Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

[Q]: Context: The fruits of Vitex rotundifolia L. are widely used to treat inflammation of the airway in Traditional Chinese medicine. Previous studies found that casticin, isolated from Vitex rotundifolia, could induce apoptosis of tumor cells. In this study, we evaluated the anti-inflammatory effects of casticin and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated macrophages.', 'RAW264.7 cells were pretreated with various concentrations of casticin (0.3-10μM), and then treated with LPS to induce inflammation. We assayed the levels of proinflammatory cytokines and prostaglandin E2 (PGE2) using ELISA, and examined the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and heme oxygenase (HO)-1 by Western blot. We also investigated the anti-inflammatory molecular mechanism by analyzing inflammatory-associated signaling pathways, including the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways.', 'We found casticin inhibited the levels of nitric oxide and PGE2, and decreased the production of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α). In addition, iNOS and COX-2 expression levels were suppressed and casticin increased HO-1 and Nrf2 production in a concentration-dependent manner. Furthermore, casticin significantly inhibited NF-κB subunit p65 proteins in the nucleus and decreased Akt and MAPK activation.
Answer: These results suggest that the anti-inflammatory effect of casticin is due to inhibition of proinflammatory cytokines and mediators by blocking the NF-κB, Akt, and MAPK signaling pathways.
[A]: Does casticin inhibit COX-2 and iNOS expression via suppression of NF-κB and MAPK signaling in lipopolysaccharide-stimulated mouse macrophages?


[Q]: Context: To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA).', "We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with ≥1 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models.", 'Of 113\u2005677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6\u2005months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6\u2005months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged ≥50\u2005years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3\u2005years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively.
Answer: Anti-TNF therapy was associated with a significantly lower risk of cardiovascular events among patients with RA, older patients with RA and patients without prior exposure to methotrexate.
[A]: Are longer durations of antitumour necrosis factor treatment associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis?


[Q]: Context: To explore the impact of titanium implant on the growth and development of pediatric mandible after suffering from mandibular fracture and undergoing open reduction and internal fixation (ORIF) compared with those that underwent titanium plate removal postoperatively.', "Fifteen pediatric patients with mandibular fracture who underwent ORIF were included in this study. Eight patients did not undergo titanium implant removal postoperatively, whereas the other seven patients underwent the routine. The postoperative data of the pediatrics were collected for comparative analysis by taking the patients' frontal and lateral photos, recording the inter-incisor distance, and measuring the height of mandibular ramus, length of the mandibular body, and combined length of the mandible in three-dimensional reconstruction image.", 'All patients had acceptable facial contour, mouth opening, and occlusion, without obvious abnormalities. The radiography showed no significant difference between the bilateral mandibular lengths in the two groups of patients (P>0.05).
Answer: The titanium plants have no significant impact on the growth and development of pediatric mandible postoperatively; hence, the question on whether the titanium plates should be removed or not may be neglected. The removal operation may lead to secondary trauma; thus, performing titanium plate removal routinely is not recommended.
[A]:
Do [ Long-term follow-up study of titanium implant impact on pediatric mandibular growth and development ]?