Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

Objective To compare the ultrasound signs of symptomatic joint lesions in rheumatoid arthritis (RA) and gouty arthritis (GA), musculoskeletal ultrasound (MSUS) was utilized.Methods A retrospective analysis was performed for 85 hospitalized patients with RA and 55 hospitalized patients with GA in the same period, and the differences in general data, diseased joints and ultrasound signs between the two groups were compared.Re-sults The gender, age and diseased joints of the two groups were statistically significant (all P<0.05).The de-tection rate of knee joint lesions was the highest;the RA group had high sensitivity, high specificity of meniscal in-jury, and high diagnostic efficiency of bone erosion, while the diagnostic performance of the three combined ultra-sound signs of punctate strong echo, double track sign and tophi in the GA group was higher than that of any indi-vidual diagnosis, and the sensitivity and specificity were also higher.The course of disease in the RA group was positively correlated with bone erosion (P<0.05) , and the course in the GA group was positively correlated with tophi (P<0.05).Conclusion The ultrasound signs of RA and GA are different, and MSUS has good value in the diagnosis and differential diagnosis of the two.

A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30 mg/kg), allopurinol (20 mg/kg) or benzbromarone (20 mg/kg) were orally administered to mice for 7 days. On the 7th day, uric acid and creatinine in serum and urine, blood urea nitrogen (BUN), malondialdehyde (MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin (H&E) staining. Hepatic XOD, renal urate transporter 1 (URAT1), glucose transporter type 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP-binding cassette transporter G2 (ABCG2) were detected by Western blot and real time polymerase chain reaction (PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid (FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.

Objective To investigate the application of iohexol in enhanced CT scanning. Methods The total of 623 patients taking iohexol for enhanced CT scanning were sampled to record relevant data for reference. According to evaluation standards for rational use of contrast media,the risk factors,selection of contrast media,medication time,usage and dosage,and drug combination were analyzed statistically. Results Among 623 patients used iohexo for enhanced CT scanning,302 patients had the risk factors of adverse reaction(the incidence rate as 48.48%) and 115 patients received psychological intervention(the incidence rate as 18.46%).And 206 patients had been given with the reasonable fluid therapy before and after angiography(the incidence rate as 33.07%),there were only 124 patients who performed the renal function and urine routine examination 48-72 h before and after angiography(the incidence rate as 19.90%).And 33 patients occured allergic reaction with the incidence rate as 5.30%. Conclusion There existed irrational phenomenon in application of diodone in enhanced CT scanning.It is necessary to further standardize the clinical application of diodone and make complete measures for rational use of diodone.

Neurodegenerative diseases are complex nervous system disorders as a result of myelin damage,synapses loss and/ or neuron loss. The pathogenesis of these diseases is still not completely clear. Protein kinases play an important role in both normal nerve cells and neurodegenerative disorders. lnhibitors of protein kinases can effectively regulate the physiological function of nerve cells and prevent the development and progression of the disease. This article reviews protein kinases and their inhibitors involved in Alzheimer disease,Parkinson disease,Huntington disease and other neurodegenerative diseases.