Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3 Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth. The identified loss-of-function mutations in NFKBIA leading to protein truncation contributed to the altered NF-κB activity, which is critical for NPC tumorigenesis. In addition, somatic mutations were found in several cancer-relevant pathways, including cell cycle-phase transition, cell death, EBV infection, and viral carcinogenesis. These data provide an enhanced road map for understanding the molecular basis underlying NPC.

Mycotic aneurysm of the root of left subclavian artery associated with aortic coarctation discovered by echocardiography.

A 16-year-old girl was admitted with a 7-month history of recurrent fever, weight loss of 5 kg, and general poor health status. Blood culture was positive with Streptococcus viridans. Transthoracic echocardiography established an aneurysm of the root of left subclavian artery, associated with an aortic coarctation just before the origin of the left subclavian artery with a velocity of 4.8 cm/s. Three-dimensional echocardiography demonstrated the entire inner structure of the aneurysm. Computed tomography reconstruction confirmed the presence of aortic coarctation and mycotic aneurysm, it also revealed an aberrant right subclavian artery.

[Application of Echocardiography to Support Transapical Transcatheter Aortic Valve Implantation in Patients with Aortic Regurgitation].

OBJECTIVE: To explore the role of echocardiography in pre-procedural,peri-procedural and post-procedural stages of transapical transcatheter aortic valve implantation (TAVI) in patients with aortic regurgitation (AR). METHODS: 31 patients with pure/dominant AR at a high risk on surgery were enrolled in this study. The degree of their aortic regurgitation was evaluated before TAVI,as well as the related diameters of aortic root and the left ventricular systolic function measured by transthoracic echocardiography (TTE). TEE was used to reevaluate the valve pathology after general anesthesia. TEE in combination with fluoroscopy provided accurate position of the prosthetic valve for implantation. TEE was also used to monitor complications and to evaluate immediate post-procedure paravalvular regurgitation. The post TAVI follow-up included valve heamodynamic status,complications,left ventricular systolic function and left ventricular mass index (LVMI) measured by TEE. RESULTS: Transapical TAVI was successful in 29 of the 31 patients: 23 experienced no or little paravalvular regurgitation; 6 had mild paravalvular regurgitation. The left ventricular end-diastolic diameter (LVDd) and left ventricular mass index (LVMI) of the patients decreased significantly one week after TAVI,which progressed until one month later ( P<0.05) . The left ventricular ejection (EF) of the patients also decreased one week after TAVI ( P<0.05) ,but it resumed to the pre-procedural level one month later. CONCLUSION: Transapical TAVI is a potentially safe and effective therapy for patients with pure/dominant AR at a high risk on open-heart surgery. Echocardiography plays an important role in pre-procedural evaluation,peri-procedural monitoring and post-procedural follow-up in TAVI.

Epigenetic Silencing of Tumor Suppressor lncRNA NKILA: Implication on NF-κB Signaling in Non-Hodgkin's Lymphoma.

The long non-coding RNA (lncRNA) NKILA, localized to 20q13.31, is a negative regulator of NF-κB signaling implicated in carcinogenesis. As a CpG island is embedded in the promoter region of NKILA, it is hypothesized as a tumor suppressor lncRNA silenced by promoter DNA methylation in non-Hodgkin's lymphoma (NHL). By pyrosequencing-verified methylation-specific PCR, NKILA methylation was detected in 1/10 (10%) NHL cell lines, but not in normal peripheral blood buffy coats or tonsils. NKILA methylation correlated with the repression of NKILA in cell lines. Hypomethylation treatment with 5-Aza-2'-deoxycytidine resulted in promoter demethylation and the re-expression of NKILA. In 102 NHL primary samples, NKILA was methylated in 29 (51.79%) diffuse large B-cell lymphoma (DLBCL) and 4 (20%) peripheral T-cell lymphoma cases, but unmethylated in all 26 mantle cell lymphoma cases. Mechanistically, the knockdown of NKILA resulted in promoting IkBα phosphorylation, associated with nucleus translocation of total p65 and phosphorylated p65 in SU-DHL-1 cells, hence constitutive NF-κB activation. Functionally, the knockdown of NKILA in SU-DHL-1 cells led to decreased cell death and increased cellular proliferation. Collectively, NKILA was a tumor suppressor lncRNA frequently hypermethylated in DLBCL. Promoter DNA methylation-mediated NKILA silencing resulted in increased cellular proliferation and decreased cell death via the repression of NF-κB signaling in NHL.

Cylindromatosis Lysine 63 Deubiquitinase (CYLD) Regulates NF-kB Signaling Pathway and Modulates Fibroblast and Endothelial Cells Recruitment in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the nasopharynx. Cylindromatosis lysine 63 deubiquitinase (CYLD), a NF-kB inhibitor, was reported as one of the top mutated candidate genes in NPC. NF-kB is an inducible transcription factor, contributing to cancer via regulating inflammation, angiogenesis, cell proliferation, and metastasis. In this study, the impact of CYLD on regulating the NF-kB signaling pathway and its contribution to NPC development was studied using in vitro and in vivo functional assays, together with single cell RNA sequencing to understand the NPC tumor microenvironment. CYLD was downregulated in NPC clinical specimens and multiple cell lines. Functional assays revealed CYLD inhibits NPC cell proliferation and migration in vitro and suppresses NPC tumorigenicity and metastasis in vivo by negatively regulating the NF-kB signaling pathway. Additionally, CYLD was able to inhibit fibroblast and endothelial stromal cell infiltration into the NPC tumor microenvironment. These findings suggest that CYLD inhibits NPC development and provides strong evidence supporting a role for CYLD inhibiting fibroblast and endothelial stromal cell infiltration into NPC via suppressing the NF-kB pathway.

Changes in left ventricular function in patients with aortic regurgitation 12 months after transapical transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is an established treatment for high surgical risk aortic stenosis patients; in recent years, it has also been used in patients with pure/dominant aortic regurgitation (AR). This study aimed to determine the impact of transapical TAVI on left ventricle myocardial mechanics in AR patients. Thirty AR patients (70% men; mean age, 72.8 ± 4.3 years) were enrolled. Conventional echocardiography was performed on all patients before and 12 months after TAVI. Three-dimensional speckle tracking was accomplished in 20 AR patients for the evaluation of global longitudinal strain, global circumferential strain, twist, torsion, apical rotation and basal rotation. Preoperative left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), global circumferential strain (GCS), twist, torsion and apical rotation were impaired in AR patients compared with controls. Mean left ventricular (LV) end-diastolic diameter (from 62.9 ± 7.3 to 52.0 ± 6.8 mm, p < 0.001), LV end-diastolic volume (from 199.4 ± 55.0 to 130.1 ± 48.9 mL, p < 0.001), and LV mass index (179.8 ± 52.2-134.4 ± 42.5 g/m2, p = 0.001) decreased 12 months after TAVI. Interestingly, GLS (from - 17.2 ± 3.2 to - 18.9 ± 3.7, p = 0.007) and GCS (from - 23.9 ± 4.9 to - 25.7 ± 5.0, p = 0.008) improved significantly, but LVEF did not significantly improve. In terms of the rotational mechanics, twist, rotation and basal rotation remained almost unchanged, whereas apical rotation (from 7.4 ± 4.0 to 5.5 ± 3.9, p = 0.009) was significantly impaired after transapical TAVI. Our results indicate that LV function was improved in terms of myocardial deformation but worsened in terms of apical rotation 12 months after TAVI in AR patients. Three-dimensional speckle tracking echocardiography appears to be a sensitive method for detecting subtle cardiac remodeling after TAVI.

Cardiac inflammatory myofibroblastic tumor in interventricular septum: A rare case report.

RATIONALE: Cardiac inflammatory myofibroblastic tumor (IMT) is a rare primary cardiac tumor which is currently considered as a low-grade neoplasm. The tumor has a predilection in infants and adolescents and primarily occurs as an endocardial-based cavitary mass. However, cardiac IMT that only involves the interventricular septum in middle-aged adults is extremely rarely reported. Considering its infrequency, we report a rare clinical case, with the aim of sharing our experience during the diagnostic procedures. PATIENT CONCERNS: A 45-year-old, previously healthy female, with no medical history was admitted to the outpatient clinic due to the identification of an abnormal radiographic finding during a routine health examination. DIAGNOSIS: Transthoracic echocardiography (TTE) revealed a 3.5 cm × 4.0 cm × 4.5 cm heterogeneous mass in the interventricular septum. Color Doppler echocardiography detected sparse blood flow signals inside the mass. Magnetic resonance imaging (MRI) confirmed a hyperintense T2-weighted, isointense T1-weighted mass. Three-dimensional (3D) TTE demonstrated a spherical mass in the middle part of the interventricular septum. Postoperative histopathological examinations revealed a mesenchymal tumor composed of scattered spindle myofibroblasts with a myxoid atypia, associated with infiltration of lymphocytes and plasma cells. INTERVENTIONS: Complete tumor resection was successfully performed via median sternotomy under general anesthesia. OUTCOMES: After surgery, the patient recovered successfully. The patient was in good general health without any clinical symptoms. The echocardiographic examination at the 12-month follow-up period revealed normal function of the heart, and there was no evidence of tumor recurrence. LESSONS: To our knowledge, cardiac IMT only the involving interventricular septum in a middle-aged adult has never been previously reported before. Echocardiography plays a critical role in establishing the primary diagnosis of cardiac IMT and evaluating regular follow-up examinations. Complete surgical resection of the mass is considered the first-line treatment despite the absence of symptoms.

Functional Characterization of BoaMYB51s as Central Regulators of Indole Glucosinolate Biosynthesis in Brassica oleracea var. alboglabra Bailey.

R2R3-MYB transcription factor MYB51 is known to control indole glucosinolate (indole GSL) biosynthesis in Arabidopsis. Here, two copies of BoaMYB51 have been isolated in Chinese kale (Brassica oleracea var. alboglabra Bailey), designated BoaMYB51.1 and BoaMYB51.2, which exhibit overlapping but distinct expression levels among different organs and respond to signaling molecules in a similar pattern. It has been demonstrated a structural and functional conservation between BoaMYB51s and AtMYB51 by phylogenetic analysis, complementation studies and transient expression assay. To further investigate the transcriptional mechanism, we identified the transcriptional activation domain (TAD) and putative interacting proteins of BoaMYB51s by means of yeast (Saccharomyces cerevisiae) two hybrid. Using tobacco (Nicotiana benthamiana) transient expression assay, we confirmed that the carboxy-end is required for transcriptional activation activity of BoaMYB51s. In addition, several BoaMYB51-interacting proteins have been identified by yeast two-hybrid screening. These results provide important insights into the molecular mechanisms by which MYB51 transcriptionally regulates indole GSL biosynthesis.

Influence of pre-harvest red light irradiation on main phytochemicals and antioxidant activity of Chinese kale sprouts.

The effects of pre-harvest red light irradiation on main healthy phytochemicals as well as antioxidant activity of Chinese kale sprouts during postharvest storage were investigated. 6-day-old sprouts were treated by red light for 24h before harvest and sampled for further analysis of nutritional quality on the first, second and third day after harvest. The results indicated that red light exposure notably postponed the degradation of aliphatic, indole, and total glucosinolates during postharvest storage. The vitamin C level was remarkably higher in red light treated sprouts on the first and second day after harvest when compared with the control. In addition, red light treatment also enhanced the accumulation of total phenolics and maintained higher level of antioxidant activity than the control. All above results suggested that pre-harvest red light treatment might provide a new strategy to maintain the nutritive value of Chinese kale sprouts during postharvest storage.

A comparison of anterior cervical discectomy and fusion combined with cervical disc arthroplasty and cervical disc arthroplasty for the treatment of skip-level cervical degenerative disc disease: A retrospective study.

Anterior cervical discectomy and fusion (ACDF) has been widely performed for the treatment of multilevel cervical degenerative disc disease (CDDD). In recent decades, cervical disc arthroplasty (CDA) and hybrid surgery (HS) have been developed to overcome the shortcomings of ACDF. Controversy still remains with regard to the optimal surgical procedure for skip-level CDDD.A total of 55 patients who received surgical treatment for skip-level CDDD in our department were reviewed. The patients were divided into the HS group (n = 29) and the CDA group (n = 26). The collected data included Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), and Visual Analog Scale (VAS) scores, and cervical lordosis (CL), range of motion (ROM), and intervertebral disc height (IDH). Radiological changes at the intermediate segment (IS) were also collected. All data were collected preoperatively and at routine postoperative intervals of 1 week and 3, 6, and 12 months and at the last follow-up period.Compared with preoperative values, mean JOA, NDI, and VAS scores significantly improved after surgery in both the HS and CDA groups (P < .05). However, there were no significant differences between the groups (P > .05). The HS group had better CL recovery than the CDA group after surgery (P < .05). There was no significant difference in the ROM of C2-C7 between the 2 groups (P > .05). A significant difference in the ROM of the IS was found at the last follow-up between the 2 groups (P < .05). At the last-follow-up, 4 discs (14.29%) in the CDA group and 6 discs (19.36%) in the HS group had adjacent segment degeneration (ASD) without symptoms.Both HS and CDA might be considered safe and effective surgical strategies for the treatment of skip-level CDDD. Although the clinical outcomes were similar in the 2 groups, CDA altered the ROM of the IS to a lesser degree.

Cervical disc arthroplasty for the treatment of adjacent segment disease: A systematic review of clinical evidence.

The safety and efficacy of cervical disc arthroplasty (CDA) performed adjacent to previous fusion for the treatment of adjacent segment disease (ASD) remains unknown. This systematic review summarizes clinical evidence on the outcomes of CDA performed adjacent to previous cervical fusion. A systematic search of PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase for literature published through March 2017 was conducted. All the studies on CDA for the treatment of ASD after cervical fusion surgery were included. Two independent reviewers searched and assessed the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). A total of 5 studies were identified. The overall quality of evidence was low. All included studies demonstrated that clinical outcomes reflected by several assessment scales improved after arthroplasty. Cervical lordosis range of motion (ROM) after arthroplasty remained and was even enhanced postoperatively. The rate of complications and subsequent surgeries was low. There is a dearth of information regarding the outcomes of CDA for the treatment of ASD in the literature. In general, CDA may be a safe and effective surgical procedure to treat ASD, but this conclusion needs to be confirmed by future long-term, prospective clinical trials.

Effects of light quality on main health-promoting compounds and antioxidant capacity of Chinese kale sprouts.

The effects of different light qualities, including white, red and blue lights, on main health-promoting compounds and antioxidant capacity of Chinese kale sprouts were investigated using light-emitting diodes (LEDs) as a light source. Our results showed that blue light treatment significantly decreased the content of gluconapin, the primary compound for bitter flavor in shoots, while increased the glucoraphanin content in roots. Moreover, the maximum content of vitamin C was detected in the white-light grown sprouts and the highest levels of total phenolic and anthocyanins, as well as the strongest antioxidant capacity were observed in blue-light grown sprouts. Taken together, the application of a colorful light source is a good practice for improvement of the consumers' acceptance and the nutritional phtyochemicals of Chinese kale sprouts.