Diverse functions of TRIB3 in cancers and its potential as a therapeutic target.

Currently, cancer is the second leading cause of death worldwide, and potential targeted drugs and molecular pathways for cancer development and progression have been a hot research topic worldwide. In recent years, the importance of kinase superfamily in diseases has been well demonstrated by studies on various molecular mechanisms of kinases and successful application of their inhibitors in diseases. Pseudokinases are members of kinase superfamily, which have been increasingly documented to play a crucial role in cancers year after year. As a member of pseudokinases, tribbles homolog 3 (TRIB3) also exerts diverse functions in different cancers through different interacting proteins and molecular pathways, especially in tumor immunity, stemness, drug resistance, metabolism and autophagy. In addition, peptide drugs targeting TRIB3 have high specificity in preclinical studies, which shows great promise for TRIB3 application in diseases including cancers. In this review, we dissect diverse functions played by TRIB3 in different cancers, describing the underlying mechanisms in detail. Notably, inhibitors and agonists currently available for TRIB3 are discussed, indicating potential for TRIB3 as a therapeutic target.

Acute aortic dissection complicated with hemorrhagic aortopulmonary artery sheath: a review of the literature.

A hemorrhagic aortopulmonary artery sheath (HAPS) is an infrequent and critical complication of aortic dissection (AD), which is caused by a hematoma extending through the ruptured aortic wall into the aortopulmonary artery sheath. The adventitial hematoma might narrow or even occlude the lumen of the pulmonary arteries and extend into the pulmonary interstitium and alveoli. The prompt and accurate recognition of HAPS on computed tomography (CT) is crucial and might assist in the diagnosis of unidentifiable AD. HAPS was manifested as high attenuation areas surrounded the pulmonary arteries without enhancement on CT; even thickened bronchovascular sheath and ground-glass consolidations surrounded bronchovascular distribution, which might be associated with the prognosis. Aggressive and effective surgical treatment is the primary determinant of short-term survival.

Visual Quantitative Detection of Glutathione and Cholesterol in Human Blood Based on the Thiol-Ene Click Reaction-Triggered Wettability Change of the Interface.

Herein, we proposed an innovative visual quantitative sensing strategy based on thiol-ene click chemistry and the capillary action principle. A triethoxyvinylsilane (VTEO)- or mercaptopropylsilatrane (MPS)-modified interface was prepared for analyte recognition. Target analyte molecules containing thiol groups or C═C double bonds are coupled to the VTEO- or MPS-modified inner surface of the glass capillary tube via a thiol-ene click reaction, respectively. Then, the molecular recognition events were transformed into the wettability change of the inner wall of the glass capillary. The concentration of the target molecules was quantified by reading the height change of the water column in the capillary tube. As a proof of concept, this strategy was successfully used to build visual quantitative sensors for detecting glutathione and cholesterol. In addition, this strategy showed a good anti-interference ability to complex biological fluids and realized sensitive glutathione (GSH) and cholesterol detection in real human blood samples.

Venous thromboembolic events in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: High incidence of venous thromboembolic complications in coronavirus disease 2019 (COVID-19) patients was noted recently. OBJECTIVE: This study aimed to explore the factors associated with prevalence of venous thromboembolism (VTE) in COVID-19 patients. METHODS: A literature search was conducted in several online databases. Fixed effects meta-analysis was performed for the factors associated with prevalence of VTE in COVID-19 patients. RESULTS: A total of 39 studies were analysed in this analysis. The incidence of pulmonary embolism and VTE in severe COVID-19 patients were 17% (95% CI, 13-21%) and 42% (95% CI, 25-60%), respectively. VTE were more common among individuals with COVID-19 of advance age. Male COVID-19 patients are more likely to experience VTE. Higher levels of white blood cell (WBC; WMD = 1.34 × 109/L; 95% CI, 0.84-1.84 × 109/L), D-dimer (WMD = 4.21 µg/ml; 95% CI, 3.77-4.66 µg/ml), activated partial thromboplastin time (APTT; WMD = 2.03 s; 95% CI, 0.83-3.24 s), fibrinogen (WMD = 0.49 µg/ml; 95% CI, 0.18-0.79 g/L) and C-reactive protein (CRP; WMD = 21.89 mg/L; 95% CI, 11.44-32.34 mg/L) were commonly noted in COVID-19 patients with VTE. Patients with lower level of lymphocyte (WMD = -0.15 × 109/L; 95% CI, -0.23--0.07 × 109/L) was at high risk of developing VTE. The incidence of severe condition (OR = 2.66; 95% CI, 1.95-3.62) was more likely to occur among COVID-19 patients who developed VTE. CONCLUSION: VTE is a common complication in severe COVID-19 patients and thromboembolic events are also associated with adverse outcomes.

Protein mass spectrometry reveals lycorine exerting anti-multiple-myeloma effect by acting on VDAC2 and causing mitochondrial abnormalities.

OBJECTIVE: Two-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF mass spectrometry were performed to compare the proteomic alterations of lycorine-treated and control cells to further investigate the anti-multiple myeloma (MM) mechanisms of lycorine. RESULTS: Mass spectrometry results showed that after lycorine treatment of MM cells, 42% of the differentially expressed proteins had subcellular localization, mainly, on mitochondria. Voltage-dependent anion-selective channel protein 2 (VDAC2), the most abundant protein in the outer mitochondrial membrane, was up-regulated after treatment with lycorine and was subsequently verified by western blot analysis. Further studies on mitochondria found that lycorine was able to increase abnormal mitochondria and increase mitochondrial membrane potential. CONCLUSIONS: Lycorine can achieve the effect of resisting multiple myeloma by acting on VDAC2 and causing mitochondrial abnormalities.

Curcumol and FTY720 synergistically induce apoptosis and differentiation in chronic myelomonocytic leukemia via multiple signaling pathways.

Chronic myelomonocytic leukemia (CML) is a myeloid tumor characterized by MDS (myelodysplastic syndrome) and MPN (myeloproliferative neoplasms). Allogeneic hematopoietic stem cell transplantation, chemotherapy, interferon, and targeted therapy are the main treatment methods for CML. Tyrosine kinase inhibitors (TKIs) are also a treatment option, and patients are currently recommended to take these drugs throughout their lives to prevent CML recurrence. Therefore, there is a need to investigate and identify other potential chemotherapy drugs. Currently, research on CML treatment with a single drug has shown little progress. Fingolimod (FTY720), an FDA-approved drug used to treat relapsing multiple sclerosis, has also shown great potential in the treatment of lymphocytic leukemia. In our study, we find that FTY720 and curcumol have a significant inhibitory effect on K562 cells, K562/ADR cells, and CD34+ cells from CML patients. RNAseq data analysis shows that regulation of apoptosis and differentiation pathways are key pathways in this process. Besides, BCR/ABL-Jak2/STAT3 signaling, PI3K/Akt-Jnk signaling, and activation of BH3-only genes are involved in CML inhibition. In a K562 xenograft mouse model, therapy with curcumol and FTY720 led to significant inhibition of tumor growth and induction of apoptosis. To summarize, curcumol and FTY720 synergistically inhibit proliferation involved in differentiation and induce apoptosis in CML cells. Therefore, synergistic treatment with two drugs could be the next choice of treatment for CML.

The Wee1 kinase inhibitor MK1775 suppresses cell growth, attenuates stemness and synergises with bortezomib in multiple myeloma.

Multiple myeloma stem-like cells (MMSCs) are responsible for initiation and relapse, though novel treatment paradigms that effectively eradicate MMSCs are yet to be developed. Selective inhibition of the cell cycle regulatory kinase Wee1 by MK1775 is being explored as a potential anti-cancer therapeutic. We report that higher expression of Wee1 is correlated with poor survival in multiple myeloma (MM). The MM models and patient-derived CD138+ plasma cells are particularly sensitive to the growth-inhibitory effects of the Wee1 inhibitor MK1775. MK1775 induces Mus81-Eme1 endonuclease-mediated DNA damage in S-phase cell cycle that results in a blockade of replication and then apoptosis. Furthermore, MK1775 strongly suppresses the features of stemness in vitro, in vivo and in primary CD138+ cells by decreasing ALDH1+ cell fraction and the expression of ALDH1. In addition, co-treatment of MK1775 with bortezomib is synergistic in vitro and in vivo. Bortezomib, although it enhances ALDH1+ cells, when combined with MK1775 abrogates this stimulatory effect on stemness. Considering MM as an invariably incurable malignancy due to the presence of heterogenic myeloma stem-like cells, our study presents inhibition of Wee1 as a promising targeted therapy for MM and provides a compelling rationale to further investigate the activity of MK1775 against myeloma in clinical settings.

Lycorine targets multiple myeloma stem cell-like cells by inhibition of Wnt/ß-catenin pathway.

Multiple myeloma (MM) is characterised by the proliferation and accumulation of malignant plasma cells in the bone marrow. Despite the progress in treatment over the last few years, MM remains incurable and the majority of patients relapse. MM stem-like cells (MMSCs) have been considered as the main reason for drug resistance and eventual relapse. Currently, therapeutic agents are not enough to eradicate MMSCs, and finding effective strategies to eradicate MMSCs may improve the outcome of patients. Here we showed that lycorine, a natural compound from the Amaryllidaceae species, effectively inhibits the proliferation of myeloma cells from cell lines or patients, mainly through decreasing ALDH1+ cells. Mechanistically, lycorine decreases the MMSC population through inhibition of the Wnt/ß-catenin pathway by reducing the ß-catenin protein level. Moreover, lycorine could overcome the increasing proportion of ALDH1+ cells caused by bortezomib (BTZ) treatment, and a combination BTZ and lycorine have a synergistic effect on anti-myeloma cells. Furthermore, we found a similar reduction of MMSC characteristics by lycorine in BTZ-resistant MM cells and primary CD138+ plasma cells. Collectively, our findings indicate lycorine as a promising agent to target MMSCs to overcome the drug resistance of BTZ, and that, alone or in combination with BTZ, lycorine is a potential therapeutic strategy for MM treatments.

Gemcitabine inhibits cisplatin resistance in cisplatin-resistant A549 cells by upregulating trx-interacting protein and inducing cell cycle arrest.

Cisplatin is a main chemotherapeutic drug used to treat non-small-cell lung cancer patients. However, these patients commonly face cisplatin resistance. The roles and underlying mechanisms of gemcitabine, irinotecan, pemetrexed and docetaxel used as single agents or combined with cisplatin for overcoming cisplatin-resistant non-small-cell lung cancer were explored in this study. MTT assays showed that gemcitabine alone exhibited stronger cytotoxicity on cisplatin-resistant A549 cells than irinotecan, pemetrexed and docetaxel. Meanwhile, gemcitabine combined with cisplatin showed a synergistic inhibitory effect on cisplatin-resistant cells. RNA sequencing and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis showed that cell cycle signaling pathways and trx-interacting protein were factors in the efficacy of the cotreatment. Flow cytometry and Western blot results showed that when cisplatin-resistant A549 cells were cotreated with gemcitabine and cisplatin, G0/G1 phase arrest occurred, and trx-interacting protein was upregulated. Silencing trx-interacting protein attenuated the response of the resistant cells to the drug combination. A trx-interacting protein agonist together with cisplatin showed an additive cytotoxic effect on the resistant cells compared with cisplatin alone. The gemcitabine and cisplatin combination, compared to gemcitabine or PBS alone, markedly suppressed the growth of cisplatin-resistant A549 tumors in vivo, accompanied by an increase in trx-interacting protein and a decrease in Ki67 expression. Therefore, we concluded that gemcitabine and cisplatin, as an FDA-approved combination, is a viable therapy for cisplatin-resistant non-small-cell lung cancer ex vivo and in vivo.

Deubiquitylase USP7 regulates human terminal erythroid differentiation by stabilizing GATA1.

Ubiquitination is an enzymatic post-translational modification that affects protein fate. The ubiquitin-proteasome system (UPS) was first discovered in reticulocytes where it plays important roles in reticulocyte maturation. Recent studies have revealed that ubiquitination is a dynamic and reversible process and that deubiquitylases are capable of removing ubiquitin from their protein substrates. Given the fact that the UPS is highly active in reticulocytes, it is speculated that deubiquitylases may play important roles in erythropoiesis. Yet, the role of deubiquitylases in erythropoiesis remains largely unexplored. In the present study, we found that the expression of deubiquitylase USP7 is significantly increased during human terminal erythroid differentiation. We further showed that interfering with USP7 function, either by short hairpin RNA-mediated knockdown or USP7-specific inhibitors, impaired human terminal erythroid differentiation due to decreased GATA1 level and that restoration of GATA1 levels rescued the differentiation defect. Mechanistically, USP7 deficiency led to a decreased GATA1 protein level that could be reversed by proteasome inhibitors. Furthermore, USP7 interacts directly with GATA1 and catalyzes the removal of K48-linked poly ubiquitylation chains conjugated onto GATA1, thereby stabilizing GATA1 protein. Collectively, our findings have identified an important role of a deubiquitylase in human terminal erythroid differentiation by stabilizing GATA1, the master regulator of erythropoiesis.

Association between high-resolution MRI-detected extramural vascular invasion and tumour microcirculation estimated by dynamic contrast-enhanced MRI in rectal cancer: preliminary results.

BACKGROUND: To determine whether magnetic resonance imaging (MRI)-detected extramural vascular invasion (mrEMVI) status is associated with quantitative perfusion parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) in rectal cancer. METHODS: Seventy-two patients with rectal adenocarcinoma who underwent curative surgery alone within 2 weeks following rectal MRI were enrolled in this retrospective study. mrEMVI status was determined based on high-resolution MRI. The quantitative perfusion parameters (Ktrans, kep and ve) derived from DCE-MRI were calculated from all sections containing tumours. DCE-MRI parameters and clinicopathological variables in patients with different mrEMVI statuses were compared. RESULTS: For patients who were mrEMVI positive, the tumours demonstrated significantly lower kep values (P = 0.012) and higher ve values (P = 0.021) than tumours of patients who were mrEMVI negative, while the Ktrans value displayed no significant difference (P = 0.390). The patients who were mrEMVI positive had larger tumour size, higher pathological tumour stage and increased regional nodal metastases compared to those who were mrEMVI negative (2.9 cm vs. 3.5 cm, P = 0.011; 63.8% vs. 92.0%, P = 0.010; 36.2% vs. 76.0%, P = 0.001; respectively). CONCLUSIONS: This study demonstrated for the first time that tumour microcirculation is altered in mrEMVI-positive patients with rectal adenocarcinoma, as evidenced by significantly lower kep and higher ve values. In addition, these patients were more likely to have a larger tumour size, a higher pathological tumour stage and regional nodal metastases than mrEMVI-negative patients.

Role of Quantitative Dynamic Contrast-Enhanced MRI in Evaluating Regional Lymph Nodes With a Short-Axis Diameter of Less Than 5 mm in Rectal Cancer.

OBJECTIVE: The aim of this study was to discriminate metastatic from nonmetastatic regional lymph nodes (LNs) with short-axis diameters of less than 5 mm in rectal cancer using quantitative parameters derived from dynamic contrast-enhanced (DCE) MRI. SUBJECTS AND METHODS: Sixty-five LNs from 122 patients were evaluated, including malignant LNs (n = 27) and benign LNs (n = 38). The following parameters were assessed: the forward volume transfer constant (Ktrans), reverse volume transfer constant (kep), fractional extravascular extracellular space volume (Ve), short-axis diameter, long-axis diameter, and short- to long-axis diameter ratio. ROC curves were used to analyze statistically significant parameters. RESULTS: Metastatic LNs exhibited a lower Ktrans than did nonmetastatic LNs (p < 0.001), but the other parameters were not significantly different between the two groups. The AUC of the Ktrans was 0.732, with a 95% CI of 0.610-0.854, and the diagnostic cutoff value was 0.088 min-1 (sensitivity, 60.5%; specificity, 81.5%). CONCLUSION: Ktrans had moderate diagnostic performance in assessing small regional LNs in rectal cancer and appears to be a useful predictor when distinguishing malignant LNs from benign LNs only by morphology is difficult.

Perfusion-sensitive parameters of intravoxel incoherent motion MRI in rectal cancer: evaluation of reproducibility and correlation with dynamic contrast-enhanced MRI.

BACKGROUND: Intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) acquires tumor perfusion information without injection of contrast medium, which is promising in tumor assessment. However, its consistency with dynamic contrast-enhanced MRI (DCE-MRI), a more widely used method for tumor perfusion evaluation, is not revealed in rectal cancer. PURPOSE: In this study, we aimed to investigate the correlation of perfusion-sensitive parameters derived from IVIM-MRI with DCE-MRI and measurement reproducibility of IVIM-MRI parameters in rectal cancer. MATERIAL AND METHODS: Forty-seven rectal cancer patients underwent IVIM-MRI with 16 b-values and DCE-MRI. The perfusion fraction ( f), pseudo-diffusion coefficient ( D*), and f· D* were measured by two radiologists independently and correlated with the transfer constant ( Ktrans), reflux constant ( kep), and extravascular extracellular fractional volume ( ve) obtained from DCE-MRI. RESULTS: Pearson's correlation analyses of IVIM-MRI and DCE-MRI parameters showed fair to moderate correlation between f and Ktrans ( r = 0.461, P = 0.001), followed by f and kep ( r = 0.430, P = 0.003), f·D*, and Ktrans ( r = 0.425, P = 0.003), f·D*, and kep ( r = 0.384, P = 0.008). There was no significant correlation between ve and f, ve and D*, ve and f· D*, D* and Ktrans, and D* and kep. The reproducibility of IVIM-MRI measurements was moderate. For parameter f, intraclass correlation coefficient (ICC) = 0.71 (0.53-0.82), coefficient of variation (CV) = 13.05 ± 0.02%, limit of agreement (LoA) = -0.05-0.04; for parameter D*, ICC = 0.55 (0.32-0.72), CV = 20.28 ± 3.23%, LoA = -9.6-8.4. CONCLUSION: Perfusion-sensitive parameters derived from IVIM-MRI correlated fairly to moderately with DCE-MRI in rectal cancer patients and showed moderate measurement reproducibility. IVIM-MRI supplements routine high-resolution MRI without contrast enhancement to provide information of tumor microcirculation.

Targeting c-met receptor tyrosine kinase by the DNA aptamer SL1 as a potential novel therapeutic option for myeloma.

Hepatocyte growth factor (HGF)/c-met pathway activation has been implicated in the pathogenesis of multiple myeloma (MM), and blocking this pathway has been considered a rational therapeutic strategy for treating MM. Aptamers are single-stranded nucleic acid molecules that fold into complex 3D structures and bind to a variety of targets. Recently, it was reported that DNA aptamer SL1 exhibited high specificity and affinity for c-met and inhibited HGF/c-met signaling in SNU-5 cells. However, as the first c-met-targeted DNA aptamer to be identified, application of SL1 to myeloma treatment requires further investigation. Here, we explore the potential application of SL1 in MM. Our results indicated that c-met expression is gradually increased in MM patients and contributes to poor outcomes. SL1 selectively bound to c-met-positive MM cells but not to normal B cells and suppressed the growth, migration and adhesion of MM cells in vitro in a co-culture model performed with HS5 cells, wherein SL1 inhibited HGF-induced activation of c-met signaling. In vivo and ex vivo fluorescence imaging showed that SL1 accumulated in the c-met positive tumour areas. In addition, SL1 was active against CD138+ primary MM cells and displayed a synergistic inhibition effect with bortezomib. Collectively, our data suggested that SL1 could be beneficial as a c-met targeted antagonist in MM.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging of Primary Rectal Carcinoma: Correlation with Histopathology.

BACKGROUND Comprehensive and precise assessment of rectal carcinoma is crucial before surgery to plan an individual treatment strategy. New functional techniques, such as intravoxel incoherent motion (IVIM), have emerged and could lead to more detailed information. The aim of this study was to evaluate the difference between the rectal tumor parenchyma and normal wall by IVIM and to explore the correlations of IVIM parameters and histopathology. MATERIAL AND METHODS We prospectively enrolled 128 patients with pathologically proven rectal non-mucinous carcinoma with differentiation degree and 16 patients with mucinous carcinoma. All patients underwent routine MR examination and IVIM sequence. The IVIM maps were automatically generated and 3 ROIs were drawn on the maximal rectal tumor parenchyma and normal rectal wall. The Wilcoxon signed rank test, t test, Mann-Whitney U test, and Spearman's rank correlation test were performed. RESULTS All IVIM parameters demonstrated the difference between rectal tumor parenchyma and normal wall (PD<0.001; PD*=0.014; Pf<0.001). Poorly differentiated carcinoma had a significantly lower f value (Pf=0.049) than well/moderately-differentiated carcinoma. In addition, mucinous carcinoma had a higher D (PD=0.001) and a lower D* value (PD*=0.001) than non-mucinous carcinoma. Correlation analysis between IVIM parameters and histopathology showed that D (|r|=0.538, PD=0.000) and D* (|r|=0.267, PD*=0.001) had statistically significant correlations with histological type and f (|r|=0.175, Pf=0.048) was significantly correlated with differentiation degree. CONCLUSIONS The IVIM parameters of rectal tumor parenchyma and normal wall were significantly different. D appears to be a valid and promising parameter to indicate histological features of rectal carcinoma.

4.1N is involved in a flotillin-1/ß-catenin/Wnt pathway and suppresses cell proliferation and migration in non-small cell lung cancer cell lines.

The membrane-cytoskeletal protein 4.1N has recently been proposed as a tumor suppressor in a number of cancers of epithelial origin, including non-small-cell lung cancer (NSCLC). However, the molecular mechanism associated with 4.1N tumor suppression remains has not been thoroughly characterized. In this study, 4.1N was shown to directly interact with the lipid raft marker flotillin-1 through its FERM and U2 domains in several different NSCLC cell lines using immunoprecipitation, co-immunoprecipitation and pull-down assays. Moreover, 4.1N silencing/overexpression experiments in paired 95C/95D cells that are of homologous origin but varying endogenous 4.1N expression (high expression in 95C cells, low expression in 95D cells) indicated that 4.1N is involved in the suppression of cell proliferation and migration through a flotillin-1/ß-catenin/Wnt pathway. Taken together, the findings of this study help to elucidate the novel tumor suppressor role of 4.1N in NSCLC.

Lycorine induces programmed necrosis in the multiple myeloma cell line ARH-77.

Lycorine, a natural alkaloid, has been widely reported to possess potential efficacy against cancer. However, the anti-multiple myeloma mechanism of lycorine is not fully understood. In this study, the results demonstrated that lycorine is effective against multiple myeloma cell line ARH-77 via inducing programmed necrosis. The mechanisms of lycorine on the multiple myeloma cell line ARH-77 are associated with G1 phase cell cycle arrest, mitochondrial dysfunction, reactive oxygen species (ROS) generation, ATP depletion, and DNA damage. Our results elucidate the new mechanism of lycorine against multiple myeloma.

Autophagy as a regulatory component of erythropoiesis.

Autophagy is a process that leads to the degradation of unnecessary or dysfunctional cellular components and long-lived protein aggregates. Erythropoiesis is a branch of hematopoietic differentiation by which mature red blood cells (RBCs) are generated from multi-potential hematopoietic stem cells (HSCs). Autophagy plays a critical role in the elimination of mitochondria, ribosomes and other organelles during erythroid terminal differentiation. Here, the modulators of autophagy that regulate erythroid differentiation were summarized, including autophagy-related (Atg) genes, the B-cell lymphoma 2 (Bcl-2) family member Bcl-2/adenovirus E1B 19 kDa interacting protein 3-like (Nix/Binp3L), transcription factors globin transcription factor 1 (GATA1) and forkhead box O3 (FoxO3), intermediary factor KRAB-associated protein1 (KAP1), and other modulators, such as focal adhesion kinase family-interacting protein of 200-kDa (FIP200), Ca2+ and 15-lipoxygenase. Understanding the modulators of autophagy in erythropoiesis will benefit the autophagy research field and facilitate the prevention and treatment of autophagy-related red blood cell disorders.

Aptamer TY04 inhibits the growth of multiple myeloma cells via cell cycle arrest.

The aptamer TY04 is a single-stranded DNA. However, its biological function has not been elucidated. Here, we found that TY04 specifically bound to multiple myeloma cells MM.1S, and some membrane proteins on the surface of MM.1S cells constituted the target molecules of TY04. TY04 inhibited the growth of multiple myeloma cell lines, induced cell cycle arrest in mitosis, and resulted in a significant accumulation of binucleated cells. Following TY04 treatment, a concomitant increase in CDK1 and cyclin B1 expression occurred. In addition, TY04 treatment also resulted in a significant downregulation of γ-tubulin. Considering the unique advantages of aptamers, TY04 shows great potential as a drug candidate to treat multiple myeloma.

CARE-radiology statement explanation and elaboration: reporting guideline for radiological case reports.

Despite the increasing number of radiological case reports, the majority lack a standardised methodology of writing and reporting. We therefore develop a reporting guideline for radiological case reports based on the CAse REport (CARE) statement. We established a multidisciplinary group of experts, comprising 40 radiologists, methodologists, journal editors and researchers, to develop a reporting guideline for radiological case reports according to the methodology recommended by the Enhancing the QUAlity and Transparency Of health Research network. The Delphi panel was requested to evaluate the significance of a list of elements for potential inclusion in a guideline for reporting mediation analyses. By reviewing the reporting guidelines and through discussion, we initially drafted 46 potential items. Following a Delphi survey and discussion, the final CARE-radiology checklist is comprised of 38 items in 16 domains. CARE-radiology is a comprehensive reporting guideline for radiological case reports developed using a rigorous methodology. We hope that compliance with CARE-radiology will help in the future to improve the completeness and quality of case reports in radiology.