Deep medullary vein （DMV） lesions refer to the structural and functional abnormalities of the small venous system within the deep white matter under pathological conditions. Under normal physiological circumstances， DMV are responsible for venous drainage of deep white matter and clearance of metabolic waste. The pathogenesis of DMV lesions mainly involves luminal stenosis caused by collagen deposition in the venous wall， hemodynamic disturbances due to elevated venous pressure， functional impairment of the venous wall induced by inflammatory responses and cytokines， and microcirculatory disturbance caused by ischemia and hypoxia. Studies have shown that DMV lesions are extensively observed in various neurological disorders， including acute ischemic stroke， cerebral small vessel disease， multiple sclerosis， and Sturge-Weber syndrome， and are closely associated with the imaging manifestations， clinical progression， and prognosis of these diseases. However， despite the continuous improvement in the capability for DMV detection， the specific role of DMV in the pathogenesis of different diseases remains unclear. Further studies are needed to explore the role of DMV in pathophysiological processes and assess its clinical value as a target for early diagnosis and intervention， so as to facilitate the development of precision medicine.

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

OBJECTIVES: This study aimed to extend an epidemiological model (SEIHFR) to analyze epidemic trends, and evaluate intervention efficacy. METHODS: SEIHFR was modified to examine disease transmission dynamics after vaccination for the Ebola outbreak. Using existing data from Liberia, sensitivity analysis of various epidemic scenarios was used to inform the model structure, estimate the basic reproduction number ℜ₀ and investigate how the vaccination could effectively change the course of the epidemic. RESULTS: If a randomized mass vaccination strategy was adopted, vaccines would be administered prophylactically or as early as possible (depending on the availability of vaccines). An effective vaccination rate threshold for Liberia was estimated as 48.74% among susceptible individuals. If a ring vaccination strategy was adopted to control the spread of the Ebola virus, vaccines would be given to reduce the transmission rate improving the tracing rate of the contact persons of an infected individual. CONCLUSION: The extended SEIHFR model predicted the total number of infected cases, number of deaths, number of recoveries, and duration of outbreaks among others with different levels of interventions such as vaccination rate. This model may be used to better understand the spread of Ebola and develop strategies that may achieve a disease-free state.
Africa, Western ; Basic Reproduction Number ; Disease Outbreaks ; Ebolavirus ; Humans ; Liberia ; Mass Vaccination ; Vaccination ; Vaccines

Objective To summarize the experience with cadaveric renal transplantation for improving the long-term survival rate of the recipients.Methods The clinical data of 1210 cases(773 men and 437 women;age range,6-75 years) of cadaveric kidney transplantation from 1986 to 2003 were analyzed retrospectively,including the resection of the donor's kidneys,surgical techniques,use of immunosuppressants,and complications.The 1210 patients underwent renal transplantation for most of them(1047 cases) suffered from chronic glomerulonephritis.Lymphocytotoxicity test was performed in 1210 cases with all