COAP-Pd Catalyzed Asymmetric Formal [3+2] Cycloaddition for Optically Active Multistereogenic Spiro Cyclopentane-Indandiones Bearing Cyclic N-Sulfonyl Ketimine Skeletons.

We reported a chiral oxamide-phosphine ligand (COAP-Ph)-Pd-catalyzed asymmetric [3+2] cycloaddition reaction between vinyl cyclopropane compounds derived from 1,3-indanedione and 2-vinylcyclopropane-1,1-dicarboxylates with cyclic sulfonyl 1-azadienes. The corresponding reactions provided a series of enantiomerically active spiro cyclopentane-indandione and cyclopentane structures bearing three consecutive stereogenic centers in good yields with good diastereo- and enantioselectivity. The COAP-Pd complex serves not only to promote generation of chiral π-allyl-palladium intermediates and induce the asymmetry of the reaction, but also depress the background reaction.

Taxonomic notes on the genus Itea (Iteaceae).

The genus Itea (Iteaceae) is recognised as a genus with about 21 extant species of shrubs and trees. Within the genus, most species have oblong to elliptical leaves. The lanceolate and obolanceolate leaves are only found in three species, vix Iteaamoena Chun, Iteariparia Collett & Hemsl. and Iteatenuinervia S. Y. Liu. The results of our examination of literature, specimens and living plants in the wild have shown that Iteatenuinervia is conspecific with Iteariparia and is here reduced to a synonym of the latter species. The morphological description, colour pictures, voucher specimens, distribution map of Iteariparia and its related Iteaamoena, together with the morphological comparisons between the two species, are provided in this study.

Fuzzy PID control of permanent magnet synchronous motor electric steering engine by improved beetle antennae search algorithm.

The accuracy of control in permanent magnet synchronous motor system significantly affects overall mechanical structure safety. To satisfy high-performance control for the position servo of the electric steering engine, this study selects a suitable vector control model for permanent magnet synchronous motor. Additionally, an enhanced beetle antennae search algorithm is designed and employed to optimize the fuzzy proportional-integral-derivative controller. The hybrid fuzzy proportional-integral-derivative controller is then implemented in the control model of the permanent magnet synchronous motor, resulting in the establishment of a novel control model for the electric steering engine driven by the permanent magnet synchronous motor. The test results showed that root-mean-square error of this control model was 0.03 mm and 0.02 mm respectively under the conditions of sinusoidal response, square wave response and step response, which was obviously shorter than all the selected control models. In addition, the standard deviation of the control model designed in this study accounted for less than 4% of root-mean-square error of electric steering engine position under the sinusoidal response condition, so the calculation stability was high. The research results show that the designed control model has a certain reference value for improving servo control performance of permanent magnet synchronous motor.

Icariin restrains NLRP3 inflammasome-mediated Th2 immune responses and ameliorates atopic dermatitis through modulating a novel lncRNA MALAT1/miR-124-3p axis.

CONTEXT: Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases. OBJECTIVE: The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development. MATERIALS AND METHODS: BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin. RESULTS: Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses. DISCUSSION AND CONCLUSIONS: The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD.

Design and Screening of Fluorescent Probes Based upon Hemicyanine Dyes to Sensitively Respond to HSO3- in Living Cells.

SO2, a gas signaling molecule, can be produced endogenously in mitochondria. Its hydrolysate, HSO3-, plays a key role in food preservation, cardiovascular relaxation, and other fields, suggesting that it is important to achieve its detection. Here, based on the Michael addition mechanism, four hemicyanine dye fluorescent probes (ETN, ETB, STB, and EIB) were designed and synthesized for responding to HSO3-. We evaluated the reaction ability of different probes with HSO3- and tried to explain the reasons for the significantly different response effects between probes and HSO3- according to the structure-activity relationship. The influence of different substituents of probes on the properties of mitochondria-targeting was also discussed. Finally, we screened out ETN as the optimal HSO3- probe due to its high sensitivity, rapid reactivity, and good mitochondria-targeting, and it could sensitively respond to HSO3- in living cells. The LODs of ETN for HSO3- were calculated by both absorption and fluorescence methods, respectively, which were 2.727 and 0.823 µM. Our work provided valuable references for designing strategies and potential tools for response to SO2 derivatives in biosystems.

Cataract-causing Y204X mutation of crystallin protein CRYßB1 promotes its C-terminal degradation and higher-order oligomerization.

Crystallin proteins are a class of main structural proteins of the vertebrate eye lens, and their solubility and stability directly determine transparency and refractive power of the lens. Mutation in genes that encode these crystallin proteins is the most common cause for congenital cataracts. Despite extensive studies, the pathogenic and molecular mechanisms that effect congenital cataracts remain unclear. In this study, we identified a novel mutation in CRYBB1 from a congenital cataract family, and demonstrated that this mutation led to an early termination of mRNA translation, resulting in a 49-residue C-terminally truncated CRYßB1 protein. We show this mutant is susceptible to proteolysis, which allowed us to determine a 1.2-Å resolution crystal structure of CRYßB1 without the entire C-terminal domain. In this crystal lattice, we observed that two N-terminal domain monomers form a dimer that structurally resembles the WT monomer, but with different surface characteristics. Biochemical analyses and cell-based data also suggested that this mutant is significantly more liable to aggregate and degrade compared to WT CRYßB1. Taken together, our results provide an insight into the mechanism regarding how a mutant crystalin contributes to the development of congenital cataract possibly through alteration of inter-protein interactions that result in protein aggregation.

An opto-thermal approach for assembling yeast cells by laser heating of a trapped light absorbing particle.

Cell assembly has important applications in biomedical research, which can be achieved with laser-heating induced thermal convective flow. In this paper, an opto-thermal approach is developed to assemble the yeast cells dispersed in solution. At first, polystyrene (PS) microbeads are used instead of cells to explore the method of microparticle assembly. The PS microbeads and light absorbing particles (APs) are dispersed in solution and form a binary mixture system. Optical tweezers are used to trap an AP at the substrate glass of the sample cell. Due to the optothermal effect, the trapped AP is heated and a thermal gradient is generated, which induces a thermal convective flow. The convective flow drives the microbeads moving toward and assembling around the trapped AP. Then, the method is used to assemble the yeast cells. The results show that the initial concentration ratio of yeast cells to APs affects the eventual assembly pattern. The binary microparticles with different initial concentration ratios assemble into aggregates with different area ratios. The experiment and simulation results show that the dominant factor in the area ratio of yeast cells in the binary aggregate is the velocity ratio of the yeast cells to the APs. Our work provides an approach to assemble the cells, which has a potential application in the analysis of microbes.

Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.

Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulated in calcific areas. We further demonstrated TCF21 expression was increased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1ß and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21ECKO) mice, VD3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification.

Amorphous K-Buserite Microspheres for High-Performance Aqueous Zn-Ion Batteries and Hybrid Supercapacitors.

Aqueous Zn-ion batteries (AZIBs) and Zn-ion hybrid supercapacitors (AZHSCs) are considered promising energy-storage alternatives to Li-ion batteries due to the attractive merits of low-price and high-safety. However, the lack of suitable cathode materials always hinders their large-scale application. Herein, amorphous K-buserite microspheres (denoted as K-MnOx ) are reported as cathode materials for both AZIBs and AZHSCs, and the energy-storage mechanism is systematically revealed. It is found that K-MnOx is composed of rich amorphous K-buserite units, which can irreversibly be transformed into amorphous Zn-buserite units in the first discharge cycle. Innovatively, the transformed Zn-buserite acts as active materials in the following cycles and is highly active/stable for fast Zn-diffusion and superhigh pseudocapacitance, enabling the achievement of high-efficiency energy storage. In the AZIBs, K-MnOx delivers 306 mAh g-1 after 100 cycles at 0.1 A g-1 with 102% capacity retention, while in the AZHSCs, it shows 515.0/116.0 F g-1 at 0.15/20.0 A g-1 with 92.9% capacitance retention at 5.0 A g-1 after 20 000 cycles. Besides, the power/energy density of AZHSCs device can reach up to 16.94 kW kg-1 (at 20 A g-1 )/206.7 Wh kg-1 (at 0.15 A g-1 ). This work may provide some references for designing next-generation aqueous energy-storage devices with high energy/power density.

Morinda officinalis extract exhibits protective effects against atopic dermatitis by regulating the MALAT1/miR-590-5p/CCR7 axis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a genetic predisposition, and the traditional Chinese medicine Morinda officinalis and its roots are characterized with anti-inflammatory effects and have been used for the treatment of various disease. However, it is still largely unknown whether Morinda officinalis extract (MOE) can be used for the treatment of AD. OBJECTIVES: In our study we aimed to determine whether MOE could ameliorate 2,4-dinitrochlorobenzene (DNCB)-induced AD and elucidate molecular mechanisms. METHODS: We established an AD mouse model by using DNCB. Skin pathological analysis and ELISA assay were used to detect the effect of MOE on the inflammation of AD model mouse skin and the expression changes of inflammatory factors, and further functional verification was performed in TNF-α/IFN-γ-induced HaCaT cells. RESULTS: Our in vivo experiments confirmed that MOE remarkably reduced DNCB-induced AD lesions and symptoms, such as epidermal and dermal thickness and mast cell infiltration and inflammatory cytokines secretion in the mice models. In addition, the underlying mechanisms by which MOE ameliorated AD had been uncovered, and we verified that MOE inhibited MALAT1 expression in AD, resulting in attenuated expression of C-C chemokine receptor type 7 (CCR7) regulated by MALAT1-sponge miR-590-5p in a competing endogenous RNA (ceRNA) mechanisms-dependent manner, thereby inhibiting TNF-α/IFN-γ-induced cellular proliferation and inflammation.

Advances in the Functional Nucleic Acid Biosensors for Detection of Lead Ions.

Lead ions (Pb2+) are destructive to the natural environment and public health, so the efficient detection of Pb2+ is particularly important. Although the instrumental analysis methods have high accuracy, they require high cost and precise operation, which limits their wide application. Therefore, many strategies have been extensively studied for detecting Pb2+ by biosensors. Functional nucleic acids have become an efficient tool in this field. This review focuses on the recent biosensors of detecting Pb2+ based on functional nucleic acids from 2010 to 2020, in which DNAzyme, DNA G-quadruplex and aptamer will be introduced. The biosensors are divided into three categories that colorimetric, fluorometric and electrochemical biosensors according to the different reported signals. The action mechanism and detection effect of each biosensor are explained. Finally, the present situation of nucleic acid biosensor for the detection of Pb2+ is summarized and the future research direction is prospected.

[Clinical study of modified Yiyi Baijiang Decoction on psoriasis vulgaris due to dampness-heat accumulation].

The present study observed the clinical effect of modified Yiyi Baijiang Decoction on psoriasis vulgaris and explored its influence on growth factors and inflammatory factors in the serum and skin tissues. A total of 130 patients were randomly divided into control group and experimental group, with 65 cases in each group. The patients in the control group received Acitretin Capsules and Calcipotriol Ointment, and those in the experimental group received modified Yiyi Baijiang Decoction combined with external application for four weeks. The psoriasis area and severity index(PASI), blood vessel count in the superficial dermis(SDBVC), skin thickness(STK), and traditional Chinese medicine(TCM) symptoms were observed before and after treatment. The growth factors [epidermal growth factor(EGF), endothelial cell-specific molecule-1(ESM-1), fibroblast growth factor-23(FGF-23), and transforming growth factor-ß1(TGF-ß1)] and inflammatory factors [nuclear factor-κB(NF-κB), prealbumin(PA), CC chemokine ligand 20(CCL20), and procalcitonin(PCT)] in the serum and skin tissues were detected. The total effective rate was 98.5% in the experimental group, higher than that 83.1% in the control group(P<0.05). Compared with the control group after treatment, the experimental group showed decreased PASI, SDBVC, STK, TCM symptoms, ESM-1, FGF-23, TGF-ß1, NF-κB, CCL20, and PCT(P<0.05), and increased EGF and PA(P<0.05). The incidence of adverse events was 1.5% in the experimental group, lower than that 21.5% in the control group(P<0.05). The results showed that modified Yiyi Baijiang Decoction could effectively relieve skin lesions in patients with psoriasis vulgaris and improve the growth factors and inflammatory factors in the serum and skin lesions, with high safety.

A cysteine and Hg2+ detection method based on transformation supramolecular assembly of cyanine dye by AGRO100.

ETC (3,3'-di(3-sulfopropyl)-4,5,4',5'-dibenzo-9-ethylthiacarbocyanine triethylammonium salt), as a derivative of thiazole, is capable of forming various aggregates by the short-range noncovalent interaction forces under specific conditions, accompanying with significant absorbance and fluorescence characteristics. In this work, a label-free probe (ETC) for the detection of Cys (Cysteine) and Hg2+ was developed based on transformation between monomers and J-aggregations by AGRO100. AGRO100 can transform between single-stranded DNA and G-quadruplex to realize recognition of Cys and Hg2+ in dual-channel mode. These recognitional signals can be captured by UV-visible absorption spectra and fluorescence spectroscopy. ETC exhibits high sensitivity and selectivity with the detection limit of 0.197 nM in a wide range of 0-15 µM, which can apply of Cys and Hg2+ detection in human serum.

The clinical value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) semi-quantitative parameters in monitoring neoadjuvant chemotherapy response of osteosarcoma.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive technique which could monitor tumor morphology, blood vessel dynamics, and micro-environmental changes. PURPOSE: To evaluate the value of DCE-MRI semi-quantitative parameters in monitoring the neoadjuvant chemotherapy (NAC) response of osteosarcoma. MATERIAL AND METHODS: Twenty-five patients pathologically confirmed as osteosarcoma received four cycles of NAC followed by surgery. All patients underwent conventional and dynamic MRI twice, before starting chemotherapy and before surgical treatment. With a reference standard of histological response (tumor necrosis rate), semi-quantitative parameters were compared between good response group (TNR ≥ 90%) and non-response group (TNR < 90%). The differences between intra- and inter-group parameters before and after NAC were analyzed by Mann-Whitney U test. Receiver operating characteristic (ROC) analysis was generated to assess the parameters' efficacy in predicting the outcome of NAC. RESULTS: The changes were statistically significant on slope, maximum signal intensity (SImax), time to peak (TTP), signal enhanced extent (SEE), peak percent enhancement (PPE), washout rate (WOR), and enhancement rate (ER) in the good response group (P < 0.05), while only SImax and SEE were different in the non-response group after NAC. The changes in Slope, SImax, TTP, SEE, WOR, and ER were markedly different (P < 0.05) between the two groups after NAC. Also, at the threshold values of 3.2%/s, 175 s, and 5.4% (slope, TTP, and ER), the sensitivity and specificity for predicting good response to chemotherapy were 83.3% and 92.3%, 91.7% and 69.2%, 84.6% and 75.0%, respectively. CONCLUSION: Slope, TTP, and ER values could be used to evaluate and predict the response to NAC in osteosarcoma.

Research progress in application of big data and artificial intelligence technology in trauma treatment / 中华创伤杂志

Trauma has the characteristics of complex disease, high disability rate and fatality rate, which adds difficulty to treatment. Due to the limitation of medical conditions and untimely allocation of resources, the current trauma treatment modes still have shortcomings such as low first aid efficiency and irregular application, and hence the treatment is facing enormous challenges. In the process of trauma treatment, a large amount of dynamic data that are valuable for disease diagnosis and treatment will be generated. Big data and artificial intelligence technology is an algorithm that can reasonably predict or estimate the given data based on large-scale data collection, and has been applied to trauma treatment modes. The efficient and accurate statistical analysis of big data and innovative medical technology directions such as machine learning, planning and decision-making not only improve the efficiency and safety of trauma treatment, but also reduce the workload of clinicians, making up for the shortcomings of traditional trauma treatment modes. The authors mainly review the application of big data and artificial intelligence technology in pre-hospital first aid and in-hospital diagnosis and treatment for trauma patients, in order to provide a reference for trauma treatment.

An induced-fit de novo initiation mechanism suggested by a pestivirus RNA-dependent RNA polymerase.

Viral RNA-dependent RNA polymerases (RdRPs) play central roles in the genome replication and transcription processes of RNA viruses. RdRPs initiate RNA synthesis either in primer-dependent or de novo mechanism, with the latter often assisted by a 'priming element' (PE) within the RdRP thumb domain. However, RdRP PEs exhibit high-level structural diversity, making it difficult to reconcile their conserved function in de novo initiation. Here we determined a 3.1-Å crystal structure of the Flaviviridae classical swine fever virus (CSFV) RdRP with a relative complete PE. Structure-based mutagenesis in combination with enzymology data further highlights the importance of a glycine residue (G671) and the participation of residues 665-680 in RdRP initiation. When compared with other representative Flaviviridae RdRPs, CSFV RdRP PE is structurally distinct but consistent in terminal initiation preference. Taken together, our work suggests that a conformational change in CSFV RdRP PE is necessary to fulfill de novo initiation, and similar 'induced-fit' mechanisms may be commonly taken by PE-containing de novo viral RdRPs.

Antioxidant and Cytoprotective Effects of New Diarylheptanoids from Rhynchanthus beesianus.

Rhynchanthus beesianus (Zingiberaceae) has been an important food spice and vegetable in southern China. Fifteen phenolic compounds (1-15) including three new diarylheptanoids, rhynchanines A-C (1-3) and one new phenylpropanoid, 4-O-methylstroside B (9), were isolated from R. beesianus rhizomes. The structures of new compounds were elucidated by comprehensive analyses through NMR, HRMS technique, acid hydrolysis, and Mosher's reaction. Among them, compound 5 is the first isolated natural product and its NMR data are reported. Most of the isolated compounds, especially 3-6 and 8, showed significant antioxidant activities on DPPH, ABTS+ radical scavenging, and FRAP assays. Furthermore, the antioxidant phenolic compounds were evaluated for their cytoprotective capacity against H2O2-induced oxidative stress in HepG-2 cells. Compounds 3 and 5 could significantly inhibit reactive oxygen species production, and compounds 3, 5, and 6 could remarkably prevent the cell apoptosis. Then, the R. beesianus rhizome, which contained phenolic compounds, might serve as a functional food for potential application on preventing oxidative stress-connected diseases.

Variation of representative rainfall time series length for rainwater harvesting modelling in different climatic zones.

Rainwater harvesting systems (RHS) have been increasingly used to mitigate urban water scarcity and flooding problems. Rainfall data with various lengths have been used for RHS modelling. However, short-term rainfall data with inadequate lengths used for the modelling of RHS may lead to considerable errors. In this study, a method that can be used to identify representative length of short-term rainfall data for RHS modelling was proposed and tested in 12 cities located in different climatic zones. The influences of local rainfall characteristics on the variation of representative time series lengths (RTSL) were revealed using linear regression and partial correlation analyses. The results show that RHS with larger storage capacity and located in more humid cities can provide higher water saving efficiency and reliability. Rainfall time series length has significant influence on the modelling results of RHS. The RTSL for the 12 cities vary from 6 to 21 years. The RTSL for the 12 cities are non-significantly correlated with mean annual rainfall (R2 = 0.32, n = 12, p > 0.05) and seasonality index (R2 = 0.28, n = 12, p > 0.05), but significantly correlated with variation coefficients of annual rainfall (R2 = 0.76, n = 12, p < 0.05). The partial correlation coefficient between RTSL and the variation coefficients of annual rainfall is 0.878, while the partial correlation coefficients between RTSL and the mean annual rainfall and seasonality index are -0.569 and -0.522, respectively. The results demonstrate the feasibility of using short-term rainfall data with adequate length instead of long-term rainfall data for RHS modelling and also provide insights into the variation of RTSL in different climatic zones.

Risk of venous and arterial thromboembolic events associated with tyrosine kinase inhibitors in advanced thyroid cancer: a meta-analysis and systematic review.

Aims: To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs) associated with tyrosine kinase inhibitors (TKIs) in advanced thyroid cancer patients. Materials and Methods: We comprehensively searched EMBASE, Pubmed, and Cochrane Library for relevant trials. Prospective clinical trials evaluating the role of TKIs alone in advanced thyroid cancer patients were included for analysis. Data on high-grade VTEs and ATEs were extracted. The pooled incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were pooled according to the heterogeneity of included trials. Results: A total of 1,781 patients from 12 trials, including four randomized controlled trials and eight phase II single arm trials, were included for analysis. Our results showed that the overall incidence of high-grade ATEs and VTEs associated with TKIs were 1.4% and 3.3%, and TKIs treatment in advanced TCs patients significantly increased the risk of developing high-grade ATEs (Peto OR 4.72, 95% CI: 1.18-18.95, p = 0.029), but not for high-grade VTEs (Peto OR 1.36, 95% CI: 0.51-3.64, p = 0.54) when compared to placebo. The most common specific causes of ATEs were myocardial infarction (28.6%) and ischemic cerebrovascular events (21.4%), respectively. Conclusions: TKIs treatment in advanced thyroid cancer significantly increases the risk of developing high-grade ATEs but not for VTEs. Clinicians should be cautious about the risk of severe ATEs associated with TKIs to maximize the benefits and minimize the toxicities.

Risk Factors of Deterioration in Quality of Life Scores in Thyroid Cancer Patients After Thyroidectomy.

OBJECTIVE: Despite the expectation of normal life expectancy for thyroid cancer, there are concerns about the decreased quality of life (QoL). The present study investigated the potential risk factors of deterioration in QoL scores in thyroid cancer patients after thyroidectomy. MATERIALS AND METHODS: A total of 286 patients who were diagnosed with thyroid cancer after thyroidectomy were involved in this prospective, single-center, observational study from November 2018 to June 2019. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 was used to assess the QoL 3 months after thyroidectomy. We investigated the effects of demographics (age, gender, education, marital status, area of residence, and annual mean income), tumor characteristics (histology, clinical stage, presence of metastasis, surgery type, and radiotherapy), and neurological deficits induced by recurrent nerve or superior laryngeal injury on QoL. RESULTS: The mean overall QoL in thyroid cancer survivors was 65.93 ±9.00 (on a scale of 0-100, where 100 was the best). Multivariate regression analysis confirmed that clinical stage (P < 0.010), surgery type (P < 0.001), histology (P < 0.001), neurological deficits (P < 0.001), and marital status (P < 0.001) were independent risk factors for decreased QoL 3 months after thyroidectomy. CONCLUSION: Our study indicated that clinical stage, surgery type, histology, neurological deficits, and marital status were independent risk factors for decreased QoL at 3 months after thyroidectomy. Further exploration and validation of these findings in larger prospective studies are warranted.