BRAFV600E mutation is highly prevalent in patients with papillary thyroid carcinoma (PTC), and TERT promoter (TERTp) mutation is strongly associated with cancer‐related mortality. However, predictive power of the two mutations remains inconclusive. We aimed to verify the prognostic effects of both mutations to assess the value of mutation detection for risk stratification in terms of PTC prognosis and tumour invasion, to guide PTC diagnosis and treatment. We conducted a literature search in the MEDLINE (PubMed), EMBASE, Web of Science and CENTRAL (Cochrane library) databases, from inception to February 2020. Basic characteristics, prognoses and clinicopathological features were collected from the included studies for further analysis. Twelve studies involving 4184 PTC patients were enrolled in our analysis. In total, 2412 (57.6%) of the patients carried either BRAFV600E or TERTp mutation, and 290 (6.9%) patients had both mutations. TERTp mutation was more common in patients with BRAFV600E mutation (RR = 1.75 [95% CI 1.44‐2.13]). Patients with both mutations had a worse prognosis compared with those with a single mutation (vs BRAFV600E only: RR = 5.34 [4.20‐6.78] vs TERTp only: RR = 2.12 [1.41‐3.19]). TERTp mutation alone independently increased the risk of a poor prognosis (RR = 2.90 [1.93‐4.35]) in terms of mortality (RR = 15.09 [7.75‐29.37]), disease persistence (RR = 4.00 [2.03‐7.90]), recurrence (RR = 4.34 [4.20‐6.78]), lymph node metastasis (RR = 1.57 [1.24‐1.99]) and distant metastasis (RR = 2.94 [1.13‐7.65]). We found that PTC patients with BRAFV600E mutation were more likely to have TERTp mutation. TERTp mutation was an independent predictive factor for poor prognosis of PTC patients, but the predictive value of BRAFV600E mutation remains inconclusive. Patients with both mutations have remarkably higher risks of adverse outcomes compared with those with a single mutation. PTC patients could benefit from mutation detection for aiding risk stratification (BRAF + TERT+ > BRAF − TERT+ > BRAF + TERT−).

Purpose D3 lymphadenectomy for right colon cancer improves oncological outcomes. This meta-analysis aimed to compare operation data, histopathological characteristics, perioperative conditions, and long-term survival after D3 and D2 lymphadenectomy in right hemicolectomy. Methods We searched PubMed, Embase, and the Cochrane Library for relevant articles (up to March 31, 2020). Random-effects and fixed-effects meta-analysis models were used. Review Manager (RevMan) version 5.3 and Stata version 15.1 were used for pooled estimates. Results After screening 714 articles, 7 articles with a total of 1368 patients were eligible for inclusion. Compared with D2, D3 lymphadenectomy improves results in terms of blood loss (weighted mean difference [WMD] = −20.63, 95% confidence interval [CI] −28.19 to −13.16, P < .01), harvested lymph nodes (WMD = 8.86, 95% CI 7.74 to 9.98, P < .01), 3-year overall survival (OS) (hazard ratio [HR] = 2.03, 95% CI 1.20 to 3.43, P < .01), 5-year OS (HR = 2.22, 95% CI 1.15 to 4.30, P = .02), and 5-year disease-free survival (DFS) (HR = 2.16, 95% CI 1.19 to 3.90, P = .01). There was no significant difference regarding operation time, anastomosis leakage, wound infection, overall morbidity, postoperative hospital stay, mortality, length of dissected colon, and 3-year DFS ( P >= .05). Conclusions It is suggested in this review that D3 lymphadenectomy is superior to D2 lymphadenectomy in terms of blood loss, harvested lymph nodes, 3-year OS, 5-year OS, and 5-year DFS. The conclusion must be drawn with caution due to the limited number of included studies. Further RCTs are needed for stronger evidence.

BackgroundPapillary thyroid carcinoma (PTC) is the most common thyroid malignancy, but little is known regarding PTC metabolic phenotypes and the effects of mitochondrial activity on PTC progression. The great potential of mitochondria-targeting therapy in cancer treatment promoted us to use tool compounds from a family of Mito-Fu derivatives to investigate how the regulation of mitochondrial respiration affected tumor progression characteristics and molecular changes in PTC.MethodsMito-Fu L20, a representative of 12 synthetic derivatives, was chosen for mitochondrial inhibition experiments. Sample sections from PTC patients were collected and processed to explore potential molecular alterations in tumor lymph node metastasis (LNM). In vitro analyses were performed using human PTC cell lines (K1 and TPC-1), with the human normal thyroid follicular cell line (Nthy) as a control. K1 cells were injected into nude mice to generate an animal model. The mice were injected with normal saline or Mito-Fu L20 at 20 or 50 mg/kg every other day; their body weights and tumor volumes were also measured over time. To elucidate the resulting metabolic phenotype, we measured oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), cellular adenosine triphosphate (ATP) levels and reactive oxygen species (ROS) production, and mitochondrial membrane potential. Wound healing and Transwell assays, cell cycle assays, real-time fluorescence quantitative PCR, Western blotting, and immunohistochemical staining were performed to explore glycolysis-dominant metabolism in PTC.ResultsCyclin D1 and mitochondrial complex IV were detected in tumor samples from PTC patients with LNM. Mito-Fu L20 showed dose-independent and reversible modulation of mitochondrial respiration in PTC. In addition to mitochondrial dysfunction and early apoptosis, G1/S phase arrest. Notably, reversible mitochondrial inhibition yielded durable suppression of tumor proliferation, migration, and invasion via the PI3K/Akt/FoxO1/Cyclin D1 pathway. In vivo experiments demonstrated that Mito-Fu L20 has a good safety profile and specific restorative effect on mitochondrial activity in the liver. In addition, Mito-Fu L20 showed antitumor effects, alleviated tumor angiogenesis, and improved thyroid function.ConclusionReversible inhibition of ATP production and durable suppression of PTC growth indicates that the downregulation of mitochondrial function has a negative impact on tumor progression and LNM via the PI3K/Akt/FoxO1/Cyclin D1 pathway. The results provide new insights into the antitumor potential and clinical translation of mitochondrial inhibitors.

Knee osteoarthritis (KOA) is characterized by cartilage damage, and the associated pathogenesis is complex. The expression of dual specificity protein phosphatase 4 (DUSP4) is significantly decreased in osteoarthritis (OA); however, the specific role and mechanism underlying DUSP4 in OA are yet to be elucidated. ATDC5 cells were treated with lipopolysaccharide (LPS) to establish the cell injury model. The expression levels of DUSP4 were decreased in OA chondrocytes, demonstrated by reverse transcription-quantitative PCR and western blot analysis. Following overexpression of DUSP4 by cell transfection, Cell Counting Kit-8, ELISA, TUNEL and western blotting assays were used to detect the cell viability, oxidative stress, inflammation and apoptosis levels of LPS-induced ATDC5 cells. Overexpression of DUSP4 inhibited the activation of the MAPK signaling pathway, thereby reducing oxidative stress levels, inflammatory response and apoptosis in the OA cell model. The mechanisms underlying DUSP4 in OA were further explored following the addition of MAPK signaling pathway agonist, phorbol 12-myristate 13-acetate (PMA). The addition of PMA reversed the inhibitory effects of DUSP4 overexpression on oxidative stress, inflammatory response and apoptosis in cells. In summary, DUSP4 alleviated LPS-induced chondrocyte injury in KOA via the MAPK signaling pathway.

This study aimed to develop functional fruit wines using whole fruit, pulp, and peels from green bananas. The boiled banana homogenates were mixed with cane sugar before wine fermentation. Quality parameters, phenolic compounds, flavor components, and antioxidative properties of the green banana peel wine (GBPW), green banana pulp wine (GBMW), and whole banana wine (GBW) were determined. High-performance liquid chromatography was used to determine the phytochemical compounds in three wines, and the flavor components were further analyzed using headspace solid-phase microextraction combined with gas chromatography–mass spectrometry. The flavor components and in vitro antioxidant activities were, respectively, determined using the relative odor activity value and the orthogonal projections on latent structure discrimination analysis (OPLS-DA). In vitro antioxidative capacities for these wines were evaluated using antioxidant chemical assays and cell culture methods. The total phenolic and total tannin content of the GBPW, GBMW, and GBW showed reducing trends with increasing fermentation days, whereas the total flavonoid content of the wine samples exhibited downward trends. The antioxidant capacities of the three wine samples were higher than those of the raw fruit samples, except for the metal chelation rate (%). Additionally, the main flavor component in the wine samples was 3-methyl-1-butanol. Its percentages in the GBPW, GBMW, and GBW were 72.02%, 54.04%, and 76.49%, respectively. The OPLS-DA results indicated that the three wines presented significantly different antioxidant activities. The cell-culture-based antioxidant analysis showed that these wine samples had protective effects against the oxidative stress of the 3T3-L1 preadipocytes induced by hydrogen peroxide. This study provided a theoretical basis for defining the antioxidant characteristics of banana wines and expanding novel channels for using banana peels to develop nutraceuticals.

The majority of patients diagnosed with nasopharyngeal carcinoma (NPC) present with advanced-stage disease. The main treatment for these patients is concurrent chemoradiotherapy, which has various side effects. To improve the therapeutic effects and reduce the side effects of NPC chemoradiotherapy, we constructed a multifunctional folic acid (FA)-targeted magnetic nanocomposite codelivering tissue factor pathway inhibitor-2 (TFPI-2) and cisplatin (CDDP). This novel nanocomposite (FA-MNP/CDDP/TFPI-2) was obtained by amidation and electrostatic adsorption between FA-methoxypolyethylene glycol-polyethyleneimine (FA-MPEG-PEI) containing the TFPI-2 plasmid and magnetic nanoparticles modified by aldehyde sodium alginate loaded with CDDP. Transmission electron microscopy (TEM) images showed that the size of the individual magnetite particle core was approximately 11.5 nm. The structure and composition of the nanocomposites were identified and examined by 1 H nuclear magnetic resonance (NMR) spectroscopy and ultraviolet (UV) spectrophotometry. The fluorescence analysis, Prussian blue iron staining, magnetic resonance (MR) imaging and whole-body fluorescence imaging results demonstrated that FA-MNP/CDDP/TFPI-2 showed high gene transfection efficiency and could target tumor cells via folate receptor (FR)-mediated delivery. The codelivery analysis showed that the obtained FA-MNP/CDDP/TFPI-2 composite could cause significantly more apoptosis than treatment with CDDP or TFPI-2 alone. The results showed that the FA-MNP/CDDP/TFPI-2 composites were successfully synthesized and indicated to be a specific molecular target for the FR with significant inhibitory effects on the growth of HNE-1 cells.

Head and neck squamous cell carcinomas (HNSCCs) arising from different anatomical sites present with different incidences and characteristics, which requires a personalized treatment strategy. Despite the extensive research that has conducted on this malignancy, HNSCC still has a poor overall survival rate. Many attempts have been made to improve the outcomes, but one of the bottlenecks is thought to be the lack of an effective biomarker with high sensitivity and specificity. Extracellular vesicles (EVs) are secreted by various cells and participate in a great number of intercellular communications. Based on liquid biopsy, EV detection in several biofluids, such as blood, saliva, and urine, has been applied to identify the existence and progression of a variety of cancers. In HNSCC, tumor-derived EVs exhibit many functionalities by transporting diverse cargoes, which highlights their importance in tumor screening, the determination of multidisciplinary therapy, prediction of prognosis, and evaluation of therapeutic effects. This review illustrates the classification and formation of EV subtypes, the cargoes conveyed by these vesicles, and their respective functions in HNSCC cancer biology, and discloses their potential as biomarkers during the whole process of tumor diagnosis, treatment, and follow-up.

A novel ultrasonography-guided high intensity focused ultrasound (HIFU) system (FS-100; Force Electronics Co. Ltd, Chongqing, China) was developed for non-invasive thermal ablation of tumor. The proprietary therapy delivery system is an integration of the digital image progressing, automatic control and the high intensity focused ultrasound thermal ablation devices. The therapeutic ultrasound probe (φ = 240 mm) consists of eight circular HIFU transducers with a curved surface of a diameter of 60 mm. Dual focused beams generated from the probe were used in this system for thermal delivery. The probe has the maximal resonance frequency of 1 MHz, a maximal treatment depth of 160 mm and focal spot diameter of 3 mm. The maximal intensity at the focal spot is 10,000 W/cm 2 . The imaging and HIFU components are located on top of the device, therefore, the focused ultrasound beams can be delivered to the patient in a supine position. The motion, targeting and localization of the probe are controlled by a PMAC-PC motion controller and an 8-independent-axis mechanical device. The linear motion error of the probe localization is ≤ 0.1 mm. The ultrasonographic image information is used for treatment planning and therapeutic interventions, such as target definition and registration, visualization of the three-dimensional anatomy of desired target(s), automatic positioning the thermal beams on targets, controlling thermal delivery, and rapid evaluation of target response post-treatment. The preclinical experimental results will be presented. The safety, feasibility and effectiveness of this novel HIFU system will be tested.