Determinants of angiographic thrombus burden and impact of thrombus aspiration on outcome in young patients with ST-segment elevation myocardial infarction.

OBJECTIVES: We aimed to investigate the determinants of thrombus burden (TB) and the impact of thrombus aspiration (TA) on outcome in young adults with ST segment elevation myocardial infarction (STEMI). BACKGROUND: The determinants of TB in young STEMI patients are not fully understood now. METHODS: The 182 young (age ≤ 45 years) STEMI patients, who underwent coronary angiography and percutaneous coronary intervention (PCI) in our hospital from January 2013 to September 2016, were included. Angiographic TB and impact of TA on major adverse cardiac events (MACEs) were evaluated. Median clinical follow-up period was 875 (641-1,052) days. RESULTS: All patients were male, mean age was 40 ± 5 years. High thrombus burden (HTB) was evidenced in 100 (54.9%) patients. TA was performed in 62 out 100 (62%) patients with high TB (HTB) during PCI. The prevalence of hypertension was significantly higher in the HTB group than in the low thrombus burden (LTB) group (75 vs. 17%, P < 0.001). The proportion of smoking, alcohol consumption, and family history of premature coronary artery disease were similar between HTB and LTB groups. During follow-up, 2 patients died and 31 patients underwent repeat PCI. MACE rate was significantly higher in the HTB group than in the LTB group (24.0 vs. 9.8%, P = 0.012) and significantly lower in HTB patients with TA than HTB patients without TA (14.5 vs. 39.5%, P = 0.018). CONCLUSIONS: Hypertension is an independent determinant of HTB and TA could be considered as an effective therapeutic option in young male STEMI patients with HTB.

Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia.

Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG-PCL (mPEG-PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG-PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague-Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.

Effects of Renal Ischemic Postconditioning on Myocardial Ultrastructural Organization and Myocardial Expression of Bcl-2/Bax in Rabbits.

We investigated the cardioprotective effect of renal ischemic postconditioning (RI-PostC) and its mechanisms in a rabbit model. Rabbits underwent 60 min of left anterior descending coronary artery occlusion (LADO) and 6 h of reperfusion. The ischemia-reperfusion (IR) group underwent LADO and reperfusion only. In the RI-PostC group, the left renal artery underwent 3 cycles of occlusion for 30 seconds and release for 30 seconds, before the coronary artery was reperfused. In the RI-PostC + GF109203X group, the rabbits received 0.05 mg/kg GF109203X (protein kinase C inhibitor) intravenously for 10 min followed by RI-PostC. Light microscopy and electron microscopy demonstrated that the RI-PostC group showed less pronounced changes, a smaller infarct region, and less apoptosis than the other two groups. Bcl-2 and Bax protein expression did not differ between the IR and RI-PostC + GF109203X groups. However, in the RI-PostC group, Bcl-2 protein expression was significantly higher and Bax protein expression was significantly lower than in the other two groups (P < 0.05). Changes in heart rate and mean arterial pressure were also smaller in the RI-PostC group than in the other two groups. These results indicate that RI-PostC can ameliorate myocardial ischemia-reperfusion injury and increase the Bcl-2/Bax ratio through a mechanism involving protein kinase C.

Transforming growth factor (TGF)-ß-induced microRNA-216a promotes acute pancreatitis via Akt and TGF-ß pathway in mice.

BACKGROUND: Both transforming growth factor ß (TGF-ß) and MicroRNA-216a (miR-216a) were reported to be upregulated during acute pancreatitis (AP). Moreover, miR-216a can be induced by TGF-ß. AIM: This study aimed to investigate how TGF-ß and miR-216a involved in the pathogenesis of AP both in a mouse model and in rat pancreatic acinar AR42J cells. METHODS: Cerulein-induced AP mouse model was established and pretreated with a TGF-ß inhibitor, SB431542. Serum amylase, lipase, tumor necrosis factor (TNF)-α, interleukin 6 (IL-6), TGF-ß and histopathological changes of pancreas were determined. Expression of miR-216a was detected by quantitative real-time RT-PCR. Bioinformatics was utilized to predict the targets of miR-216a. Expression levels of phosphatase and tensin homolog (PTEN), mothers against decapentaplegic homolog 7 (Smad7), TGF-ß receptor I, total Akt and pAkt were detected by Western blot. RESULTS: SB431542 significantly decreased serum amylase, lipase, TNF-α, IL-6, TGF-ß, histopathological changes of pancreas and expression of miR-216a in cerulein-induced mouse (P < 0.05). TGF-ß induced miR-216a in AR42J cells. PTEN and Smad7 were identified to be the possible targets of miR-216a. Transfection of miR-216a mimics (or inhibitors) in AR42J cells downregulated (or upregulated) the expression of PTEN and Smad7, thus affected the expression of downstream pAkt and TGF-ß receptor I. The expression changes of these protein caused by miR-216a can be regulated by SB431542 both in mouse model and AR42J cells. CONCLUSIONS: TGF-ß promotes AP by inducing miR-216a targeting PTEN and Smad7, thus through PI3K/Akt and TGF-ß feedback pathway.

Elevated lipoprotein-associated phospholipase A2 is associated with progression of nonculprit lesions after percutaneous coronary intervention.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that hydrolyzes oxidized phospholipids to generate bioactive proatherogenic products. Nonculprit lesions have been assumed to contribute to the pathogenesis of recurrent acute coronary syndrome (ACS). The role of LP-PLA2 in the progression of nonculprit coronary lesions after successful percutaneous coronary intervention (PCI) remains unclear. Our study included 123 patients with ACS who underwent initial PCI and a long-term follow-up (mean interval, one year) with coronary angiography. Among them, 19 patients were diagnosed as the progression of nonculprit lesions, based on the presence of at least one of the following factors: (1) ≥ 10% reduction in the diameter of a preexisting ≥ 50% stenosis; (2) ≥ 30% reduction in the diameter of a < 50% stenosis; and (3) early-onset stenosis with ≥ 30% reduction in the diameter of a segment that was normal on the primary angiogram. Blood sampling was drawn from all patients at 12-14 hours after PCI. The ACS patients with progression had higher total cholesterol (4.47 ± 1.02 mmol/L vs. 3.59 ± 0.57 mmol/L, P < 0.05), higher levels of Lp-PLA2 activity (14.39 ± 6.13 nmol/min/ml vs. 8.86 ± 3.14 nmol/min/ml, P < 0.001) and a higher proportion of multi-vessel disease than those without progression. Multivariate logistic regression analysis showed that Lp-PLA2 activity (ß = 0.024, P = 0.005) was an independent predictor for rapid progression of nonculprit coronary lesions. In conclusion, elevated Lp-PLA2 activity is associated with rapid progression of nonculprit coronary lesions in ACS patients who underwent PCI.

[Analysis of 51 cases of medical disputes in death after percutaneous coronary intervention].

OBJECTIVE: To investigate the causes and features of medical disputes in percutaneous coronary intervention (PCI) in the cardiology and to provide references for forensic expert testimony and medical disputes prevention. METHODS: Fifty one disputed fatal cases in PCI were analyzed in terms of the cause of death, informed consent and medical operations retrospectively. RESULTS: Thirty five cases were due to medical negligence, 28 due to defect technical operation, 2 due to mistake medical management and 5 due to both defect technical operation and mistake medical management. CONCLUSION: The causes of PCI medical negligence are defect medical operation, violate medical disciplines and insufficiency of informed consent.