The most severe form of brain glioma, glioblastoma (GBM), is highly malignant and usually resistant to chemotherapy. Therefore, discovery of new targets for gene therapy is important. Using subtraction cloning, we identified the human N‐Myc downstream‐regulated gene 2 (hNDRG2), located at chromosome 14q11.2, as a gene that is significantly suppressed in GBM tissues. Semiquantitative RT‐PCR showed that the hNDRG2 gene transcript is expressed in normal brain tissue and low‐grade gliomas but is present at low levels in 15 of 27 (56%) human GBM tissues and all of the 6 human glioblastoma cell lines examined. Furthermore, transfection of human glioblastoma U373 and U138 cells with a cDNA encoding hNDRG2 markedly reduced the cell proliferation. Our findings provide the first evidence to suggest that hNDRG2 may play a role in glioblastoma carcinogenesis.

Background: Due to the lack of comprehensive evidence based on prospective studies, the efficacy and safety of Janus Kinase (JAK) inhibitors (including tofacitinib, ruxolitinib, baricitinib, ritlecitinib and brepocitinib) for alopecia areata (AA) are yet to be proved.Methods: The systematic review and meta-analysis was performed pursuant to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline and registered on PROSPERO (CRD42022303007).Results: Fourteen prospective studies (5 RCTs and 9 non-RCTs), enrolling a total of 1845 patients with AA, were included for quantitative analysis. In RCTs, oral JAK inhibitors resulted in higher good response rate compared with control (RR: 6.86, 95% CI: 2.91–16.16); topical JAK inhibitors did not show any difference compared with control (RR: 1.00, 95% CI: 0.31–3.18). In non-RCTs, the pooled rate of good response to oral, topical and sublingual JAK inhibitors were 63% (95% CI: 44%–80%), 28% (95% CI: 1%–72%) and 11% (95% CI: 1%–29%), respectively. The pooled recurrence rate in patients treated with JAK inhibitors was 54% (95% CI: 39%–69%), mainly due to the withdrawal of JAK inhibitors. In RCTs, no difference was found in the risk of experiencing most kind of adverse events; in non-RCTs, the reported adverse events with high incidence rate were mostly mild and manageable.Conclusion: JAK inhibitors are efficacious and generally well-tolerated in treating AA with oral administration, whereas topical or sublingual administration lacks efficacy. Subgroup analyses indicate that baricitinib, ritlecitinib and brepocitinib seem to have equal efficacy for AA in RCTs; ruxolitinib (vs. tofacitinib) and AA (vs. AT/AU) are associated with better efficacy outcomes in non-RCT. Due to the high recurrence rate after withdrawal of JAK inhibitors, continuous treatment should be considered to maintain efficacy.Systematic Review Registration: PROSPERO: CRD 42022303007

Pharmacy education in China focuses on pharmaceutical sciences, with the bachelor of science (BS) of pharmacy as the entry-level degree. Pharmacy practice curricula in these programs are centered on compounding, dispensing, pharmacy administration, and laboratory experiences, which are the traditional responsibilities for pharmacists. Additional graduate-level training is available at the master of science (MS) and the doctor of philosophy (PhD) levels, most of which concentrate on drug discovery and drug development research. Presently, the emphasis in practice is beginning to shift to clinical pharmacy. With this change, additional degree offerings are being developed to meet the growing demand for clinical pharmacists. There is also interest in developing more clinical skills in practicing pharmacists through additional non-degree training. The Ministry of Education is considering a proposal for an entry-level professional degree of master and/or doctor in clinical pharmacy similar to the doctor of pharmacy (PharmD) degree in the United States.

Objective: The aim of this article is to assess the risk and potential mechanisms of cardiovascular adverse events in patients treated with nilotinib or imatinib by conducting a systematic review, meta-analysis and integrative bioinformatics analysis.Materials and methods: Three databases were systematically searched for studies published from inception to May 29, 2022. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to search for modules of genes most associated with cardiotoxicity. Protein-protein interaction (PPI) network analysis was then performed to identify hub genes for the cardiotoxicity of nilotinib. Molecular docking was used to analyze the effects of rosuvastatin and aspirin on these targets.Results: Patients treated with nilotinib as first-line treatment were associated with a higher risk of CAE (OR = 3.43 [95% CI 2.77–4.25]), CAD (OR = 5.30 [95% CI 3.85–7.29]), ACS (OR 2.7 [95% CI 1.60–4.54]), CVA (OR 5.76 [95% CI 2.84–11.28]), PAOD (OR 5.57 [95% CI 3.26–9.50]) and arrhythmia (OR 2.34 [1.17,4.67]) than those treated with imatinib, while no significant difference was found in the risk of HF (OR 1.40 [95% CI 0.42–4.69]) between the two groups. Patients who were treated with more than 600 mg daily dosage of nilotinib or followed up for more than 5 years had a higher risk of ACS and CVA. IL6, CXCL8, CCL2, SOD2, NFKBIA, and BIRC3 were identified as the top 6 hub genes in the magenta module (human cardiomyocyte samples) and were mainly enriched in the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, lipid and atherosclerosis signaling pathway. TYROBP and CSF1R were identified as hub genes in the turquoise module (liver samples from Mus musculus). GSEA results showed that type II diabetes mellitus, B-cell receptor, apoptosis, insulin, natural killer cell mediated cytotoxicity,mTOR, chemokine, and T-cell receptor signaling pathways were related to the higher risk of atherosclerosis caused by nilotinib. Rosuvastatin can effectively bind to most of the hub targets and proteins enriched in the inflammatory pathways above.Conclusion: CML patients who start with nilotinib have a higher risk of CAE than those with imatinib. Atherosclerosis caused by the inflammatory response and glycolipid metabolism disorder is the key mechanism of nilotinib cardiotoxicity. Rosuvastatin may be an effective treatment for the cardiotoxicity of nilotinib.

Objective: We aimed to compare the efficacy, acceptability, and tolerability of vortioxetine in the treatment of Major Depressive Disorder (MDD) in adults.Method: We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Clinical Trials (CENTRAL), and www.ClinicalTrials.gov for randomized controlled trials that examined vortioxetine vs. placebo or other antidepressants for the treatment of MDD from database inception to August 30, 2021, using keywords Vortioxetine, Brintellix, Trintellix, LuAA21004, major depressive disorder, mood disorder, affective disorder, and MDD. We identified 789 publications after removing duplicates. After screening, 20 eligible randomized controlled trials were identified, of which 19 were included in the final meta-analysis. We included adults (aged 18 years and older) with a primary diagnosis of MDD. Two review authors independently selected the studies and extracted data. We extracted data on study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability, and tolerability. Analyses were performed using random-effects models, and outcomes were pooled as risk ratios (RRs) and standardized mean differences (SMDs).Results: In total, 20 studies (8,547 participants) met the inclusion criteria. Vortioxetine outperformed the placebo in efficacy outcomes, including response (RR 1.35, 95% CI 1.23–1.48; P < 0.001), remission (RR 1.33, 95% CI 1.17–1.52; P < 0.001), and cognitive function (SMD 0.34, 95% CI 0.16–0.52; P = 0.0003). Compared with the serotonin noradrenaline reuptake inhibitors (SNRIs), vortioxetine had better tolerability (RR 0.90, 95% CI 0.86–0.94; P < 0.001) but no significant difference in response (RR 0.91, 95%CI 0.82–1.00; P = 0.06) or remission (RR: 0.99, 95% CI 0.81–1.20, P = 0.88). Vortioxetine had no difference in response (RR 1.08, 95% CI 0.88–1.32; P = 0.46), remission (RR 1.00, 95% CI 0.41–2.44; P = 1.00) comparing with selective serotonin reuptake inhibitors (SSRIs).Conclusions: Vortioxetine is more advantageous over placebo in treating MDD among adults, but no significant difference compared to SNRIs and SSRIs in general.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42021278355, identifier: CRD42021278355.