Knowledge, attitudes, barriers and practices concerning cancer therapy-associated oral mucositis amongst oncology nurses: A mixed methods systematic review.

Objectives: To evaluate oncology nurses' knowledge, attitudes, barriers and practices regarding the prevention and management of cancer therapy-associated oral mucositis. Methods: A systematic review was conducted by â€‹mixed-methods; searches were conducted in PubMed, EMBASE, Medline, CINAHL, Cochrane Library and Web of Science databases. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed for the systematic review. Searched relevant literature â€‹published in English between January 2000 and December 2023. The Mixed Methods Appraisal Tool was used to evaluate the quality of the studies. Results: A total of 15 studies were included: 10 cross-sectional studies, 4 non-randomized controlled trials, and one qualitative study. This review provides an overview of the studies: nurses had limited knowledge of cancer therapy-associated oral mucositis; generally positive attitudes towards oral care; there is a slight difference in oral care practices. The main barriers of nurses' prevention and management of cancer therapy-associated oral mucositis were lack of time, lack of knowledge, and lack of staff. Conclusions: Our results highlight the importance of training for oncology nurses regarding the management of cancer therapy-associated oral mucositis. It is suggested that oncology nurses should focus on strengthening and continuing education in oral care, adopting evidence-based practice and evaluation systems, implementing institution-specific written standards for oral care protocols, and promoting multidisciplinary team cooperation.

Risk factors for postoperative cerebrospinal fluid leakage after transsphenoidal surgery for pituitary adenoma: a meta-analysis and systematic review.

OBJECTIVE: Postoperative cerebrospinal fluid (CSF) leakage represents a challenge even for experienced pituitary surgeons. We aimed to quantitatively synthesize data from studies regarding the risk factors for postoperative CSF leakage after transsphenoidal surgery (TSS) for pituitary adenoma (PA). METHODS: PubMed, Web of Science, The Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database were searched for case-control and cohort studies, focusing on the risk factors associated with postoperative CSF leakage after TSS for PA. Pooled odds ratios (ORs) and 95% confidence intervals were calculated to determine the risk factors. RESULTS: A total of 34 case-control and cohort studies involving a total of 9,144 patients with PA were included in this systematic review. The overall rate of postoperative CSF leakage after TSS for PA was 5.6%. Tumor size, adenoma consistency, revision surgery, and intraoperative CSF leakage were independent risk factors for postoperative CSF leakage (ORs, 3.18-6.33). By contrast, the endoscopic approach showed a slight protective benefit compared with the microscopic approach in TSS (OR, 0.69). CONCLUSIONS: This review provides a comprehensive overview of the quality of the evidence base, informing clinical staff of the importance of screening risk factors for postoperative CSF leakage after TSS for PA. More attention should be paid to PA patients at high risk for CSF leakage after TSS to reduce complications and improve prognosis.

Retraction Note to: Ultrasound Elastography supplement assessing nodal status of magnetic resonance imaging staged cervical N0 patients with nasopharyngeal carcinoma.

The Editors have retracted this article [1] because figure 2 has been substantially duplicated from a previously published article by Chen B et al., 2018 [2]. There is also significant and uncited overlap in the patient population between the two articles resulting in concerns relating to the scientific validity and novelty of the data.

Ultrasound Elastography supplement assessing nodal status of magnetic resonance imaging staged cervical N0 patients with nasopharyngeal carcinoma.

BACKGROUND: To determine whether ultrasound elastography can distinguish reactive or metastatic small lymph nodes (sLN) of magnetic resonance imaging (MRI) staged cervical N0 patients with nasopharyngeal carcinoma (NPC). METHODS: A pilot study was performed involving the diagnostic performances of conventional high-frequency ultrasound (CHFU) and/or shear wave elastography (SWE) for predicting metastases in sLN of MRI-staged N0 NPC patients with reference to the histologically-proven ultrasound guided core needle biopsy (US-CNB). The diagnosis of CHFU was based on the superficial lymph node ultrasonic criteria with the five-point-scale (FPS). The mean (Emean), minimum (Emin) and maximum (Emax) of the elasticity indices were measured by SWE at the stiffest part of the sLN in kilopascal. Diagnostic performances were analyzed using a receiver operating curve (ROC) on a per-node basis. The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform ( http://www.researchdata.org.cn ), with the approval RDD number as RDDA2017000447. RESULTS: All 113 cervical sLN of 49 MRI-staged cervical N0 NPC patients underwent evaluation of CHFU and SWE; 38 sLN (FPS < 2) were regarded as benign, which were excluded from subsequent analysis due to none biopsy-proven. And 75 indeterminate sLN (FPS ≥ 2) were referred to US-CNB and revealed 15 (20%) metastases. All SWE elastic indices were significantly higher in malignant sLNs than in benign sLNs (p < 0.05). Moreover, Emax exhibited the highest diagnostic value (AUC:0.733 ± 0.067, p = 0.005) with excellent measurement reproducibility (ICC: 0.786; 95%CI: 0.684, 0.864). CHFU plus SWE was superior to CHFU or SWE alone for predicting metastases in sLN of MRI-staged N0 patients with NPC (p < 0.001). CONCLUSIONS: CHFU plus SWE is an optional non-invasive modality to supplement MRI in assessing cervical nodal status of patients with NPC.

Role of TRIM33 in Wnt signaling during mesendoderm differentiation.

Tripartite motif 33 (TRIM33), a member of the transcription intermediate factor 1 (TIF1) family of transcription cofactors, mediates transforming growth factor-beta (TGF-ß) signaling through its PHD-Bromo cassette in mesendoderm differentiation during early mouse embryonic development. However, the role of the TRIM33 RING domain in embryonic differentiation is less clear. Here, we report that TRIM33 mediates Wnt signaling by directly regulating the expression of a specific subset of Wnt target genes, and this action is independent of its RING domain. We show that TRIM33 interacts with ß-catenin, a central player in Wnt signaling in mouse embryonic stem cells (mESCs). In contrast to previous reports in cancer cell lines, the RING domain does not appear to function as the E3 ligase for ß-catenin, since neither knockout nor overexpression of TRIM33 had an effect on ß-catenin protein levels in mESCs. Furthermore, we show that although TRIM33 seems to be dispensable for Wnt signaling through a reporter assay, loss of TRIM33 significantly impairs the expression of a subset of Wnt target genes, including Mixl1, in a Wnt signaling-dependent manner. Together, our results indicate that TRIM33 regulates Wnt signaling independent of the E3 ligase activity of its RING domain for ß-catenin in mESCs.

A novel VHLα isoform inhibits Warburg effect via modulation of PKM splicing.

Von Hippel-Lindau (VHL) is the most frequently mutated gene in clear cell renal carcinoma. Here, we identified a novel translational variant of VHL, termed VHLα, initiated from an alternative translational start site upstream and in frame with the ATG start codon. We showed that VHLα interacts with and regulates heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), which consequently modulates pyruvate kinase transcript splicing and reprograms cellular glucose metabolism. Our study demonstrated that a novel VHL isoform may function as a tumor suppressor through inhibiting the Warburg effect.

Flavokawain A inhibits Cytochrome P450 in in vitro metabolic and inhibitory investigations.

ETHNOPHARMACOLOGICAL RELEVANCE: Flavokawain A, the major chalcone in kava extracts, was served as beverages for informal social occasions and traditional ceremonials in most South Pacific islands. It exhibited strong antiproliferative and apoptotic effects against human prostate and urinary bladder cancer cells. AIM OF THE STUDY: The current study was purposed to investigate the interaction between Flavokawain A and Cytochrome P450, including the inhibitory effects of Flavokawain A on predominant CYP450 isotypes and further clarified the inhibitory mechanism of FKA on CYP450 enzymes. Besides, study about identifying the key CYP450 isotypes responsible for the metabolism of FKA was also performed. MATERIALS AND METHODS: In this study, probe-based assays with rat liver microsome system were used to characterize the inhibitory effects of FKA. Molecular docking study was performed to further explore the binding site of FKA on CYP450 isoforms. In addition, chemical inhibition experiments using specific inhibitors (a-naphthoflavone, quinidine, sulfamethoxazde, ketoconazole, omeprazole) were performed to clarify the individual CYP450 isoform that are responsible for the metabolism of FKA. RESULTS: FKA showed significant inhibition on CYP1A2, CYP2D1, CYP2C6 and CYP3A2 activities with IC50 values of 102.23, 20.39, 69.95, 60.22µmol/L, respectively. The inhibition model was competitive, mixed-inhibition, uncompetitive, and noncompetitive for CYP1A2, CYP2D1, CYP2C6 and CYP3A2 enzymes. Molecular docking study indicated the ligand-binding conformation of FKA in the active site of CYP450 isoforms. The chemical inhibition experiments showed that the metabolic clearance rate of Flavokawain A decreased to 19.84%, 50.38%, and 67.02% of the control in the presence of ketoconazole, sulfamethoxazde and a-naphthoflavone. CONCLUSION: The study showed that Flavokawain A has varying inhibitory effect on CYP450 enzymes and CYP3A2 was the principal CYP isoform contributing to the metabolism of Flavokawain A. Besides, CYP2C6 and CYP1A2 isoforms also play important roles in the metabolism of FKA. Our results provided a basis for better understanding the biotransformation of FKA and prediction of drug-drug interaction of FKA.

The VHL short variant involves in protein quality control.

The von Hippel-Lindau (VHL) is the most important and frequently mutated gene in human clear cell renal cell carcinoma (ccRCC). In contrast to its long counterpart, the internal translational variant of VHL protein (VHLs) is evolutionarily conserved. Herein we present evidence that VHLs associates with ribosome complex via interaction with the large subunit 6 (RPL6). Manipulation of VHLs expression significantly alters protein synthesis, cell size and mitochondrial mass. VHLs deficiency leads to remarkable sensitivity to drug treatments eliciting nascent protein mis-folding and translational errors. The ubiquitination of nascent peptides are dramatically increased upon the ectopic over-expression of VHLs, which simultaneously co-localizes with proteasome and thus may facilitate the ubiquitin-proteasome mediated degradation. In summary, VHLs contributes to protein quality control in addition to its canonical function in maintaining homeostasis of hypoxia-induced factors alpha subunit (HIFα) in response to environmental oxygen supply.