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1.
J Agric Food Chem ; 68(20): 5732-5740, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32357302

RESUMO

Carbon dioxide (CO2) microbubbles can selectively enrich organic solutes from sea spray aerosols. Common bubbling extractions are normally followed by off-line separation/detection through methods such as mass spectrometry, chromatography, and spectroscopy. However, it is necessary to establish extractions with online separation and identification systems to improve efficiency and minimize sample loss. In this study, CO2 is used to form microbubbles in the sample solution, and trace analytes in the solution are transported to the gas phase by bubble bursting. Analytes at the liquid-gas interface are directly released into the trapping device, followed by thermal desorption for gas chromatography-mass spectrometry. For polycyclic aromatic hydrocarbons, the dependence of the extraction efficiency on various parameters has been analyzed. The method reported here provides high efficiency and minimizes the loss of trace volatiles with a better signal strength and signal-to-noise ratio than other gases. These features make the proposed method a rapid method to detect and quantify volatile/semivolatile analytes in complex liquid matrices. In addition to the preconcentration of organics, metal ions, and inorganic anions, a noticeable decrease of metal-organic compounds in the aqueous solution was shown for the first time. We finally propose a simple model of chemical partitioning in CO2 bubbling extraction of liquid samples for guiding online monitoring of trace analytes in real-world samples.

2.
Biomed Res Int ; 2020: 6061894, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32337261

RESUMO

Background: Posterior capsule opacification (PCO), a complication of extracapsular lens extraction surgery that causes visual impairment, is characterized by aberrant proliferation and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). Curcumin, exerting inhibitive effects on cell proliferation and EMT in cancer, serves as a possible antidote towards PCO. Methods: Cellular proliferation of LECs after treatment of curcumin was measured with MTT assay and flow cytometry. The transcriptional and expressional levels of proteins related to proliferation and EMT of LECs were quantified by western blotting and real-time PCR. Results: Curcumin was found to suppress the proliferation of LECs by inducing G2/M arrest via possible inhibition of cell cycle-related proteins including CDK1, cyclin B1, and CDC25C. It had also inactivated proliferation pathways involving ERK1/2 and Akt pathways in LECs. On the other hand, curcumin downregulated the EMT of LECs through blocking the TGF-ß/Smad pathway and interfering Notch pathway which play important roles in PCO. Conclusions: This study shows that curcumin could suppress the proliferation and EMT in LECs, and it might be a potential therapeutic protection against visual loss induced by PCO.

3.
Lung Cancer ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32336530

RESUMO

OBJECTIVES: To describe the treatment patterns and outcomes of Chinese non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in real-world as EGFR ex20ins consist of a diverse group of mutations with limited information on the clinical outcome of these patients treated with chemotherapy or EGFR tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: Real-world treatment outcomes of Chinese NSCLC patients harboring EGFR ex20ins were retrospectively analyzed based on medical records at different institutions and detailed web-based patient questionnaires. RESULTS: Between March 17, 2018 and December 20, 2018, 165 advanced EGFR ex20ins NSCLC patients treated in 99 hospitals from 26 different regions in China were analyzed. Thirty-nine different molecular variants of EGFR ex20ins were identified with V769_D770insASV being the most common (23.0 %). Central nervous system (CNS) metastasis occurred in 23.0 % of patients at the time of baseline diagnosis. Median progression-free survival (PFS) was significantly longer in patients who received first-line platinum-based chemotherapy (6.4 m; 95 % CI: 5.7-7.1) than all-generation EGFR TKIs (2.9 m; 95 %CI: 1.5-4.3; P < 0.001) or 1st-generation EGFR TKIs (2.0 m; 95 %CI: 0.2-3.8; P < 0.001). Median PFS was numerically longer in patients who received second-line chemotherapy (4.0 m; 95 %CI: 3.2-4.8) than those received second-line EGFR TKIs (2.0 m; 95 %CI: 1.1-2.9; P = 0.342). Patients with CNS metastasis had numerically shorter median PFS than those without CNS metastasis when treated with 1st-line chemotherapy (3.6 m; 95 %CI: 0-8.0 vs. 6.5 m; 95 %CI: 4.9-8.1; P = 0.645) or 1st-line EGFR TKIs (2.0 m; 95 %CI: 0.8-3.2 vs. 2.9 m; 95 %CI: 2.1-3.7; P = 0.058). CONCLUSION: Chemotherapy is superior to current approved EGFR TKIs as 1st- or 2nd-line treatment of EGFR ex20ins mutations. CNS metastasis conferred numerically shorter PFS with chemotherapy or EGFR TKIs treatment. Targeted agent against EGFR ex20ins with CNS activity is urgently needed.

4.
Nanotechnology ; 31(30): 305708, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32259801

RESUMO

Low dimensional superconductors have many unusual properties. When 0-dimensional superconductors reach the nanometer scale, the superconducting energy gap can be enhanced due to the shell effect. At the same time, the single electron Coulomb blockade effect can also be observed on metal nanoparticles if they are weakly coupled to the environment. So, if a superconducting nanoparticle is isolated well from the environment, the superconducting gap and the Coulomb gap would couple together, making the tunneling spectrum more complicated and interesting. Here Sn nanoparticles were deposited on the surface of STO (111). The charging energy of a nanoparticle mainly depends on its size and is comparable to the superconducting gap when the isolated particle is large enough. The superconducting energy gap can be deduced from the coupling tunneling spectrum and the shell effect is observed. The method to deduce the superconducting gap here is simpler than when fit using the Dynes density of states. Owing to the increased superconducting gap and critical field, the studied nanoparticles may find applications in studies of the properties of Majorana fermions.

5.
Microorganisms ; 8(4)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276396

RESUMO

The use of prebiotics to regulate gut microbiota is a promising strategy to improve gut health. Pectin (PEC) is a prebiotic carbohydrate that enhances the health of the gut by promoting the growth of beneficial microbes. These microbes produce metabolites that are known to improve mucosal immune responses. This study was conducted to better understand effects of PEC on the microbiome and mucosal immunity in pigs. Pigs were fed two diets, with or without 5% apple PEC, for 72 days. Effects of PEC on the microbiota, cytokine expression, short-chain fatty acids (SCFAs) concentration and barrier function were examined in the ileum and cecum of the pigs. An integrative analysis was used to determine interactions of PEC consumption with bacterial metabolites and microbiome composition and host mucosal responses. Consumption of PEC reduced expression of pro-inflammatory cytokines such as IFN-γ, IL-6, IL-8, IL-12 and IL-18, and the activation of the pro-inflammatory NF-κB signaling cascade. Expression of MUC2 and TFF and the sIgA content was upregulated in the mucosa of PEC-fed pigs. Network analysis revealed that PEC induced significant interactions between microbiome composition in the ileum and cecum on mucosal immune pathways. PEC-induced changes in bacterial genera and fermentation metabolites, such as Akkermansia, Faecalibacterium, Oscillibacter, Lawsonia and butyrate, correlated with the differentially expressed genes and cytokines in the mucosa. In summary, the results demonstrate the anti-inflammatory properties of PEC on mucosal immune status in the ileum and cecum effected through modulation of the host microbiome.

7.
Am J Pathol ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32201259

RESUMO

Hepatocellular carcinoma (HCC) is the most common form of liver tumors. Although HCC is associated with chronic viral infections, alcoholic cirrhosis, and nonalcoholic fatty liver disease, genetic factors that contribute to the HCC risk remain unknown. The BRCA2 DNA repair associated (BRCA2) and cyclin-dependent kinase inhibitor 1A (CDKN1A) interacting protein, known as BCCIP, are essential for cell viability and maintenance of genomic stability. In this study, we established a new genetically engineered mouse model with Bccip deficiency. Mosaic or heterozygous Bccip deletion conferred an increased risk of spontaneous liver tumorigenesis and B-cell lymphoma development at old age. These abnormalities are accompanied with chronic inflammation, histologic features of nonalcoholic steatohepatitis, keratin and ubiquitin aggregates within cytoplasmic Mallory-Denk bodies, and changes of the intracellular distribution of high-mobility group box 1 protein. Our study suggests BCCIP dysregulation as a risk factor for HCC and offers a novel mouse model for future investigations of nonviral or nonalcoholic causes of HCC development.

8.
J Med Chem ; 63(8): 4155-4170, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202782

RESUMO

Pan-genotype NS5A inhibitors underpin hugely successful hepatitis C virus (HCV) therapy. The discovery of GSK2818713 (13), a nonstructural protein 5A (NS5A) HCV inhibitor characterized by a significantly improved genotype coverage relative to first-generation NS5A inhibitor daclatasvir (DCV), is detailed herein. The SAR analysis revealed cooperative potency effects of the biphenylene, bicyclic pyrrolidine (Aoc), and methyl-threonine structural motifs. Relative to DCV, 13 improved activity against genotype 1a (gt1a) and gt1b NS5A variants as well as HCV chimeric replicons containing NS5A fragments from genotypes 2-6. Long-term treatment of subgenomic replicons with 13 potently and durably decreased HCV RNA levels for gt1a, gt2a, and gt3a. These properties, suitable pharmacokinetics, and the lack of cross-resistance resulted in the selection of 13 as a preclinical candidate.

10.
J Agric Food Chem ; 68(13): 3963-3975, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32162923

RESUMO

Gut microbes play significant roles in colitis development. The current study was aimed to uncover the preventive effects of lycopene (LYC), a functional carotenoid component, on colitis and the accompanied behavior disorders. The current study demonstrated that LYC treatment (50 mg/kg body weight/day) for 40 days prevented the dextran sulfate sodium (DSS)-induced gut barrier damages and inflammatory responses in male mice. LYC improved DSS-induced depression and anxiety-like behavioral disorders by suppressing neuroinflammation and prevented synaptic ultrastructure damages by upregulating the expressions of neurotrophic factor and postsynaptic-density protein. Moreover, LYC reshaped the gut microbiome in colitis mice by decreasing the relative abundance of proteobacteria and increasing the relative abundance of Bifidobacterium and Lactobacillus. LYC also elevated the generation of short-chain fatty acids and inhibited the permeability of lipopolysaccharide in colitis mice. In conclusion, LYC ameliorate DSS-induced colitis and behavioral disorders via mediating microbes-gut-brain axis balance.

11.
J Hazard Mater ; 393: 122390, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32114130

RESUMO

Iron oxide nanoparticles (IONPs), commonly occurring in soils, aquifers and subsurface sediments, may serve as important electron shuttles for the biotransformation of coexisting toxic metals. Here, we explored the impact of different IONPs (low-crystallinity goethite and ferrihydrite, high-crystallinity magnetite and hematite) on the reduction of Cu(II) by Geobacter sulfurreducens and the associated electron shuttle mechanisms. All four IONPs tested can function as electron shuttles to enhance long distance electron transfer from bacteria to Cu(II). Upon IONPs addition, the rate of Cu(II) reduction increased from 14.9 to 65.0-83.8 % in solution after 7 days of incubation. Formation of both Cu(I) and Cu(0) on the iron oxide nanoparticles was revealed by the X-ray absorption near-edge spectroscopy. The IONPs can be utilized as conduits by bacteria to directly transfer electrons and they can also reversibly accept and donate electrons as batteries through a charging-discharging cycle to transfer electron. The latter mechanism (geo-battery) played an important role in all four types of IONPs while the former one (geo-conductor) can only be found in the magnetite and hematite treatments due to the higher crystallinity. Our results shed new light on the biogeochemically mediated electron flux in microbe-IONPs-metal networks under anaerobic iron-reduction conditions.

12.
Anal Bioanal Chem ; 412(12): 2711-2720, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32140733

RESUMO

A simple and sensitive C18 packed ballpoint-electrospray ionization (PBP-ESI) technique was developed for biofluid analysis. In this technique, the configuration of a commercial ballpoint consisting of a hollow chamber, an intermediate socket, and a metal ball was fully exploited. The rear-end hollow chamber was used for loading C18 adsorbent and sample, and the front metal ball served as a spray emitter for online ionization. The good electrical conductivity of the metal body allowed high voltage to be conveniently applied to the ballpoint without inserting the electrode into the solution for electrical connection. Urine sample was directly analyzed with the C18 packed ballpoint; plasma and whole blood samples were premixed with C18 adsorbent before being packed into the ballpoint for detection. As a result of the sample cleanup by C18 adsorbent, the salt matrix in the urine sample as well as the phospholipid and protein matrices in plasma and whole blood samples was significantly reduced. The lower limits of quantitation (LLOQs) for urine, plasma, and whole blood samples reached the subnanogram-per-milliliter level. Graphical abstract.

13.
Vet Res ; 51(1): 26, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093767

RESUMO

Probiotic pretreatment is an effective non-antibiotic strategy for preventing or controlling Salmonella infections. We found that Lactobacillus johnsonii L531, isolated from the colon of a clinically healthy weaned piglet, effectively prevented infection with Salmonella enterica serovar Infantis in a pig model. Newly weaned piglets were intragastrically administered Lactobacillus johnsonii L531 at 1.0 × 1010 CFU/day for 1 week before S. Infantis challenge. Pretreatment with L. johnsonii L531 lessened the severity of diarrhea and ileal inflammation in S. Infantis-infected piglets. Lactobacilli were more abundant in the ileum than jejunum after L. johnsonii L531 pretreatment. Treatment with L. johnsonii L531 reduced the abundance of total bacteria in the ileal mucosa and the production of lipocalin 2 in the jejunum of piglets challenged with Salmonella. Both intestinal morphology and transmission electron microscopy results indicated that L. johnsonii L531 alleviated intestinal tissue damage following S. Infantis challenge, especially in the villus and endoplasmic reticulum (ER). ER stress induced by S. Infantis was attenuated by L. johnsonii L531 treatment. The number of CD4- CCR6+ T cells decreased following S. Infantis challenge, but the percentage of CCR6- IFNγ+ T cells in peripheral blood increased. In intestinal mesenteric lymph nodes, S. Infantis increased the proportion of CCR6+ IFNγ+ T cells, whereas L. johnsonii L531 induced an increase in the proportion of CD4+ CCR6+ T cells in response to S. Infantis infection. Our data thus suggest that L. johnsonii L531 contributes to the maintenance of intestinal homeostasis by modulating T-cell responses and ER stress.

14.
Int J Nanomedicine ; 15: 315-332, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021182

RESUMO

Purpose: The clinical outcome of spinal cord injury is usually poor due to the lack of axonal regeneration and glia scar formation. As one of the most classical supporting cells in neural regeneration, Schwann cells (SCs) provide bioactive substrates for axonal migration and release molecules that regulate axonal growth. However, the effect of SC transplantation is limited by their poor migration capacity in the astrocyte-rich central nervous system. Methods: In this study, we first magnetofected SCs with chondroitinase ABC-polyethylenimine functionalized superparamagnetic iron oxide nanoparticles (ChABC/PEI-SPIONs) to induce overexpression of ChABC for the removal of chondroitin sulfate proteoglycans. These are inhibitory factors and forming a dense scar that acts as a barrier to the regenerating axons. In vitro, we observed the migration of SCs in the region of astrocytes after the application of a stable external magnetic field. Results: We found that magnetofection with ChABC/PEI-SPIONs significantly up-regulated the expression of ChABC in SCs. Under the driven effect of the directional magnetic field (MF), the migration of magnetofected SCs was enhanced in the direction of the magnetic force. The number of SCs with ChABC/PEI-SPIONs migrated and the distance of migration into the astrocyte region was significantly increased. The number of SCs with ChABC/PEI-SPIONs that migrated into the astrocyte region was 11.6- and 4.6-fold higher than those observed for the intact control and non-MF groups, respectively. Furthermore, it was found that SCs with ChABC/PEI-SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF. Conclusion: The mobility of the SCs with ChABC/PEI-SPIONs was enhanced along the axis of MF, holding the potential to promote nerve regeneration by providing a bioactive microenvironment and relieving glial obstruction to axonal regeneration in the treatment of spinal cord injury.


Assuntos
Astrócitos/fisiologia , Condroitina ABC Liase/metabolismo , Nanopartículas de Magnetita/uso terapêutico , Regeneração Nervosa/fisiologia , Células de Schwann/fisiologia , Animais , Astrócitos/citologia , Axônios/efeitos dos fármacos , Movimento Celular , Células Cultivadas , Condroitina ABC Liase/genética , Condroitina ABC Liase/farmacologia , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Feminino , Campos Magnéticos , Nanopartículas de Magnetita/química , Masculino , Regeneração Nervosa/efeitos dos fármacos , Polietilenoimina/química , Ratos , Ratos Sprague-Dawley , Células de Schwann/citologia , Traumatismos da Medula Espinal/terapia
15.
J Med Chem ; 63(7): 3552-3562, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32073266

RESUMO

We report the discovery of a novel indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor class through the affinity selection of a previously unreported indole-based DNA-encoded library (DEL). The DEL exemplar, spiro-chromane 1, had moderate IDO1 potency but high in vivo clearance. Series optimization quickly afforded a potent, low in vivo clearance lead 11. Although amorphous 11 was highly bio-available, crystalline 11 was poorly soluble and suffered disappointingly low bio-availability because of solubility-limited absorption. A prodrug approach was deployed and proved effective in discovering the highly bio-available phosphonooxymethyl 31, which rapidly converted to 11 in vivo. Obtaining crystalline 31 proved problematic, however; thus salt screening was performed in an attempt to circumvent this obstacle and successfully delivered greatly soluble and bio-available crystalline tris-salt 32. IDO1 inhibitor 32 is characterized by a low calculated human dose, best-in-class potential, and an unusual inhibition mode by binding the IDO1 heme-free (apo) form.

16.
Waste Manag ; 105: 268-278, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32088573

RESUMO

In the construction industry, reuse and recycling strategies help reducing waste, saving energy and cutting down emissions by converting construction and demolition (C&D) waste into resources. This study proposes a novel framework to guide the life cycle assessment (LCA) of concrete structures with reuse and recycling strategies. The material flow in recycling strategies is clarified explicitly. A new definition of degradation rate is introduced to set a nonlinear allocation rule for reusable components based on the durability feature of concrete structures. Reusable rate and replacement percentage are adopted to provide a convenient way to adjust the type and level of the strategies. As a result, a unified system boundary and corresponding indicator functions can be established for various strategies, combing the closed-loop analysis and the open-loop analysis. In the case study, design for deconstruction (DfD) and recycled aggregate concrete (RAC) are taken as examples of reuse and recycling strategies, respectively. With the proposed framework, LCA of various strategy combinations are conducted considering the global warming potential (GWP) and abiotic depletion potential (ADP) indicators. Results show that the maximal environmental benefit of DfD is 1.8-2.8 times compared to that of RAC. When adopting DfD and RAC simultaneously, the environmental benefit level of each strategy will decline, whereas the overall benefits will be increased. LCA with the proposed framework avoids some assumptions in conventional LCA and provides more reliable results for various strategy combinations.


Assuntos
Indústria da Construção , Gerenciamento de Resíduos , Materiais de Construção , Aquecimento Global , Reciclagem
17.
Strahlenther Onkol ; 196(4): 405, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32078694

RESUMO

Correction to: Strahlenther Onkol 2019 https://doi.org/10.1007/s00066-019-01539-1 The original version of this article unfortunately contained a mistake. The correct version of the funding information are given ….

18.
J Phys Chem Lett ; : 1255-1260, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31990572

RESUMO

Circularly polarized luminescent (CPL) materials are promising in applications such as 3D displays and quantum communication. Hybrid organic-inorganic copper(I) iodides have been rapidly developed due to their intense photoluminescence and structural diversity; nevertheless, the reported Cu-I clusters rarely show CPL activities. In this study, we introduced chiral organic molecules R/S-methylbenzylammonium (R/S-MBA) into Cu-I inorganic skeletons to achieve chiral tetranuclear (R/S-MBA)4Cu4I4 clusters with intense orange luminescence and CPL activity at room temperature. These enantiomeric (R/S-MBA)4Cu4I4 clusters show oppositely signed circular dichroism (CD) signals, which agree well with their simulated electronic CD spectra. The crystallization-induced helical arrangement of (R/S-MBA)4Cu4I4 clusters and their largely distorted polynuclear configuration demonstrate a new platform for the study of chiral-related properties.

19.
FASEB J ; 34(2): 2821-2839, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31908018

RESUMO

Newly weaned piglets challenged with Salmonella infantis were particularly susceptible, whereas oral preadministration of Lactobacillus johnsonii L531 alleviated enteritis and promoted intestinal secretory IgA production. Salmonella infantis-induced activation of NLRC4 and NLRP3 inflammasomes and (nuclear factor kappa B) NF-κB signaling in the small intestine was also inhibited by L. johnsonii L531 pretreatment, thus limiting inflammation. An IPEC-J2 cell model of S. infantis infection yielded similar results. Salmonella infantis infection also resulted in mitochondrial damage and impaired mitophagy in the ileum and IPEC-J2 cells, as demonstrated by immunofluorescence colocalization of mitochondria with microtubule-binding protein light chain 3 (LC3) and high expression of autophagy-related proteins PTEN-induced putative kinase 1 (PINK1), sequestosome 1 (SQSTM1/p62), optineurin (OPTN), and LC3 by Western blotting analysis. However, L. johnsonii L531 pretreatment reduced both the extent of mitochondrial damage and autophagy-related protein expression. Our findings suggest that the amelioration of S. infantis-associated enteritis by L. johnsonii L531 is associated with regulation of NLRC4 and NLRP3 inflammasomes and NF-κB signaling pathway activation and suppression of mitochondrial damage. Amelioration of impaired mitophagy by L. johnsonii L531 could involve eliminating damaged mitochondria and regulating S. infantis-induced activation of the NF-κB-SQSTM1mitophagy signaling pathway in host cells to prevent the further mitochondrial damage and S. infantis dissemination.

20.
Childs Nerv Syst ; 36(1): 219-221, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31410565

RESUMO

INTRODUCTION: Tethered cord syndrome (TCS) is the progressive development of various neuromuscular dysfunctions caused by the traction of the conus medullaris resulting from congenital or acquired causes, which are often accompanied by fecal and/or urinary incontinence and abnormal sensory motor functions of lower limbs. Lower back pain is a common clinical symptom of TCS patients and can be significantly improved by surgical untethering. However, the specific relationship between the increase in lumbosacral angle and TCS has rarely been reported. PATIENT: A case of TCS in an 8-year-old girl is reported. The patient had lower back pain complicated by increased lumbosacral angle for more than 20 days. DIAGNOSES: Physical examination and MRI results showed that the condition of the child has been complicated by TCS. INTERVENTIONS: After additional relevant examination, surgical untethering of the terminal filum was performed under general anesthesia. OUTCOMES: The symptoms of lower back pain disappeared, and the plain radiographs indicated that the lumbosacral angle decreased and lumbar lordosis returned to normal. During the follow-up period of half a year, the child did not experience particular discomfort or asymptomatic aggravation. CONCLUSIONS: For children with low back pain complicated by lumbosacral angle increase, MRI should be performed to exclude TCS. Once the patient has been diagnosed, early surgical treatment should be provided.

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