Multidimensional Criteria for Virtual Screening of PqsR Inhibitors Based on Pharmacophore, Docking, and Molecular Dynamics.

Pseudomonas aeruginosa is a clinically challenging pathogen due to its high resistance to antibiotics. Quorum sensing inhibitors (QSIs) have been proposed as a promising strategy to overcome this resistance by interfering with the bacterial communication system. Among the potential targets of QSIs, PqsR is a key regulator of quorum sensing in Pseudomonas aeruginosa. However, the current research on PqsR inhibitors is limited by the lack of diversity in the chemical structures and the screening methods. Therefore, this study aims to develop a multidimensional screening model for PqsR inhibitors based on both ligand- and receptor-based approaches. First, a pharmacophore model was constructed from a training set of PqsR inhibitors to identify the essential features and spatial arrangement for the activity. Then, molecular docking and dynamics simulations were performed to explore the core interactions between PqsR inhibitors and their receptor. The results indicate that an effective PqsR inhibitor should possess two aromatic rings, one hydrogen bond acceptor, and two hydrophobic groups and should form strong interactions with the following four amino acid residues: TYR_258, ILE_236, LEU_208, and GLN_194. Moreover, the docking score and the binding free energy should be lower than -8 kcal/mol and -40 kcal/mol, respectively. Finally, the validity of the multidimensional screening model was confirmed by a test set of PqsR inhibitors, which showed a higher accuracy than the existing screening methods based on single characteristics. This multidimensional screening model would be a useful tool for the discovery and optimization of PqsR inhibitors in the future.

Elevated expression of TUBA1C in breast cancer predicts poor prognosis.

α1C-tubulin (TUBA1C) is a member of the α-tubulin family and has served as a potential biomarker in a variety of cancers in many studies. In this study, the gene expression profile of TUBA1C in The Cancer Genome Atlas (TCGA) was extracted for analysis, and the prognostic value of TUBA1C in breast cancer was comprehensively evaluated. The Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression analysis were performed to confirm the correlations between TUBA1C expression and the clinical characteristics of breast cancer patients. The effect of TUBA1C expression on the survival of breast cancer patients was assessed by Kaplan-Meier curve, Cox regression analysis, and the Kaplan-Meier plotter (an online database). The TCGA data set was used for the Gene Set Enrichment Analysis (GSEA). The results confirmed that high TUBA1C expression in breast cancer was closely correlated with survival time, survival status, and tumor size. In addition, elevated TUBA1C expression can predict poor overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Univariate and multivariate analyses (Cox regression analyses) confirmed that TUBA1C was an independent prognostic factor for the OS of breast cancer patients. The GSEA identified that the high TUBA1C expression phenotype was differentially enriched in cell cycle, basal transcription factor, P53 signaling pathway, pathways in cancer, TOLL-like receptor signaling pathway, and NOD-like receptor signaling pathway. In summary, high messenger RNA (mRNA) expression of TUBA1C is an independent risk factor for poor prognosis of breast cancer.

Endogenous H2O2 Self-Replenishment and Sustainable Cascades Enhance the Efficacy of Sonodynamic Therapy.

Purpose: Sonodynamic therapy (SDT), with its high tissue penetration and noninvasive advantages, represents an emerging approach to eradicating solid tumors. However, the outcomes of SDT are typically hampered by the low oxygen content and immunosuppression in the tumor microenvironment (TME). Accordingly, we constructed a cascade nanoplatform to regulate the TME and improve the anti-tumor efficiency of SDT. Methods: In this study, we rationally design cascade nanoplatform by incorporating immunostimulant hyaluronic acid (HA) and sonosensitizer chlorin e6 (Ce6) on the polydopamine nanocarrier that is pre-doped with platinum nanozymes (designated Ce6/Pt@PDA-HA, PPCH). Results: The cascade reactions of PPCH are evidenced by the results that HA exhibits reversing immunosuppressive that converts M2 macrophages into M1 macrophages in situ, while producing H2O2, and then platinum nanozymes further catalyze the H2O2 to produce O2, and O2 produces abundant singlet oxygen (1O2) under the action of Ce6 and low-intensity focused ultrasound (LIFU), resulting in a domino effect and further amplifying the efficacy of SDT. Due to its pH responsiveness and mitochondrial targeting, PPCH effectively accumulates in tumor cells. Under LIFU irradiation, PPCH effectively reverses immunosuppression, alleviates hypoxia in the TME, enhances reactive oxygen species (ROS) generation, and enhances SDT efficacy for eliminating tumor cells in vivo and in vitro. Meanwhile, an in vivo dual-modal imaging including fluorescence and photoacoustic imaging achieves precise tumor diagnosis. Conclusion: This cascade nanoplatform will provide a promising strategy for enhancing SDT eradication against tumors by modulating immunosuppression and relieving hypoxia.

Nomogram prediction for cervical lymph node metastasis in multifocal papillary thyroid microcarcinoma.

Aim: Accurate preoperative prediction of cervical lymph node metastasis (LNM) in patients with mPTMC provides a basis for surgical decision making and the extent of tumor resection. This study aimed to develop and validate an ultrasound radiomics nomogram for the preoperative assessment of LN status. Methods: A total of 450 patients pathologically diagnosed with mPTMC were enrolled, including 348 patients in the modeling group and 102 patients in the validation group. Univariate and multivariate logistic regression analyses were performed on the basic information, ultrasound characteristics, and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) scores of the patients in the modeling group to identify independent risk factors for LNM in mPTMC and to construct a logistic regression equation and nomogram to predict the risk of LNM. The validation group data were used to evaluate the predictive performance of the nomogram. Results: Male sex, age <40 years, a single lesion with a maximum diameter >0.5 cm, capsular invasion, a maximum ACR score >9 points, and a total ACR score >19 points were independent risk factors for the development of cervical LNM in mPTMC. Both the area under the curve (AUC) and concordance index (C-index) of the prediction model constructed from the above six factors were 0.838. The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, decision curve analysis (DCA) demonstrated a significantly greater net benefit of the model. The external validation demonstrated the reliability of the prediction nomogram. Conclusions: The presented radiomics nomogram, which is based on ACR TI-RADS scores, shows favorable predictive value for the preoperative assessment of LNs in patients with mPTMC. These findings may provide a basis for surgical decision making and the extent of tumor resection.

Recent advances in sonodynamic immunotherapy.

Tumor immunotherapy has become an important means of tumor therapy by enhancing the immune response and triggering the activation of immune cells. However, currently, only a small number of patients respond to immunotherapy alone, and patients may experience immune-related adverse events (irAEs) during the course of treatment. Sonodynamic therapy (SDT) can produce cytotoxic substances to tumor tissue, induce apoptosis and enhance immunity. SDT combined with immunotherapy is considered a promising strategy for cancer treatment. In this mini review, we summarize the role of SDT in immunotherapy in recent years, including the application of SDT-triggered immunotherapy and the combination of SDT and immunotherapy.

Responsive Accumulation of Nanohybrids to Boost NIR-Phototheranostics for Specific Tumor Imaging and Glutathione Depletion-Enhanced Synergistic Therapy.

Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH-responsive i-motif DNA-mediated strategy to tailor the programmable behaviors of erbium-based rare-earth nanoparticles (ErNPs) decorated copper doped metal-organic framework (CPM) nanohybrids (ECPM) under physiological conditions is reported. Within the acidic tumor microenvironment, the i-motif DNA strands are able to form quadruplex structures, resulting in the assembly of nanohybrids and selective tumor accumulation, which further amplify the ErNPs downconversion emission (1550 nm) signal for imaging. Meanwhile, the ECPM matrix acts as a near-infrared (NIR) photon-activated reactive oxygen species (ROS) amplifier through the singlet oxygen generation of the matrix in combination with its ability of intracellular glutathione depletion upon irradiation. In short, this work displays a classical example of engineering of nanoparticles, which will manifest the importance of developing nanohybrids with structural programmability in biomedical applications.

Construction of immune cell infiltration protein network based on clinical low grade glioma cases.

Many researchers have studied low-grade glioma and the immune microenvironment have been studied by many researchers. Recent studies suggest that macrophages and dendritic cells trigger part of the local immune dysregulation in the tumor microenvironment, and they have been polarized into a mixed pro-inflammatory and immunosuppressive phenotype. It is suggested that the degree of immune infiltration is related to the survival, therapeutic effect, and prognosis of patients. This opens up new avenues for cancer treatment. On the basis of immune infiltration degree, a protein interaction network (PIN) and a prognosis model were established, and we chose the top 20 pathways from enrichment analysis to provide potential targets for glioma clinical treatment.

Chelator Iminodisuccinic Acid Regulates Reactive Oxygen Species Accumulation and Improves Maize (Zea mays L.) Seed Germination under Pb Stress.

To explore the effects of iminodisuccinic acid (a chelating agent) on maize (Zea mays L.) seed germination under lead (Pb) stress, we comparatively analyzed the effects of applying different concentrations of iminodisuccinic acid (0, 5, 20, and 100 mmol·dm-3) and combined an addition of exogenous substances regulating reactive oxygen species production on maize seed germination, seedling growth, H2O2 content, NADPH oxidase activity, and antioxidant enzyme activities under Pb-stressed and Pb-free conditions. Iminodisuccinic acid (100 mmol·dm-3) significantly delayed seed germination under normal germination conditions and alleviated the inhibitory effects of Pb stress (20 mmol·dm-3) on seed germination. Under normal conditions (without Pb stress), the iminodisuccinic acid-induced inhibition of seed germination was enhanced by treatment with dimethylthiourea (a specific scavenger of reactive oxygen species) or diphenyleneiodonium chloride (a specific inhibitor of NADPH oxidase), but diminished by treatment with H2O2, CaCl2, diethyldithiocarbamic acid (a specific inhibitor of superoxide dismutase), or aminotriazole (a specific inhibitor of catalase). Under Pb stress, iminodisuccinic acid partially eliminated the excessive H2O2 accumulation, improved superoxide dismutase and catalase activity, and weakened the high NADPH oxidase activity. In addition, Ca2+ chelation may be essential for maintaining the reactive oxygen species' balance and improving seed germination and seedling growth by iminodisuccinic acid supplementation in maize under Pb stress. The proposed iminodisuccinic acid supplementation-based method improved maize seed germination in Pb-polluted soil.

A bimodal type of AgPd Plasmonic Blackbody Nanozyme with boosted catalytic efficacy and synergized photothermal therapy for efficacious tumor treatment in the second biological window.

Nanozymes are promising for precise cancer treatment, but are typically limited in terms of the low catalytic efficiency and the complexity in tumor microenvironment (TME). Herein, we describe a bimodal type of AgPd plasmonic blackbody (AgPd PB) nanozyme of compact sizes (< 30 nm), which presents not only boosted enzyme efficacy but also efficient photothermal therapy (PTT) for synergized therapy through tissue-penetrating light in the second biological window (1000-1700 nm). The synthesized hyperbranched AgPd PB nanozymes possess intense and broadband localized surface plasmonic resonance absorption of 400-1300 nm, entailing prominent photothermal efficiency (η = 45.1% at 1064 nm) for PTT. Importantly, PTT was found to significantly boost the nanozyme efficacy of both catalase (CAT) and peroxidase (POD) processes, which correspondingly decompose H2O2 to into O2 to relieve tumor hypoxia, and activate H2O2 to generate oxidative •OH radical. While the generated •OH was found to be able to minimize heat shock proteins (HSPs), which plays a vital role to counterbalance PTT effect both in vitro and in vivo. As compared to control ground without treatment, the synergized nanozyme and PTT activities resulted in about 7-fold reduction of tumor volume, thus elevating the survival rate from 0 to 80% at 30 days posttreatment. Besides the synergistic therapy, the AgPd PB nanozyme were shown to own fluorescence, computed tomography (CT), and photoacoustic (PA) imaging abilities, thus having implications for uses in imaging-guided precise cancer therapy. This study provides a paradigm of TME responsive theranostics under NIR-II light irradiation.

Long-term outcome of microwave ablation for benign thyroid nodules: Over 48-month follow-up study.

Objectives: The short-term effects of microwave ablation (MWA) for the treatment of benign thyroid nodules (BTNs) were satisfactory in previous studies. However, as a slowly progressing disease, the long-term efficacy of MWA for BTNs at present is not clear. Our study aim was to assess the long-term results of MWA for BTNs after a 48-month follow-up. Methods: From June 2015 to September 2017, 148 patients had 148 BTNs. All patients were from the China-Japan Union Hospital of Jilin University. Careful ultrasound examinations were performed 1 day, 1 month, 3 months, 6 months, 12 months, and every 6 months after MWA. The volume, volume reduction rate (VRR), recurrence rate of the ablated area and thyroid function were recorded. Results: The mean volumes of the 148 nodules were 15.6 ± 9.4 cm3 (range: 1.3-48.9 cm3) and 0.6 ± 0.6 cm3 (range: 0-3.5 cm3) before and 48 months after MWA, respectively, with a nodule VRR of 96.9 ± 2.5% (range: 90.4-100%). Two patients (1.35%) had recurrence after MWA. Compared with thyroid function before MWA, no significant variation was observed after MWA. Five patients experienced complications (3.38%): two patients (1.35%) had bleeding, two patients (1.35%) had ear pain and toothache during MWA, and one patient (0.68%) had hoarseness after MWA. No cases of oesophageal injury, tracheal injury, infection, skin burns, etc., were reported during or after MWA. Conclusions: Based on a long-term follow-up, MWA is an effective method for treating BTNs and is expected to be a potential first-line treatment.

Long non-coding RNA DUXAP8 promotes the cell proliferation, migration, and invasion of papillary thyroid carcinoma via miR-223-3p mediated regulation of CXCR4.

Papillary thyroid carcinoma (PTC) is a differentiated type of thyroid malignancy with a high incidence. Long non-coding RNA (lncRNA) DUXAP8 has been reported to participate in the proliferation, migration, and invasion of several cancer types. However, its association with PTC has not yet been reported. The current study aimed to investigate the role of DUXAP8 in PTC and revealed the underlying mechanisms. The expression of DUXAP8 was knocked down in two PTC cell lines and the effects of DUXAP8 on the PTC biological behavior were examined by cell counting kit-8 (CCK-8), wound healing, and transwell invasion assays. Luciferase reporter assay was used to detect the binding activity between miR-223-3p and DUXAP8. We found that knockdown of DUXAP8 inhibited the proliferation, migration, and invasion of PTC cells. DUXAP8 could sponge miR-223-3p through the specific binding site. CXCR4 was a target of miR-223-3p. The malignant phenotypes of the PTC cells were suppressed by the over-expression of miR-223-3p. Moreover, miR-223-3p inhibition or CXCR4 over-expression partly restored the proliferation, migration, and invasion activities of DUXAP8-downregulated PTC cells. The results evidenced that DUXAP8 acted as an oncogene in PTC, these effects seemed to partly dependent on the miR-223-3p/CXCR4 axis.

HOXB-AS1 accelerates the tumorigenesis of glioblastoma via modulation of HOBX2 and HOBX3 at transcriptional and posttranscriptional levels.

Glioblastoma (GBM) is the most universal and invasive brain tumor among adults. Increasing studies have reported that long noncoding RNAs play vital roles in regulating downstream molecules at the transcriptional or posttranscriptional level in tumor progression. The purpose of the current research was to inquire the modulation mechanism by which homeobox B cluster antisense RNA 1 (HOXB-AS1) functioned in GBM. Our study first discovered the lifted expression of HOXB-AS1 and its nearby genes HOXB2 and HOXB3 in GBM and the positive relationship between HOXB-AS1 and HOXB2 or HOXB3. Loss-of-function assays and in vivo study detected that silencing of HOXB-AS1, HOXB2, or HOXB3 restrained the proliferation and induced the apoptosis in GBM. In addition, mechanism experiments demonstrated that HOXB-AS1 recruited interleukin enhancer-binding factor 3 (ILF3) to regulate HOXB2 and HOXB3 expression at the transcriptional level, and HOXB-AS1 sponged miR-186-5p to modulate HOXB2 and HOXB3 expression at posttranscriptional level. Finally, the regulatory mechanism of HOXB-AS1 in GBM was certified through rescue experiments. Our results indicated that HOXB-AS1 boost the HOXB2 or HOXB3 expression at the transcriptional and posttranscriptional levels. We detected the HOXB-AS1-ILF3-HOXB2/HOXB3 axis and HOXB-AS1-miR-186-5p-HOXB2/HOXB3 axis driving the GBM progression, which might generate more effective diagnostic biomarkers and therapeutic targets for patients with GBM.

Long noncoding RNA HNF1A-AS1 regulates proliferation and apoptosis of glioma through activation of the JNK signaling pathway via miR-363-3p/MAP2K4.

Long noncoding RNAs (lncRNAs) have been proven to exert important functions in the various biological processes of human cancers. It has been reported that lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A-AS1) was abnormally expressed and played a role in the initiation and development of various human cancers. In this study, we confirmed that the expression level of HNF1A-AS1 was increased in glioma tissues and cells. Knockdown of HNF1A-AS1 inhibited cell proliferation and promoted cell apoptosis in glioma. Then, we disclosed the downregulation of miR-363-3p in glioma tissues and cell lines. The interaction between HNF1A-AS1 and miR-363-3p was identified in glioma cells. Furthermore, an inverse correlation between HNF1A-AS1 and miR-363-3p was observed in glioma tissues. Afterwards, we recognized that MAP2K4 was a direct target of miR-363-3p. The expression of MAP2K4 was negatively correlated with miR-363-3p while positively related to HNF1A-AS1 in glioma tissues. We also found the regulatory effect of HNF1A-AS1 on the MAP2K4-dependent JNK signaling pathway. All findings indicated that HNF1A-AS1 induces the upregulation of MAP2K4 to activate the JNK signaling pathway to promote glioma cell growth by acting as a miR-363-3p sponge.

The efficacy and safety of microwave ablation versus lobectomy for the treatment of benign thyroid nodules greater than 4 cm.

PURPOSE: To evaluate the safety and effectiveness of microwave ablation (MWA) versus lobectomy for the treatment of benign thyroid nodules > 4 cm. METHODS: We retrospectively analyzed the data of 48 patients who underwent MWA and 53 patients who underwent lobectomy to treat benign thyroid nodules > 4 cm. The patients were followed up for 12 months. The volume reduction ratio (VRR) was calculated. The operation time, incision length, hospitalization time, complications, thyroid function, symptoms, and cosmetic improvement were analyzed and compared between the two groups. RESULTS: During the 12-month follow-up, the mean nodule volume in the MWA group was reduced from 36.1 ± 23.1 to 4.0 ± 4.1 ml, and the mean VRR of the nodules was 90 ± 5% in the MWA group, which was comparable with that in the surgery group. No significant postoperative change in thyroid function was observed in the MWA group. Compared with the surgery group, the incidence of complications and postoperative pain in the MWA group were lower, the operation time, incision length, and hospitalization time in the MWA group were shorter, and satisfaction with the esthetic results in the MWA group was greater. CONCLUSION: MWA is safe and effective for the treatment of benign thyroid nodules > 4 cm. Moreover, MWA is associated with a faster recovery, fewer complications, better protection of thyroid function, and superior esthetic results relative to thyroid lobectomy.

Effects of Microwave Ablation on Papillary Thyroid Microcarcinoma: A Five-Year Follow-Up Report.

Background: Some researchers have achieved favorable efficacy in the treatment of primary papillary thyroid microcarcinoma (PTMC) using microwave ablation (MWA). However, as PTMC is a slowly progressing disease, a long follow-up period is required to confirm treatment efficacy. Our study aim was to investigate the long-term efficacy and safety of ultrasound (US)-guided MWA in PTMC. Methods: In this study, 41 patients with thyroid masses (41 nodules) were diagnosed with PTMC by fine-needle aspiration or core needle biopsy. They underwent US-guided MWA. Preablation ultrasonic images of the thyroid nodules were collected, and the volumes were measured. The patients had follow-up at 1, 3, 6, and 12 months in the first year and every 6 months from the second year on, after MWA. The volume reduction rates (VRRs) of the thyroid nodules were analyzed. Results: In total, 40 of 41 nodules were completely ablated by MWA. After 60 months of follow-up, the volume significantly decreased from a median of 55.78 mm3 (quartile: 21.50, 112.20 mm3) to 0 mm3 (0, 0 mm3) (p < 0.001), with a VRR of 99.37% ± 4.02%. Two patients developed hoarseness after ablation; one recovered within 10 minutes, and the hoarseness in the other patient resolved 2 months after the ablation. No recurrence, metastatic cervical lymph nodes, or distal metastasis was found during the follow-up period. Conclusions: In this five-year follow-up, MWA presented favorable efficacy with satisfactory safety for the treatment of PTMC. It should be considered an alternative therapy to surgery and active surveillance for solitary PTMC.

Enhanced proton conductivity of metal organic framework at low humidity by improvement in water retention.

A series of composites have been fabricated by introducing ionic liquid (IL) (ship) into chromium terephthalate MIL-101 (bottle) by ship-in-bottle method (IL@MIL-101s), the resulting IL@MIL-101s are endowed to high water retention, which is essential to proton conducting on multiple energy-involved applications at the low relative humidity (RH). The humidifying IL can lower water loss and increase water uptake, and thus improves water retention properties of the composites aided by the mesoporous MIL-101 at low RH. The hydropenic proton transfer pathways are modeled inside MOF and between IL-MOF, diminishing energy barrier routes for proton hopping, and thus a promotive proton transfer is rendered via Grotthuss mechanism. Specially, the IL@MIL-101 (SIB-3) unfolds a high proton conductivity (σ = 4.4 × 10-2 S cm-1) at RH as low as ~23%, five orders of magnitude increase than that of parent MIL-101 (1.1 × 10-7 S cm-1) at 323 K. Besides, IL@MIL-101s as fillers are incorporated into polymer blends to form hybrid membranes, appearing the relatively high proton conductivity (4.3 × 10-3 S cm-1) under ~23% RH at 323 K.

RAD21 inhibited transcription of tumor suppressor MIR4697HG and led to glioma tumorigenesis.

BACKGROUND: Studies have revealed the aberrant expression of lncRNAs is responsible for human carcinogenesis. MIR4697 host gene (MIR4697HG) is an upregulated lncRNA that promoted cell growth and metastasis in other cancers. In this study, we tested the expression of MIR4697HG in glioma cells and detected the comparatively down-regulated expression. RAD1 is an upstream regulator for MIR4697HG. This study aimed at exploring the regulatory mechanism and function of RAD1/MIR4697HG/PRR12 axis in glioma. METHODS: We profiled the expression of MIR4697HG in glioblastoma multiforme (GBM) tissues according to GEPIA database as well as in glioma cells by qPCR. Functional experiments confirmed relevant role of MIR4697HG in regulating glioma cell proliferation and migration. We also carried out luciferase reporter assay, pull down assay and RIP assay to verify the location and interaction among the indicated RNA molecules. RESULTS: The expression of MIR4697HG is down-regulated significantly in glioma cells due to the up-regulated expression of RAD21. MiR-766-5p was identified functioning as a sponge for MIR4697HG and is sequestered by MIR4697HG. We also found either miR-766-5p inhibitor or PRR12 knockdown rescued the function depletion caused by MIR4697HG overexpression. In all, the down-regulated expression of MIR4697HG inhibited PRR12 to suppress glioma and led to the deterioration of glioma. CONCLUSION: RAD21-induced down-regulated expression of MIR4697HG is correlated with aggravation of glioma. The MIR4697HG/miR-766-5p/PRR12 axis predicts poor results in glioma and MIR4697HG could be considered as a promising biomarker for diagnosis and treatment of glioma.

PSMB8-AS1 activated by ELK1 promotes cell proliferation in glioma via regulating miR-574-5p/RAB10.

Long noncoding RNAs (lncRNAs) get great involvements in the development of countless cancers. Nonetheless, the deep molecular mechanism by which lncRNA regulates the formation of glioma is unclear. In our study, the expression of PSMB8-AS1 was dramatically upregulated in glioma tissues and cells, further, PSMB8-AS1 silencing restrained cell proliferation in glioma, and the results of PSMB8-AS1 overexpression were opposite. Moreover, PSMB8-AS1 could bind with miR-574-5p, which was low expressed in glioma cells. In addition, RAB10 acted the target gene of miR-574-5p, and PSMB8-AS1 could regulate RAB10 via modulating miR-574-5p. Besides, miR-574-5p inhibitor/mimics remedied the repressive/simulative role of PSMB8-AS1 depletion/overexpression, and RAB10 downregulation/upregulation reversed the encouraging/blocked function caused by miR-574-5p inhibitor/mimics in PSMB8-AS1 depletion/overexpression transfected glioma cells. Additionally, ELK1, a transcription factor, could active PSMB8-AS1 expression. To be concluded, PSMB8-AS1 activated by ELK1 promotes cell proliferation in glioma via regulating miR-574-5p/RAB10, which may be contributory to find new targets to treat glioma.

Comparison and preliminary discussion of the reasons for the differences in diagnostic performance and unnecessary FNA biopsies between the ACR TIRADS and 2015 ATA guidelines.

OBJECTIVES: (1) To compare the American College of Radiology (ACR) thyroid imaging reporting and data system (TIRADS) and American Thyroid Association (ATA) guidelines for thyroid nodules with regard to diagnostic performance and effectiveness at reducing the number of fine-needle aspiration (FNA) biopsies and to preliminarily discuss the reasons for the differences and (2) to compare the diagnostic performance of the two guidelines in the subgroup of nodules <1 cm in diameter. MATERIALS AND METHODS: In the present study, 1000 thyroid nodules in 894 consecutive patients with final diagnoses were included; these thyroid nodules were investigated via FNA biopsies in our hospital. The ultrasound (US) features of the thyroid nodules were reviewed and stratified according to the categories defined by the ACR TIRADS and ATA guidelines. RESULTS: Compared with the ACR TIRADS guidelines, the ATA guidelines had a higher sensitivity (93.4% (P < 0.001)) and a larger negative predictive value (NPV) (85.3% (P= 0.034)). Compared with the ATA guidelines, the ACR TIRADS guidelines had a higher specificity (66.0% (P < 0.001)), a greater PPV (73.6% (P= 0.001)), and greater accuracy (75.5% (P= 0.017)). Compared with the ATA guidelines, the ACR TIRADS guidelines resulted in significantly fewer unnecessary FNA biopsies (P= 0.007). CONCLUSIONS: This study suggests that both the ACR TIRADS and ATA guidelines have unique strengths with regard to their diagnostic performance. In terms of reducing the number of FNA biopsies, the ACR TIRADS guidelines were superior to the ATA guidelines.

Preliminary report of microwave ablation for the primary papillary thyroid microcarcinoma: a large-cohort of 185 patients feasibility study.

PURPOSE: To assess the safety and efficacy of microwave ablation (MWA) for primary papillary thyroid microcarcinoma (PTMC) with a large sample of 185 patients. METHODS: A total of 185 patients underwent MWA for 206 primary PTMC nodules. They received ultrasound follow-up at 1, 3, 6, and 12 months after MWA and every 6 months thereafter. Nodule volumes were calculated at each follow-up and compared with those before MWA. Additionally, the volume reduction rate (VRR) of the nodules was calculated. Patients' thyroid functions were tested before and 1 month after MWA. RESULTS: The mean follow-up time of the 185 patients was 20.7 ± 8.8 months (range 12-36 months). During the follow-up period, the mean volume of the 206 nodules was 100.1 ± 92.9 mm3 (range 3.6-423.9) before MWA, which decreased to 2.2 ± 5.6 mm3 (range 0-20.3 mm3) after MWA (P = 0.000). The mean VRR of the nodules was 98.65 ± 3.60% after MWA (range 83.85-100%). One hundred and seventy four of 206 nodules (84.5%) were fully absorbed. Compared with the preoperative results, no significant variation in thyroid function was observed 1 month after MWA. Thirty-eight patients (20.5%) had different types of complications, ranging from minor to major. Five patients (2.7%) had hoarseness, 11 patients (5.9%) had bleeding, 21 patients (11.4%) had earache or toothache, and one patient had another lesion 1 month after MWA. CONCLUSIONS: This preliminary study suggests that MWA is safe and effective in the treatment of primary PTMC and offers a new alternative for clinical treatment.