Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

Adenosine monophosphate-activated protein kinase(AMPK) is a highly conserved serine/ threonine protein kinase which plays an important role in regulating energy metabolism of the systemic cells. Under stress conditions, such as ischemia and hypoxia, AMPK can be activated.Then it plays a neuroprotective role in regulating mechanisms such as oxidative stress, autophagy, apoptosis and neuroinflammation and so on. Researches have found that chronic cerebral hypoperfusion may be a major cause of vascular cognitive impairment(VCI).AMPK can exert neuroprotective effects on VCI by regulating the aforementioned pathological processes.Therefore, this article reviews the molecular biological characteristics of AMPK and its role and mechanism in VCI, with the aim of promoting further research on AMPK and making it a new target for VCI treatment.

Endothelial progenitor cells (EPCs) are immature endothelial cells that can proliferate and differentiate into mature endothelial cells. After vascular injury, EPCs migrate from the bone marrow to the ischemic area, participating in damaged endothelial repair and neovascularization, providing a new potential therapeutic approach for vascular diseases including ischemic stroke. This article reviews the feasibility and limitations of EPCs as potential therapeutic targets for ischemic stroke.

Post-stroke cognitive impairment (PSCI) directly affects the outcome of patients with stroke. Enlarged perivascular spaces (EPVS) suggest the impairment of brain clearance mechanism and may affect cognitive function. More and more studies have confirmed that the presence of EPVS will aggravate PSCI. This article reviews the relationship between EPVS and PSCI.

Objective:To explore the correlation between enlarged perivascular spaces and other imaging markers of cerebrovascular disease in patients with ischemic stroke.Methods:Totally 287 patients with ischemic stroke hospitalized in neurology department from January 2018 to January 2019 were selected. According to the severity of EPVS in different parts of the brain, the correlations between the severity of EPVS in different parts of the brain and cerebral microbleeds (CMBs), white matter hyperintensity (WMH), lacunar infarcts (LIs) were analyzed. SPSS 22.0 software was used for analysis. Chi-square test, independent sample t-test, rank-sum test and non parametric Mann-Whitney U test were used for group comparison, and Logistic regression analysis was used for multivariate analysis. Results:EPVS was common and severe in patients with ischemic stroke. Periventricular white matter hyperintensity(PWMH)( β=1.604, P<0.001, OR=4.971, 95% CI=2.015-12.263), CMBs ( β=1.224, P=0.018, OR=3.339, 95% CI=1.232-9.383) and LIs ( β=0.626, P=0.047, OR=1.871, 95% CI=1.009-3.470) were independent risk factors for BG-EPVS. PWMH ( r=0.614), DWMH ( r=0.622), LIs ( r=0.532) were positively correlated with the severity of BG-EPVS (all P<0.01). Conclusion:The imaging makers of CSVD are related to BG-EPVS, which can affect the severity of brain BG-EPVS in patients with ischemic stroke.

Objective:To explore the relationship between total MRI burden and serum homocysteine (Hcy) in patients with cerebral small vessel disease(CSVD), and to provide clues for disease prevention and treatment.Methods:A total of 370 inpatients with CSVD from the neurology department of hospital were consecutively enrolled from September 2016 to December 2018.The clinical data, including serum homocysteine(Hcy) levels were collected.Brain MRI data were collected, including the severity of white matter hyperintensities(WMH), lacune infarcts(LI), cerebral microbleeds(CMBs), and enlarged perivascular spaces(ePVS) to evaluate the total load of CSVD.SPSS21.0 was applied to analyze the association between total CSVD burden and Hcy.Results:(1)Compared with the patients with lower Hcy levels, the higher Hcy group had heavier total burdens of CSVD( P<0.01). (2)According to the total MRI burden scores of CSVD, all patients were further divided into low burden group(106 cases) and moderate-high burden group(264 cases). Multivariate logistic regression analysis showed that Hcy( OR=1.026, 95% CI: 1.003-1.049, P=0.026) was risk factor for increasing CSVD burden and hyperhomocysteinemia was a stronger predictor for total MRI burdens of CSVD( OR=3.202, 95% CI: 1.947-5.268, P<0.001). Conclusion:Serum Hcy can be an independent risk factor for the total MRI burdens of CSVD.This finding provides a promising clue for the prediction and clinical management of CSVD.

Objective:To investigate the relationship between the enlarged of peripheral vascular space and cognitive function in patients with acute ischemic stroke.Methods:Totally 223 patients with first-episode acute cerebral infarction were selected from the department of neurology in Hebei general hospital from September 2016 to December 2018, who completed the test of cognitive function. All patients were divided into cognitive impairment group( n=67)and normal cognitive group( n=156)according to the score of MoCA.The risk factors of cognitive function and the relationship between the enlargement of perivascular space and cognitive function were analyzed by SPSS 21.0. Results:Age, history of coronary heart disease, Hcy, Fib, BG-EPVS and CSO-EPVS were statistically significant different in cognitive impairment group and normal cognitive group(all P<0.05). Age ( B=0.067, OR=1.070, 95% CI=1.035-1.106, P<0.05), Hcy( B=0.032, OR=1.033, 95% CI=1.007-1.060, P=0.013), and BG-EPVS( B=0.720, OR=2.055, 95% CI=1.041-4.055, P=0.038)were independent risk factors for cognitive impairment.The degree of BG-EPVS in the cognitive impairment group was negatively correlated with the total MoCA score( r=-0.332, P<0.05), visual space and execution( r=-0.256, P<0.01), attention( r=-0.256, P<0.01), language( r=-0.182, P<0.05)and orientation( r=-0.370, P<0.05). Conclusion:EPVS, especially BG-EPVS, can be used as an indicator to evaluate the early cognitive function of AIS patients.

Objective: To investigate the effect of metformin on autophagy in muscle cells exposed to palmitic acid, and to explore its mechanism. Methods: L6 rat myoblasts were incubated with palmitic acid at various concentrations(0.1, 0.2, 0.4, 0.6 mmol/L) and metformin(0.5, 1, 2, 5, 10 mmol/L) for 24 h. CCK8 method was used to detect the survival rate of muscle cells. After muscle cells were treated with palmitic acid and metformin for 24 h, mRNA and protein expressions of microtubule-associated protein11ight chain3(LC3Ⅱ), Beclin 1, p62, and silent mating type information regulation2 homolog-3(SIRT3) were detected by RT-PCR and Western blot, respectively. AMP-activated protein kinase(AMPK) phosphorylation level was detected by Western blot. Results: Palmitic acid dose-dependently decreased the survival rate of muscle cells, which was attenuated by metformin at the concentration of 2 mmol/L. After muscle cells were incubated with 0.4 mmol/L palmitic acid and 2 mmol/L metformin for 24 h, palmitic acid significantly reduced the mRNA and protein expressions of LC3Ⅱ, Beclin1, and SIRT3 as well as phosphorylation level of AMPK(all P<0.05), and increased p62 mRNA and protein expressions(P<0.05). Those effects were all antagonized by metformin(all P<0.05). Conclusions Metformin treatment may promote the autophagy of muscle cells exposed to palmitic acid through AMPK/STRT3 pathway.

Perivascular spaces (PVS) are an important part of the glymphatic system of the brain.Enlarged PVS (EPVS) may be an early manifestation of brain microvascular diseases and brain clearance mechanism disorders.There is growing evidence that EPVS plays an important role in the development and progression of cognitive impairment and may be its early warning sign.This article reviews the relationship between EPVS and cognitive impairment.

More and more studies have found that diabetes is closely related to white matter hyperintensities. This article reviews the relationship between diabetes and white matter hyperintensities, the effect of white matter hyperintensities on cognitive impairment in patients with diabetes, and the relationship between the two and stroke.