor in the pathological state of Parkinson's disease,to review the improvement effect of different exercise methods mediated by brain-derived neurotrophic factor on Parkinson's disease,to clarify the potential mechanism of exercise therapy targeting brain-derived neurotrophic factor in the prevention and treatment of Parkinson's disease,in order to provide a new theoretical basis for exercise prevention and treatment of Parkinson's disease.METHODS:A systematic literature review was conducted using"Parkinson's disease,brain-derived neurotrophic factor,neuroprotection,dopamine,neuronal apoptosis,neuroinflammation,and synaptic plasticity"as Chinese keywords,and"Parkinson's disease,BDNF,neuroprotection,neuroinflammation,and synaptic plasticity"as English keywords.Databases including CNKI,WanFang Data,PubMed,and Web of Science were searched for relevant articles published up to February 2024.Totally 98 core articles were selected based on inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Within the pathophysiological framework of Parkinson's disease,exercise has been shown to stimulate the release of the myokine Irisin and to specifically enhance brain-derived neurotrophic factor expression,counteracting kynurenine pathway metabolic dysregulation.(2)Aerobic activities,notably specialized forms such as Running on a Wheel with Electrical Stimulation(rotarod walking exercise)in animals and Nordic Walking in humans,along with multimodal exercise regimens,have been demonstrated to significantly enhance brain-derived neurotrophic factor expression.This upregulation is instrumental in ameliorating the motor symptoms associated with Parkinson's disease.Furthermore,brain-derived neurotrophic factor is implicated in the beneficial modulation of non-motor symptoms,including cognitive and sleep disturbances,through the practice of mind-body interventions like Tai Chi.(3)Exercise-induced high expression of brain-derived neurotrophic factor exerts a neuroprotective effect through several mechanisms:By upregulating the expression of anti-inflammatory cytokines such as interleukin-10,nerve growth factor-beta,and transforming growth factor-beta,and concurrently downregulating the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta,thereby suppressing the activation of microglia via the inhibition of the nuclear factor-kappa B signaling pathway,leading to a reduction in neuroinflammatory responses;by augmenting the activity of tyrosine hydroxylase,which facilitates the synthesis and release of dopamine.This is complemented by the inhibition of matrix metalloproteinase-3 and glycogen synthase kinase-3 beta,preventing the hyperphosphorylation of alpha-synuclein at serine 129,thus counteracting abnormal neuronal apoptosis.By inducing long-term potentiation and promoting the robust expression of post-synaptic density protein 95 and synaptophysin,thereby enhancing synaptic plasticity and exerting a neuroprotective influence that may delay the onset and progression of Parkinson's disease.(4)Considering the pivotal role of brain-derived neurotrophic factor in Parkinson's disease progression and treatment,targeted exercise therapies could advance"Exercise+Medicine"precision medicine for Parkinson's disease.However,current research is limited by a narrow focus on motor symptoms and a lack of diverse exercise protocols.There is a need for more comprehensive,longitudinal studies using varied exercise modalities to better understand and address non-motor symptoms in Parkinson's disease patients to improve the lack of research in the field of Parkinson's disease exercise prevention and treatment.

BACKGROUND:Janus micro/nanoparticles are widely used in the field of tissue engineering,drug delivery,cancer therapy,bioimaging,and sensing due to their shape,structure,and functional anisotropy.OBJECTIVE:To elucidate the cutting-edge applications of Janus micro/nanoparticles in biomedicine.METHODS:Relevant literature published between 2010 and 2024 was retrieved from CNKI,WanFang Data,PubMed,and Web of Science databases.Searches were conducted using Chinese search terms"Janus nanoparticle,Janus particle,dual-faced particle,drug delivery,cancer therapy,bioimaging,biosensing,tissue engineering"and English search terms"Janus nanoparticle,Janus particle,drug delivery,cancer therapy,biosensing,bioimaging,tissue engineering."A total of 69 articles were selected for review after screening,organizing,summarizing,and synthesizing.RESULTS AND CONCLUSION:Janus micro/nanoparticles can be classified into three major categories based on their basic material properties:organic,inorganic,and organic-inorganic composites.Synthetic strategies consist of shielding,self-assembly,phase separation,microfluidics,and nucleation and growth techniques.Janus micro/nanoparticles exhibit high-efficiency drug delivery through characteristics such as high drug loading,gated release,and autonomous motion.In addition to enhancing traditional cancer treatment modalities(radiation and chemotherapy),Janus micro/nanoparticles can also be applied to emerging cancer treatment methods such as cell immunotherapy,protein drugs,and ferroptosis.Janus micro/nanoparticles serve as contrast agents to enhance bioimaging modalities(CT,MRI,and ultrasound)for high-quality imaging,guiding diagnosis and treatment.Janus micro/nanoparticles are utilized in tissue engineering for delivering growth factors,enhancing mechanical properties of biomaterials,and exhibiting antibacterial effects.Researchers have successfully tailored Janus micro/nanoparticles with desired functionalities by combining different organic polymers and inorganic materials using various synthetic strategies,enabling applications in complex biomedical fields.Despite current advancements,reports on the application of Janus micro/nanoparticles in tissue regeneration,large-scale production,and human clinical trials are relatively limited.Therefore,further research efforts are needed in the development,synthetic strategies,clinical safety assessment,and translation of such materials.

Objective To explore the feasibility and precautions of small incision bile duct stone removal in primary hospitals in extremely high-altitude areas.Methods The experience of small incision biliary exploration and cholecystectomy under general anesthesia at primary hospitals during the author's medical aid to Xizang in the high-altitude areas of northern Xizang was summarized(from June 2022 to December 2022).Results A total of 11 cases of small incision common bile duct stone removal were completed.Abdominal drainage was performed in all patients,including 6 cases with T-shaped tubes and 5 cases with primary closure of the common bile duct.The patients recovered well after surgery and was discharged.Conclusion In extreme high-altitude areas,under the guidance of medical aid doctors,it is completely feasible for primary hospitals to carry out small incision bile duct stone removal by selecting appropriate cases,training surgical skills,and performing detailed preoperative preparation.

Objective To investigate the relationship between kinase insert domain receptor(KDR)rs2305948 polymorphism and clopidogrel resistance(CR)in patients with acute coronary syndrome after receiving percutaneous coronary intervention(PCI).Methods A total of 468 patients with acute coronary syndrome,who were admitted to the Zhangjiakou Municipal First Hospital of China from September 2022 to September 2023,were selected as the subjects of study.All patients received PCI treatment and took medication of clopidogrel after the treatment.The occurrence of CR was recorded.The factors influencing the occurrence of CR were analyzed.The clinical significance of KDR rs2305948 polymorphism in predicting CR in patients with acute coronary syndrome after receiving PCI was evaluated.Results Of 468 patients with acute coronary syndrome,116(24.79％)developed CR.Logistic multivariate regression analysis indicated that low-density lipoprotein cholesterol(LDL-C,95％CI=1.420-8.390,OR=3.452),type 2 vascular endothelial growth factor receptor(VEGFR-2,95％CI=1.374-8.118,OR=3.340),KDR rs2305948 T/T genotype(95％CI=1.677-9.905,OR=4.076),and T allele(95％CI=1.390-8.207,OR=3.377)were the independent factors influencing the occurrence of CR inpatients with acute coronary syndrome after receiving PCI(all P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity,specificity,and area under ROC curve(AUC)of the T/T genotype of KDR rs2305948 in predicting CR in patients with acute coronary syndrome after receiving PCI were 75.86％,70.45％,and 0.773(95％CI=0.666-0.880)respectively.Conclusion In patients with acute coronary syndrome after receiving PCI,the risk of developing CR is higher.The KDR rs2305948 polymorphism is correlated with CR in patients with acute coronary syndrome after receiving PCI,and it has a certain predictive value for CR.