63% recorded by the amount of water consumed.Neuroblastoma (NB) is a heterogeneous tumor that is common in infants and young children. Long non-coding RNA X-inactive specific transcript (XIST) is implicated in NB advancement. Nevertheless, the role and regulatory mechanism by which XIST in NB are not fully elucidated. Expression levels of XIST, microRNA-375-5p (miR-375), and L1 cell adhesion molecular (L1CAM) were examined through quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, proliferation, and colony formation of NB cells were determined with flow cytometry, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), or cell colony formation assays.  https://www.selleckchem.com/products/valproic-acid.html  Cell apoptotic rate was detected with flow cytometry assay. The relationship between XIST or L1CAM and miR-375 was verified via dual-luciferase reporter assay. The level of L1CAM protein was examined through western blotting. The role of XIST in vivo was confirmed through xenograft assay. XIST and L1CAM were upregulated while miR-375 was downregulated in NB tissues and cells. XIST depletion repressed tumor growth in vivo and elevated radiosensitivity, arrested cell cycle progression, and impeded proliferation of NB cells in vitro. Mechanistically, XIST modulated L1CAM expression through competitively binding to miR-375. Furthermore, miR-375 inhibitor recovered XIST inhibition-mediated effects on the radiosensitivity and malignant behaviors of NB cells. Also, L1CAM overexpression reversed the effects of miR-375 enhancement on the cell cycle progression, proliferation, and radiosensitivity of NB cells. XIST downregulation repressed tumor growth and boosted radiosensitivity of NB via modulating the miR-375/L1CAM axis, indicating that XIST was a promising target for NB treatment.Antineoplastic drugs such as oxaliplatin (OXA) often induce memory and emotional deficits. At present, the mechanisms underlying these side-effects are not fully understood, and no effective treatment is available. Here, we show that the short-term memory deficits and anxiety-like and depression-like behaviors induced by intraperitoneal injections of OXA (4 mg/kg per day for 5 consecutive days) were accompanied by synaptic dysfunction and downregulation of the NR2B subunit of N-methyl-D-aspartate receptors in the hippocampus, which is critically involved in memory and emotion. The OXA-induced behavioral and synaptic changes were prevented by chronic oral administration of magnesium-L-threonate (L-TAMS, 604 mg/kg per day, from 2 days before until the end of experiments). We found that OXA injections significantly reduced the free Mg2+ in serum and cerebrospinal fluid (from ~ 0.8 mmol/L to ~ 0.6 mmol/L). The Mg2+ deficiency (0.6 mmol/L) upregulated tumor necrosis factor (TNF-α) and phospho-p65 (p-p65), an active form of nuclear factor-kappaB (NF-κB), and downregulated the NR2B subunit in cultured hippocampal slices. Oral L-TAMS prevented the OXA-induced upregulation of TNF-α and p-p65, as well as microglial activation in the hippocampus and the medial prefrontal cortex. Finally, similar to oral L-TAMS, intracerebroventricular injection of PDTC, an NF-κB inhibitor, also prevented the OXA-induced memory/emotional deficits and the changes in TNF-α, p-p65, and microglia. Taken together, the activation of TNF-α/NF-κB signaling resulting from reduced brain Mg2+ is responsible for the memory/emotional deficits induced by OXA. Chronic oral L-TAMS may be a novel approach to treating chemotherapy-induced memory/emotional deficits.
  This analysis evaluated the efficacy and safety of dulaglutide in Chinese patients with type2 diabetes (T2D) aged ≥ 60 and < 60years.
 
  This post hoc analysis included patients with T2D enrolled in two phase3 clinical trials AWARD-CHN1 (NCT01644500) and AWARD-CHN2 (NCT01648582) of dulaglutide 0.75 and 1.5mg. Patients were categorized into two groups (≥ 60 and < 60years). Efficacy outcomes (change in glycated hemoglobin [HbA1c], fasting blood glucose [FBG], and weight; percentage of patients achieving HbA1c target [< 7.0%]) and safety outcomes (incidence of hypoglycemia and gastrointestinal treatment-emergent adverse events [GI TEAEs]) at 26weeks were evaluated for each age group in both trials.
 
  A total of 766 patients (≥ 60years, n = 222; < 60years, n = 544) were included in the study. A similar reduction of HbA1c was observed in both age groups AWARD-CHN1, 1.5mg (least squares mean [LSM] 95% confidence interval [CI] ≥ 60years - 1.45% [- 1.69, - 1.21%] and < 60years - 1.43% [- 1.59, - 1.28%]) and 0.75mg (≥ 60years - 1.29% [- 1.53, - 1.05%] and < 60years - 1.18% [- 1.33, - 1.03%]); AWARD-CHN2, 1.5mg (≥ 60years - 1.60% [- 1.83, - 1.36%] and < 60years - 1.64% [- 1.80, - 1.49%]) and 0.75mg (≥ 60years - 1.31% [- 1.55, - 1.08%] and < 60years - 1.33% [- 1.48, - 1.17%]). Dulaglutide showed a reduction in HbA1c as early as 4weeks after initiation of treatment, which was maintained over 26weeks in both age groups. The percentage of patients achieving HbA1c target < 7.0% at 26weeks was also similar in both age groups. Incidence of hypoglycemia and GI TEAEs was low in each age group.
 
  Treatment with once-weekly dulaglutide improved glycemic control in patients with T2D aged ≥ 60years and < 60years and was well tolerated in older patients, suggesting it can be considered a safe and effective treatment option for use in older patients with T2D.
 
  AWARD-CHN1 (NCT01644500) and AWARD-CHN2 (NCT01648582).
 AWARD-CHN1 (NCT01644500) and AWARD-CHN2 (NCT01648582).
  The US Food and Drug Administration has approved orally administered 100-mg and 200-mg doses of lasmiditan for the acute treatment of migraine, with or without aura. Having a unique mechanism of action, lasmiditan is the first and only Food and Drug Administration-approved serotonin 5-HT
  receptor agonist.
 
  The objective of this study was to systematically evaluate the efficacy and safety of lasmiditan for the acute treatment of migraine in adult patients.
 
  We systematically searched PUBMED, EMBASE, and Cochrane Library databases. Any relevant articles published before 3 March, 2020 were collected. Inclusion criteria were (1) randomized clinical trials; (2) enrolled adult participants diagnosed with migraine; (3) compared lasmiditan at 100mg or 200mg with placebo; (4) enrolled more than 100 participants; and (5) provided any available data for predefined primary or secondary outcomes.
 
  Three high-quality, multi-centered randomized clinical trials with 4506 patients in total were included. We found that the use of lasmiditan was related to a significantly increased rate of pain freedom at 2h post-dose with 31.