ObjectiveTo investigate the effects of lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） gene G501C on brain structure and cognitive function in patients with white matter hyperintensities （WMH）. MethodsA total of 118 patients with WMH were enrolled. All participants underwent T1-weighted and T2-fluid-attenuated inversion recovery （T2-FLAIR） MRI to assess gray matter structure and WMH burden， and completed the mini-mental state examination （MMSE） and Montreal cognitive assessment （MoCA）. Partial correlation and mediation analyses were performed to explore the impact of LOX-1 polymorphism on cognitive function. ResultsParticipants were divided into GG+GC group （n = 35） and CC group （n = 83）. The GG+GC group showed lower MMSE and MoCA scores （MMSE： P=0.003； MOCA： P=0.015）， as well as greater WMH burden （all P0.001）， compared with the CC group. Voxel-based morphometry （VBM） analysis revealed reduced left thalamic volume in the GG+GC group， which was correlated with cognitive scores （all P0.05）. Subregional thalamic analysis further showed volume reductions in the lateral， ventral， medial， and pulvinar thalamic regions （all P0.05） in the GG+GC group， all positively associated with cognitive performance （all P0.05）. Mediation analyses indicated that volumes of the medial and pulvinar thalamic regions mediated the association between genotype and cognitive function （MMSE， MoCA）， and that WMH volume mediated the effect on MoCA scores. ConclusionThe LOX-1 G501C polymorphism may indirectly affect cognitive function by influencing specific thalamic subregional volumes and white matter damage， suggesting a potential mediating role of thalamic structures between genetic background and cognitive impairment.

ObjectiveTo investigate the effects of different antiplatelet therapy regimens （aspirin versus clopidogrel at specific doses） on cognitive function， blood biomarkers and brain imaging biomarkers when used prophylactically in patients with cerebral small vessel disease （CSVD）. MethodsA randomized controlled trial was conducted involving 160 CSVD patients who were randomly assigned to four groups： aspirin group （ASA）， low-dose clopidogrel group （CLOP-50）， standard-dose clopidogrel group （CLOP-75）， and control group （HC）. Cognitive function ［auditory verbal learning test-immediate recall （AVLT-IR）， auditory verbal learning test-short-delay recall （AVLT-SDR）， auditory verbal learning test-long-delay recall （AVLT-LDR）， hamilton anxiety rating scale （HAMA）， and hamilton depression rating scale （HAMD）， ADL（activities of daily living scale ）， （ascertain dementia 8-item questionnaire，AD8）］， blood biomarkers ［platelet count （PLT） and mean platelet volume （MPV）］， and CSVD-related imaging biomarkers ［white matter hyperintensities （WMH） and cerebral microbleeds （CMB）］ were assessed in all groups at baseline and at the 6-month follow-up. ResultsAfter 6 months of treatment， within-group comparisons showed that， compared with baseline， the ASA group had significantly increased scores on the AVLT immediate recall （AVLT-IR）， short-delay recall （AVLT-SDR）， and long-delay recall （AVLT-LDR） （P<0.05）. The CLOP-75 group showed significantly decreased HAMA and HAMD scores （P<0.05）， along with a significant increase in AVLT-LDR scores （P<0.05）. The number of CMBs increased from baseline in both the ASA and CLOP-75 groups （P<0.05）， whereas no statistically significant changes in blood biomarkers were observed in either group. By contrast， the CLOP-50 and HC groups showed no significant changes in cognitive function， blood biomarkers， or CSVD-related imaging biomarkers compared with baseline （all P<0.05）. Comparisons between groups showed that the AVLT-LDR scores and the number of CMBs increased faster in the ASA group than in the HC group （β=-0.187， P=0.04； β=-0.805， P<0.001）. In addition， the rate of CMB increase was also faster in the ASA group than in the CLOP-50 group （β=-0.695， P<0.01）. The ADL scores increased faster in the HC group than in the ASA group （β=0.170， P=0.02）. The AD8 scores decreased faster in the CLOP-75 group than in the HC group （β=-0.128， P=0.04）， but the rate of CMB increase in the CLOP-75 group was also faster than that in the HC group （β=0.604， P=0.04）. ConclusionIn CSVD patients， aspirin 100 mg or clopidogrel 75 mg improves cognitive function but increases the risk of cerebral hemorrhage. Clopidogrel 50 mg shows no short-term clinical benefit or imaging improvement.

Objective To explore the molecular mechanism by which curcumin enhances the anti-tuberculosis function of macrophages through immune metabolic regulation mediated by liver X receptor α(LXRα)/ABCA1.Methods A model was established by infecting THP-1-derived macrophages with attenuated strain of Mycobacterium bovis(M.bovis).The control group,curcumin group,M.pavis group,M.pavis+LXRα agonist(T0901317)group,M.pavis+LXRα inhibitor(GSK2033)group,M.pavis+curcumin group,M.pavis+curcumin+GSK2033 group and M.pavis+curcumin+T0901317 group were set up.The protein and gene expressions of LXRα/ABCA1 were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The accumulation of lipid droplets was analyzed by Oil Red O staining and micro-assay.The lipid content of the supernatant was determined by a biochemical analyzer,and cell proliferation was assessed by the MTT method.Bacterial clearance capacity was evaluated by measuring intracellular bacterial load.Results Curcumin significantly upregulated the protein and gene expression of LXRα/ABCA1 in M.Bovis-infected macrophages,reduced intracellular lipid accumulation and promoted lipid efflux,while enhancing cell proliferation and reducing intracellular bacterial load(P<0.05,P<0.01).LXRα inhibitors could reverse the effect of curcumin,while agonists synergistically enhanced its effect.Correlation analysis showed that the expression of LXRα/ABCA1 in cells was negatively correlated with the intracellular bacterial load,while the lipid level was positively correlated with the intracellular bacterial load(P<0.01).Conclusion Curcumin activates the LXRα/ABCA1 pathway,coordinates the metabolic remodeling of macrophages and the enhancement of immune function,and forms a synergistic effect against tuberculosis,providing an experimental basis for the development of a novel host-directed treatment strategy for tuberculosis based on immune-metabolic regulation.

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 explore the molecular mechanism by which curcumin enhances the anti-tuberculosis function of macrophages through immune metabolic regulation mediated by liver X receptor α(LXRα)/ABCA1.Methods A model was established by infecting THP-1-derived macrophages with attenuated strain of Mycobacterium bovis(M.bovis).The control group,curcumin group,M.pavis group,M.pavis+LXRα agonist(T0901317)group,M.pavis+LXRα inhibitor(GSK2033)group,M.pavis+curcumin group,M.pavis+curcumin+GSK2033 group and M.pavis+curcumin+T0901317 group were set up.The protein and gene expressions of LXRα/ABCA1 were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The accumulation of lipid droplets was analyzed by Oil Red O staining and micro-assay.The lipid content of the supernatant was determined by a biochemical analyzer,and cell proliferation was assessed by the MTT method.Bacterial clearance capacity was evaluated by measuring intracellular bacterial load.Results Curcumin significantly upregulated the protein and gene expression of LXRα/ABCA1 in M.Bovis-infected macrophages,reduced intracellular lipid accumulation and promoted lipid efflux,while enhancing cell proliferation and reducing intracellular bacterial load(P<0.05,P<0.01).LXRα inhibitors could reverse the effect of curcumin,while agonists synergistically enhanced its effect.Correlation analysis showed that the expression of LXRα/ABCA1 in cells was negatively correlated with the intracellular bacterial load,while the lipid level was positively correlated with the intracellular bacterial load(P<0.01).Conclusion Curcumin activates the LXRα/ABCA1 pathway,coordinates the metabolic remodeling of macrophages and the enhancement of immune function,and forms a synergistic effect against tuberculosis,providing an experimental basis for the development of a novel host-directed treatment strategy for tuberculosis based on immune-metabolic regulation.

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 evaluate the clinical efficacy,safety,and potency ratio of microwave ablation(MW A)combined with percutaneous osteoplasty(POP)for the treatment of flat bone metastases.Methods A total of 57 patients with flat bone metastases complicated by intractable pain,who underwent MWA combined with POP(combination therapy)or only POP(pure POP therapy)at the Zhongshan Municipal People's Hospital of China between January 2016 and January 2023,were enrolled in this study.The combination therapy group had 36 patients and the pure POP therapy group had 21 patients.Visual analog scale(VAS),Oswestry Disability Index(ODI),quality of life assessment scale(QOL)were used to evaluate the preoperative and the postoperative different period efficacy,and the results were compared between the two groups.The procedure-related complications in both groups were recorded.Results The technical success rate in the 57 patients was 100％,and no serious postoperative complications occurred.The mean follow-up time was(4.7±1.3)months(range of 3.4-7.2 months).The preoperative and the postoperative one-day,one-week,one-month and 3-month VAS scores in the combination therapy group were(7.39±1.09)points,(6.53±1.17)points,(1.94±0.70)points,(1.11±0.66)points and(1.39±0.59)points respectively,which in the pure POP therapy group were(7.52±1.01)points,(6.81±0.66)points,(3.38±0.65)points,(2.33±0.56)points and(2.52±0.50)points respectively.One week after operation,the VAS scores in the combination therapy group and the pure POP therapy group were decreased by(5.44±1.32)points and(4.14±0.96)points respectively.The differences in the postoperative one-week(t=-7.62,P＜0.01),one-month(t=-7.28,P＜0.01)and 3-month(t=-7.58,P＜0.01)VAS scores between the two groups were statistically significant.The preoperative and the postoperative one-day,one-week,one-month and 3-month ODI scores in the combination therapy group were(44.33±2.91)points,(44.08±2.82)points,(15.92±3.04)points,(14.00±2.39)points and(16.08±3.61)points respectively,which in the pure POP therapy group were(45.67±3.03)points,(45.14±2.80)points,(22.38±3.09)points,(19.76±2.99)points and(22.10±3.10)points respectively.One week after operation,the ODI score in the combination therapy group was decreased by(28.42±4.23)points,which in the pure POP therapy group was decreased by(23.29±4.28)points.The differences in the postoperative one-week(t=-7.50,P＜0.01),one-month(t=-7.37,P＜0.01)and 3-month(t=-6.51,P＜0.01)ODI scores between the two groups were statistically significant.The preoperative and the postoperative one-day,one-week,one-month and 3-month QOL scores in the combination therapy group were(24.69±3.92)points,(26.06±3.05)points,(38.67±3.00)points,(40.25±3.42)points and(39.58±3.99)points respectively,which in the pure POP therapy group were(24.43±3.53)points,(26.76±3.05)points,(32.81±2.17)points,(33.95±2.68)points and(31.19±4.27)points respectively.One week after operation,the QOL score in the combination therapy group was increased by(13.97±4.88)points,which in the pure POP therapy group was increased by(8.38±4.50)points.The differences in the postoperative one-week(t=8.34,P＜0.01),one-month(t=7.56,P＜0.01)and 3-month(t=7.18,P＜0.01)QOL scores between the two groups were statistically significant.The mean operation cost in the combination therapy group was 10 480.43 Chinese yuan,which was higher than that in the pure POP therapy group.Conclusion For the treatment of flat bone metastases,both pure POP therapy and MWA combined with POP therapy are clinically safe and effective,which can significantly relieve pain and improve quality of life.Compared with pure POP therapy,the MWA combined with POP therapy is more effective but its medical cost is more expensive.

AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.