Effect of inhibiting malonyl-CoA decarboxylase on cardiac remodeling after myocardial infarction in rats.

OBJECTIVES: The objective of this study was to determine the effect of inhibiting malonyl-CoA decarboxylase (MCD) on cardiac remodeling following myocardial infarction (MI) in rats. We used an ultrasound (US)-mediated microbubble (MB) approach for targeted delivery of a microRNA (miRNA) interference plasmid to the myocardium to silence MCD expression. METHODS: Five pairs of RNA interference sequences were screened and ranked according to their highest inhibition rates in HEK293 cells. The plasmid with the highest inhibition rate was transfected by US into the rat myocardium after mixing with lipid MB. Twelve and 16 weeks after MI, cardiac function was measured by echocardiography, and glucose transporter-4 (GLUT-4) and high-energy phosphate levels were monitored in the myocardium before and after transfection. RESULTS: Ejection fraction (EF) decreased by 16% in the control MI group, while it decreased by 8% in the MCD inhibition group that utilized the US-mediated MB approach. Concomitant with the improved EF, high-energy phosphates were increased and lactic acid was decreased in the left ventricle (LV), with no changes in triglyceride or GLUT-4 levels. CONCLUSIONS: Inhibiting MCD by an US-mediated injection of miRNA into the rat myocardium increased energy reserves in the LV after MI, most likely by limiting lactic acidosis and improving cardiac function without increasing lipid toxicity.

Safety of Toll-like receptor 9 agonists: a systematic review and meta-analysis.

CONTEXT: The promising efficacy of Toll-like receptor 9 (TLR9) agonists for use against pathogenic infections, allergies, malignant neoplasms and autoimmunity have been demonstrated well in clinical studies, but the safety of TLR9 agonists is controversial. OBJECTIVE: In light of the safety concerns, we conducted a systematic review and meta-analysis of clinical studies of TLR9 agonists. METHODS: A systematic literature search was conducted. We selected studies in which the subjects were treated with a TLR9 agonist and in which the safety of the TLR9 agonist was monitored. We extracted data on adverse events (AEs) when available. A meta-analysis was performed to determine the commonest and clinical significant AEs observed in the controlled studies. RESULTS: Nine single-arm studies and 12 controlled studies met our selection criteria. Subjects treated with TLR9 agonists were at a higher risk of anemia (risk ratio [RR] 1.04, 95% confidence interval [CI]: 1.02-1.06), neutropenia (RR 1.16, 95% CI: 1.11-1.21), leukopenia (RR 1.16, 95% CI: 1.11-1.22), lymphopenia (RR 1.17, 95% CI: 1.10-1.25), thrombocytopenia (RR 1.20, 95% CI: 1.14-1.27), flu-like symptoms (RR 10.59, 95% CI: 3.66-30.66), diarrhea (RR 1.40, 95% CI: 1.18-1.67) and headache (RR 1.61, 95% CI: 1.26-2.06). Injection-site reactions, such as erythema, pain, pruritus and swelling, were mild to moderate. TLR9 agonist therapies have not been associated with clinically significant autoimmune diseases, and few deaths potentially attributable to TLR9 agonists have been reported. CONCLUSION: The toxicity of TLR9 agonists is generally acceptable, except when the agonist is combined with immunosuppressive agents in patients with advanced non-small-cell lung cancer.

[Clinical and pathological study of chordoma in the skull base].

OBJECTIVE: To study the clinical and pathological characteristics of chordoma in the skull base. METHOD: The clinical manifestation, radiological finding and pathological characteristics in 20 patients with skull base chordoma were reviewed. Among them, 7 were immunohistochemical stained for keratin, epithelial membrane antigen, vimentin, glial fibrillary acidic protein and desmen, 2 were studied by electron microscope. 19 patients received surgical resection(5 cases were assisted by nasal endoscope). Eleven patients received radiation therapy. All 19 patients were followed-up for 3-5 years after treatment. RESULTS: (1) Clinical type were divided into four types in this group according to symptoms, sign, imaging features, operation finding, the original places and the expansive direction of the tumor. Seller type 5 cases, clival type 9 cases, occipito-temproral type 2 cases and extent type 4 cases. One case with multiple cranial never palsies died due to the pressure on brain stem by the neoplasm, was autopsied prove lungs metastasis. 5 years survival rates were 65% and 35% respectively. (2) Vacuolated physaliferous cell is the pathology characteristic of chordoma. (3) Positive rate of epithelial marker antigens are higher than other mesenchymal neoplasms. Distended rough endoplasmic reticulum and filament were found within the cytoplasm under transmission electron microscope. CONCLUSION: Chordoma is a kind of low malignancy which express epithelial and mesenchymal characteristics. Vacuolated physaliferous cell is the characteristic Pathologic appearance. Immunohistiochemical stain is helpful in differential diagnosis. Complete excision is still technically impossible. Chordoma maintain high recurrence rate after surgery, with metastasis. Combined modality therapy include surgical operation and radiation could prolonged survival period.

[Extraction of ecdysterone from Stemmacantha uniflora].

OBJECTIVE: To optimize the conditions for the extraction of ecdysterone from Stemmacantha uniflora. METHODS: Conditions for the extraction were studied by three different methods as guided by the content of ecdysterone and solid material that present in the extract. RESULTS: Methanol was the best solvent, water the second, ethanol was greatly effected by concentration. Ultrasonic extraction had a good efficiency with short time. The time of cool extraction was too long, its efficiency was inferior to the other methods. CONCLUSION: The best methods for the extraction of ecdysterone from Stemmacantha uniflora was methanol reflux extraction.