Breast cancer is one of the most common and fatal malignancies among women worldwide, and its treatment efficacy is often limited by drug resistance and the presence of undruggable targets. Traditional small-molecule drugs have difficulty effectively modulating certain critical targets such as transcription factors and non-coding RNAs, necessitating new therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) function by recruiting pathogenic proteins to the cellular ubiquitin-proteasome system, thereby inducing their specific degradation. In contrast, ribonuclease-targeting chimeras (RIBOTACs) utilize small-molecule ligands but bind to RNA and direct endogenous RNases to selectively degrade pathogenic RNA molecules. By employing a "degradation rather than inhibition" mechanism, targeting chimera technology broadens the druggable landscape and offers a novel precision therapeutic strategy for breast cancer, particularly for refractory and drug-resistant cases. This approach not only overcomes the limitations of traditional drugs, such as the absence of suitable binding sites or poor selectivity, but also reduces required dosages and potential adverse effects. Recent studies have preliminarily demonstrated the therapeutic potential of PROTACs and RIBOTACs in breast cancer, encompassing target design, mechanistic investigation, and preclinical as well as early clinical applications. Research into these technologies reveals their ability to tackle previously undruggable targets, thereby providing theoretical support for the development of safer and more effective precision therapies for breast cancer. In the future, with advances in drug delivery systems and clinical trials, PROTACs and RIBOTACs are expected to be used synergistically with immunotherapy and chemotherapy, offering breast cancer patients more promising comprehensive treatment options and potentially driving oncology toward broader intervention of undruggable targets.
Humans ; Breast Neoplasms/drug therapy* ; Female ; Proteolysis ; Ribonucleases/metabolism* ; Molecular Targeted Therapy/methods* ; Antineoplastic Agents/therapeutic use*

Objective To investigate the correlation between levels of intercellular adhesion molecule-1 (ICAM-1), platelet surface P-selectin (CD62P), and inflammatory factors and cerebral artery stenosis in patients with acute cerebral infarction (ACI). Methods A total of 305 patients with ACI complicated with cerebral artery stenosis admitted to Zhongwu Hospital of Suqian City and Xinyi People's Hospital from January 2021 to December 2023 were selected as the research subjects. According to the degree of cerebral artery stenosis, they were divided into grade I group (stenosis degree<50%, n=85), grade II group (stenosis degree of 50%-75%, n=128), and grade III group (stenosis degree>75%, n=92). Sixty-eight ACI patients without cerebral artery stenosis during the same period were included in the reference group. The levels of serum inflammatory factors [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8)], ICAM-1 and CD62P were compared among the four groups. Spearman analysis was used to analyze the correlation between each factor and degree of cerebral artery stenosis. Results The levels of CRP, TNF-α, IL-6, IL-8, ICAM-1 and CD62P in the grade I, II and III groups were higher than those in the reference group. The levels of these factors were higher in the grade II and III groups than those in the grade I group, while the levels of various factors were higher in the grade III group than those in the grade II group (P<0.05). Spearman analysis showed that CRP, TNF-α, IL-6, IL-8, ICAM-1, and CD62P were positively correlated with the degree of cerebral artery stenosis in patients with ACI complicated with cerebral artery stenosis (P<0.05). Conclusion The levels of serum inflammatory factors, ICAM-1 and CD62P are significantly correlated with cerebral artery stenosis degree in patients with ACI.

Objective:To explore the relationship between the morphology of the carotid siphon, its related risk factors, and cerebral blood flow perfusion in patients with arteriosclerotic cerebral small vessel disease (aCSVD), and provide imaging evidence for the etiology of aCSVD.Methods:A total of 130 aCSVD patients hospitalized in the Department of Neurology of the First People′s Hospital of Hefei from March 2022 to June 2024, all of whom underwent multimodal imaging assessments, were enrolled. The baseline data were collected, and the morphology of the carotid siphon was visually evaluated using post-processing of head and neck computed tomography angiography (CTA), which was categorized into U-type ( n=63), C-type ( n=32), and V-type ( n=35). Calcification degree was semi-quantitatively assessed based on transverse CTA images. Cerebral perfusion was measured using magnetic resonance arterial spin labeling. The relationship between different siphon segment morphologies, calcification degrees, their risk factors, and cerebral blood flow perfusion was analyzed using analysis of variance and multinomial Logistic regression. Results:Univariate analysis of the 3 siphon types showed significant differences in low-density lipoprotein cholesterol [U-type (2.44±0.84) mmol/L,V-type (2.21±0.57) mmol/L, C-type (2.89±1.07) mmol/L, F=5.578, P=0.005], calcification degree [Among the 63 cases in the U-type group, 19 cases (30.15%) had mild calcification, 20 cases (31.75%) had moderate calcification, and 24 cases (38.10%) had severe calcification; among the 35 cases in the V-type group, 20 cases (57.14%) had mild calcification, 10 cases (28.57%) had moderate calcification, and 5 cases (14.29%) had severe calcification; among the 32 cases in the C-type group, 12 cases (37.50%) had mild calcification, 14 cases (43.75%) had moderate calcification, and 6 cases (18.75%) had severe calcification; χ2=13.092, P=0.011], and total aCSVD load [modified aCSVD load score: U-type 4.00(1.00, 4.00),V-type 3.00(1.00, 4.00),C-type 2.00(2.00, 4.00), H=9.997, P=0.007]. Multivariate Logistic regression revealed that patients with U-shaped siphons had a significantly higher overall aCSVD load than those with C-shaped siphons, with a regression coefficient of 0.728, and a statistically significant difference ( OR=2.070 ,95% CI 1.026-4.178, P=0.042). Additionally, total brain and white matter cerebral blood flow were decreased in patients with U-type siphons compared to those with C-type and V-type, primarily involving bilateral superior frontal gyri, left orbital frontal gyrus, and left straight gyrus regions (false discovery rate correction, P<0.05). Conclusions:The imaging manifestations of aCSVD are closely related to the shape of the internal carotid artery siphon.The U type siphon is more likely to lead to hemodynamic changes, resulting in decreased global and regional cerebral blood flow, and demonstrating a higher overall burden of aCSVD, which has certain clinical reference value for assessing the etiology of aCSVD.

Cerebral small vessel disease (CSVD) is a leading cause of stroke and vascular cognitive impairment, with cerebral microbleeds (CMB) recognized as one of its key imaging biomarkers. The pathological mechanisms underlying CMB vary significantly depending on their anatomical location. In recent years, insulin resistance (IR), a hallmark of metabolic syndrome, has emerged as a critical area of research in understanding the pathogenesis of CMB. This review focuses on the following aspects: an overview of the pathophysiological mechanisms of CMB and their location-specific characteristics; a detailed discussion of the definition of IR and its clinical research advancements in relation to CMB; and a comprehensive analysis of the potential pathways through which IR contributes to CMB development, including exacerbation of amyloid-beta pathology, activation of the renin-angiotensin and sympathetic nervous systems, induction of inflammation and oxidative stress, and disruption of the blood-brain barrier. The evidence highlights that IR exerts both specific and shared effects on different types of CMB, offering valuable insights for the early detection, targeted intervention, and holistic management of CSVD.

Objective To analyze the cerebral angiographic characteristics of patients with central retinal artery occlusion(CRAO)and to study their prognosis.Methods A retrospective study was conducted,with 182 CRAO patients enrolled,who were treated at Xuanwu Hospital,Capital Medical University,the First Affiliated Hospital of Anhui Medical University,the Affiliated Suzhou Hospital of Anhui Medical University,and the People's Hospital of Shihezi City from January 1,2014,to June 1,2024.All patients underwent cerebral angiography within one month of onset.The baseline characteristics,treatment details,and follow-up data were collected.The Spearman rank correlation coefficient was used to evaluate the correlation between the characteristics of the ophthalmic artery and the ipsilateral carotid artery angiography,and Logistic regression analysis was performed to explore factors related to patient prognosis.Results Cerebral angiography results showed that 81.3％of patients had ocular blood supply from the ipsilateral internal carotid artery,12.1％from the ipsilateral external carotid artery,and 6.6％from the ipsilateral middle cerebral artery.Among the patients,80(44.0％)had varying degrees of stenosis or occlusion of the affected ophthalmic artery,with 69 patients(86.3％)showing stenosis at the origin of the ophthalmic artery.Additionally,135 patients(74.2％)had varying degrees of stenosis or occlusion of the ipsilateral carotid artery,with 110 patients(60.4％)showing stenosis at the carotid bulb,88 patients(48.3％)having unilateral carotid lesions,and 41 patients(22.5％)having multiple lesions.Correlation analysis indicated a significant correlation between the degree of stenosis in the ophthalmic artery and the carotid artery(r=0.76,P=0.006).Univariate and multivariate Logistic regression analyses revealed that the time from symptom onset to hospital admission(OR=0.93,95％CI:0.85-0.98,P=0.018),the grading of oxygenation-based hypoperfusion maculopathy(OHM)(OR=3.12,95％CI:1.09-6.34,P=0.005),intravenous thrombolysis(IVT)(OR=2.75,95％CI:1.08-5.35,P=0.031),and the absence of stenosis in the ophthalmic artery(OR=1.33,95％CI:1.02-3.41,P=0.026)were independent predictors of prognosis for CRAO patients.Conclusions The degree of stenosis in the ophthalmic artery is significantly correlated with the degree of stenosis in the carotid artery in CRAO patients.Time from symptom onset to hospital admission,OHM grading,IVT,and the absence of stenosis in the ophthalmic artery are independent factors influencing the prognosis of CRAO patients.

Objective To analyze the cerebral angiographic characteristics of patients with central retinal artery occlusion(CRAO)and to study their prognosis.Methods A retrospective study was conducted,with 182 CRAO patients enrolled,who were treated at Xuanwu Hospital,Capital Medical University,the First Affiliated Hospital of Anhui Medical University,the Affiliated Suzhou Hospital of Anhui Medical University,and the People's Hospital of Shihezi City from January 1,2014,to June 1,2024.All patients underwent cerebral angiography within one month of onset.The baseline characteristics,treatment details,and follow-up data were collected.The Spearman rank correlation coefficient was used to evaluate the correlation between the characteristics of the ophthalmic artery and the ipsilateral carotid artery angiography,and Logistic regression analysis was performed to explore factors related to patient prognosis.Results Cerebral angiography results showed that 81.3％of patients had ocular blood supply from the ipsilateral internal carotid artery,12.1％from the ipsilateral external carotid artery,and 6.6％from the ipsilateral middle cerebral artery.Among the patients,80(44.0％)had varying degrees of stenosis or occlusion of the affected ophthalmic artery,with 69 patients(86.3％)showing stenosis at the origin of the ophthalmic artery.Additionally,135 patients(74.2％)had varying degrees of stenosis or occlusion of the ipsilateral carotid artery,with 110 patients(60.4％)showing stenosis at the carotid bulb,88 patients(48.3％)having unilateral carotid lesions,and 41 patients(22.5％)having multiple lesions.Correlation analysis indicated a significant correlation between the degree of stenosis in the ophthalmic artery and the carotid artery(r=0.76,P=0.006).Univariate and multivariate Logistic regression analyses revealed that the time from symptom onset to hospital admission(OR=0.93,95％CI:0.85-0.98,P=0.018),the grading of oxygenation-based hypoperfusion maculopathy(OHM)(OR=3.12,95％CI:1.09-6.34,P=0.005),intravenous thrombolysis(IVT)(OR=2.75,95％CI:1.08-5.35,P=0.031),and the absence of stenosis in the ophthalmic artery(OR=1.33,95％CI:1.02-3.41,P=0.026)were independent predictors of prognosis for CRAO patients.Conclusions The degree of stenosis in the ophthalmic artery is significantly correlated with the degree of stenosis in the carotid artery in CRAO patients.Time from symptom onset to hospital admission,OHM grading,IVT,and the absence of stenosis in the ophthalmic artery are independent factors influencing the prognosis of CRAO patients.

Objective:To explore the relationship between the morphology of the carotid siphon, its related risk factors, and cerebral blood flow perfusion in patients with arteriosclerotic cerebral small vessel disease (aCSVD), and provide imaging evidence for the etiology of aCSVD.Methods:A total of 130 aCSVD patients hospitalized in the Department of Neurology of the First People′s Hospital of Hefei from March 2022 to June 2024, all of whom underwent multimodal imaging assessments, were enrolled. The baseline data were collected, and the morphology of the carotid siphon was visually evaluated using post-processing of head and neck computed tomography angiography (CTA), which was categorized into U-type ( n=63), C-type ( n=32), and V-type ( n=35). Calcification degree was semi-quantitatively assessed based on transverse CTA images. Cerebral perfusion was measured using magnetic resonance arterial spin labeling. The relationship between different siphon segment morphologies, calcification degrees, their risk factors, and cerebral blood flow perfusion was analyzed using analysis of variance and multinomial Logistic regression. Results:Univariate analysis of the 3 siphon types showed significant differences in low-density lipoprotein cholesterol [U-type (2.44±0.84) mmol/L,V-type (2.21±0.57) mmol/L, C-type (2.89±1.07) mmol/L, F=5.578, P=0.005], calcification degree [Among the 63 cases in the U-type group, 19 cases (30.15%) had mild calcification, 20 cases (31.75%) had moderate calcification, and 24 cases (38.10%) had severe calcification; among the 35 cases in the V-type group, 20 cases (57.14%) had mild calcification, 10 cases (28.57%) had moderate calcification, and 5 cases (14.29%) had severe calcification; among the 32 cases in the C-type group, 12 cases (37.50%) had mild calcification, 14 cases (43.75%) had moderate calcification, and 6 cases (18.75%) had severe calcification; χ2=13.092, P=0.011], and total aCSVD load [modified aCSVD load score: U-type 4.00(1.00, 4.00),V-type 3.00(1.00, 4.00),C-type 2.00(2.00, 4.00), H=9.997, P=0.007]. Multivariate Logistic regression revealed that patients with U-shaped siphons had a significantly higher overall aCSVD load than those with C-shaped siphons, with a regression coefficient of 0.728, and a statistically significant difference ( OR=2.070 ,95% CI 1.026-4.178, P=0.042). Additionally, total brain and white matter cerebral blood flow were decreased in patients with U-type siphons compared to those with C-type and V-type, primarily involving bilateral superior frontal gyri, left orbital frontal gyrus, and left straight gyrus regions (false discovery rate correction, P<0.05). Conclusions:The imaging manifestations of aCSVD are closely related to the shape of the internal carotid artery siphon.The U type siphon is more likely to lead to hemodynamic changes, resulting in decreased global and regional cerebral blood flow, and demonstrating a higher overall burden of aCSVD, which has certain clinical reference value for assessing the etiology of aCSVD.

Cerebral small vessel disease (CSVD) is a leading cause of stroke and vascular cognitive impairment, with cerebral microbleeds (CMB) recognized as one of its key imaging biomarkers. The pathological mechanisms underlying CMB vary significantly depending on their anatomical location. In recent years, insulin resistance (IR), a hallmark of metabolic syndrome, has emerged as a critical area of research in understanding the pathogenesis of CMB. This review focuses on the following aspects: an overview of the pathophysiological mechanisms of CMB and their location-specific characteristics; a detailed discussion of the definition of IR and its clinical research advancements in relation to CMB; and a comprehensive analysis of the potential pathways through which IR contributes to CMB development, including exacerbation of amyloid-beta pathology, activation of the renin-angiotensin and sympathetic nervous systems, induction of inflammation and oxidative stress, and disruption of the blood-brain barrier. The evidence highlights that IR exerts both specific and shared effects on different types of CMB, offering valuable insights for the early detection, targeted intervention, and holistic management of CSVD.

Objective To investigate the correlation between the methylenetetrahydrofolate reductase(MTHFR)C677T polymorphism and disease in the course of Alzheimer's disease(AD),as well as whether whether it is af-fected by APOE gene.Methods A total of 74 AD patients,85 aMCI patients and 81 healthy controls(HC)were included.The levels of serum homocysteine(Hcy),folate,and vitamin B12,as well as the genotypes of MTHFR C677T and APOE,were determined.Logistic regression analysis was conducted to explore the relationship between MTHFR C677T polymorphism and the risk of AD and aMCI,as well as in different APOE ε4 subgroups.Results Compared with HC group,the serum Hcy levels in AD group and aMCI group were significantly higher(P＜0.001,P＜0.001),while serum folate levels in aMCI group was significantly lower(P=0.017).The serum fo-late level was significantly lower(P=0.038)in individuals with the MTHFR TT genotype compared to those with CC and CT genotypes,while the serum Hcy level was significantly higher(P=0.002).Regression analysis showed that the MTHFR TT genotype might increase the risk of aMCI in the subgroup of APOE e4 non-carriers(OR=3.670,95％CI=1.077-12.509,P=0.038),but not in APOE e4 carriers.Conclusion MTHFR C677T polymorphism plays an important role in Hcy metabolism,which leads to increased serum Hcy levels and decreased folate levels.In APOE ε4 non-carriers,the MTHFR TT genotype may increase the risk of aMCI.

The process approach,a set of analytical methods used in neuropsychology,quantifies the word-list learning tests and conventional analytical methods and fully reflects the memory profile of the subject.Therefore,it is widely used in the memory assessment of patients with Alzheimer's disease(AD)and mild cognitive impair-ment(MCI).The common indices of process approach,such as learning slope,semantic clustering,serial position effects,discriminability,and response bias,are key components of memory assessment.This article re-views the application of common indices of process approach in memory assessment of AD and MCI patients and discusses the shortcomings and future research directions of process approach.