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WHAT IS KNOWN AND OBJECTIVE Benefits and risks of restarting oral anticoagulants (OACs) in patients with atrial fibrillation after major bleeding remain unknown. A meta-analysis was performed to systematically evaluate the effects of restarting OACs on thromboembolism and bleeding events in these patients. METHODS Relevant studies were obtained via systematically search of PubMed, Cochrane's Library and Embase databases. A randomized-effect model was used to pool the results. Subgroup analyses according to the types of OACs and sites of reoccurred bleeding were performed. RESULTS AND DISCUSSION Seven retrospective cohort studies with 12 197 patients were included. Restarting OACs was associated with reduced risk of thromboembolism (risk ratio [RR]: 0.61, 95% confidence interval [CI]: 0.42-0.87; P = .007). Subgroup analyses showed that restarting warfarin reduced risk of thromboembolism (RR = 0.59, P = .05), but not for the new oral anticoagulants (NOACs; RR = 1.37, P = .18). Moreover, restarting OACs did not affect the risk of reoccurred bleeding (RR = 0.98, 95% CI: 0.74-1.30, P = .89). Similar results were found for warfarin and NOACs, as well as for reoccurred intracranial haemorrhage or gastrointestinal bleeding. In addition, restarting OACs was associated with significantly reduced risk of all-cause mortality (RR = 0.42, 95% CI: 0.33-0.52, P

Baicalin, one of the major flavonoids in Scutellaria baicalensis, possesses antioxidant and anti-inflammatory properties. However, the effects of baicalin on metabolic disorders and hepatic steatosis have not been investigated.Body weight was examined in high-fat diet (HFD)-fed rats with or without baicalin treatment. At the end of the experiment, serum biochemical parameters, liver histology and lipid profile were analyzed to assess whether the animals were suffering from metabolic disorders or hepatic steatosis. In the liver, the phosphorylation of AMP activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and the gene expression of some enzymes involved in lipogenesis were examined. The effects of baicalin on the phosphorylation of AMPK and lipid accumulation induced by high glucose in human hepatoma HepG2 cells were also examined.Baicalin (80 mg/kg) administered ip for 16 weeks suppressed body weight gain in HFD-fed rats. Weight reduction was accompanied by the reduction of visceral fat mass. Baicalin significantly decreased the elevated serum cholesterol, free fatty acid and insulin concentrations caused by the HFD. Baicalin also suppressed systemic inflammation by reducing the serum level of tumor necrosis factor alpha. Baicalin reduced hepatic lipid accumulation, enhanced the phosphorylation of AMPK and ACC and down-regulated genes involved in lipogenesis, including fatty acid synthase and its upstream regulator SREBP-1c. In HepG2 cells, baicalin (5 and 10 micromol/L) increased the phosphorylation of AMPK and decreased lipid accumulation following the addition of high glucose.Our study suggests that baicalin might have beneficial effects on the development of hepatic steatosis and obesity-related disorders by targeting the hepatic AMPK.

AMP-activated protein kinase (AMPK) plays an important role in mediating energy metabolism and is controlled mainly by two upstream kinases, LKB1 or Ca(2+)/calmodulin-dependent protein kinase kinase-β (CaMKKβ). Previously, we found that baicalin, one of the major flavonoids in a traditional Chinese herb medicine, Scutellaria baicalensis, protects against the development of hepatic steatosis in rats feeding with a high-fat diet by the activation of AMPK, but, the underlying mechanism for AMPK activation is unknown. Here we show that in two LKB1-deficient cells, HeLa and A549 cells, baicalin activates AMPK by α Thr-172 phosphorylation and subsequent phosphorylation of its downstream target, acetyl CoA carboxylase, at Ser-79, to a similar degree as does in HepG2 cells (that express LKB1). Pharmacologic inhibition of CaMKKβ by its selective inhibitor STO-609 markedly inhibits baicalin-induced AMPK activation in both HeLa and HepG2 cells, indicating that CaMKKβ is the responsible AMPK kinase. We also show that treatment of baicalin causes a larger increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), although the maximal level of [Ca(2+)](i) is lower in HepG2 cells compared to HeLa cells. Chelation of intracellular free Ca(2+) by EDTA and EGTA, or depletion of intracellular Ca(2+) stores by the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin abrogates baicalin-induced activation of AMPK in HeLa cells. Neither cellular ATP nor the production of reactive oxygen species is altered by baicalin. Finally, in HeLa cells, baicalin treatment no longer decreases intracellular lipid accumulation caused by oleic acid after inhibition of CaMKKβ by STO-609. These results demonstrate that a potential Ca(2+)/CaMKKβ dependent pathway is involved in the activation of AMPK by baicalin and suggest that CaMKKβ likely acts as an upstream kinase of AMPK in response to baicalin.