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Protein tyrosine phosphatase non-receptor type 21 (PTPN21) is a cytosolic protein tyrosine phosphatase that regulates cell growth and invasion. Due to its oncogenic properties, PTPN21 has recently emerged as a potential therapeutic target for cancer. In this study, the three-dimensional structure of the PTPN21 FERM domain was determined at 2.1â Å resolution by X-ray crystallography. The crystal structure showed that this domain harbors canonical FERM folding and consists of three subdomains that are tightly packed via highly conserved intramolecular hydrophobic interactions. Consistent with this, the PTPN21 FERM domain shares high structural homology with several other FERM domains. Moreover, structural superimposition demonstrated two putative protein-binding sites of the PTPN21 FERM domain, which are presumed to be associated with interaction with its binding partner, kinesin family member 1C. Thus, these data suggest that the FERM domain of PTPN21 serves as a module that mediates protein-protein interaction, like other FERM domains.
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Modelos Moleculares , Humanos , Cristalografia por Raios X , Ligação Proteica , Sítios de Ligação , Sequência de Aminoácidos , Domínios Proteicos , Proteínas Tirosina Fosfatases não Receptoras/química , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/genética , Interações Hidrofóbicas e Hidrofílicas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
BACKGROUND: Fluid overload is an independent risk factor of mortality in patients with acute kidney injury (AKI) receiving continuous kidney replacement therapy (CKRT). However, the association between fluid status, as assessed by bioelectrical impedance analysis (BIA) or lung ultrasound, and survival in patients with AKI requiring CKRT has not been established. METHODS: We analyzed 36 participants with sepsis-associated AKI who received CKRT at a tertiary hospital. The main exposures were volume surrogates: 1) overhydration normalized by extracellular water (OH/ECW, L/L) assessed by BIA, 2) the number of B-lines measured by lung ultrasound, and 3) weight change ([body weight at CKRT initiation - body weight at admission] × 100/body weight at admission). The primary outcome was the 28-day mortality. RESULTS: Seventeen participants (47.2%) died within 28 days. There were no significant correlations between OH/ECW and weight change (R2 = 0.040, p = 0.24), number of B-lines and OH/ECW (R2 = 0.056, p = 0.16), or weight change and number of B-lines (R2 = 0.014, p = 0.49). Kaplan-Meier analyses revealed that patients in the highest tertile of OH/ECW showed a significantly lower cumulative 28-day survival probability than the others (the lowest + middle tertiles). The survival probability of participants in the highest tertile of the number of B-lines or weight change did not differ from that of their counterparts. In a multivariate Cox proportional hazard model, the hazard ratio for the highest tertile of OH/ECW was 3.83 (95% confidence interval, 1.04-14.03). CONCLUSION: Volume overload assessed using BIA (OH/ECW) was associated with the 28-day survival rate in patients with sepsis-associated AKI who received CKRT.
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The activation or inactivation of B-cell lymphoma-2 (Bcl-2) antagonist/killer (Bak) is critical for controlling mitochondrial outer membrane permeabilization-dependent apoptosis. Its pro-apoptotic activity is controlled by intermolecular interactions with the Bcl-2 homology 3 (BH3) domain, which is accommodated in the hydrophobic pocket of Bak. Bcl-2-interacting protein 5 (Bnip5) is a noncanonical BH3 domain-containing protein that interacts with Bak. Bnip5 is characterized by its controversial effects on the regulation of the pro-apoptotic activity of Bak. In the present study, we determined the crystal structure of Bak bound to Bnip5 BH3. The intermolecular association appeared to be typical at first glance, but we found that it is maintained by tight hydrophobic interactions together with hydrogen/ionic bonds, which accounts for their high binding affinity with a dissociation constant of 775 nM. Structural analysis of the complex showed that Bnip5 interacts with Bak in a manner similar to that of the Bak-activating pro-apoptotic factor peroxisomal testis-enriched protein 1, particularly in the destabilization of the intramolecular electrostatic network of Bak. Our structure is considered to reflect the initial point of drastic and consecutive conformational and stoichiometric changes in Bak induced by Bnip5 BH3, which helps in explaining the effects of Bnip5 in regulating Bak-mediated apoptosis.
Assuntos
Proteínas Proto-Oncogênicas c-bcl-2 , Proteína Killer-Antagonista Homóloga a bcl-2 , Proteínas Proto-Oncogênicas c-bcl-2/química , Proteína Killer-Antagonista Homóloga a bcl-2/química , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Domínios Proteicos , Proteína bcl-X/metabolismo , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Apoptose/fisiologiaRESUMO
The N-end rule pathway is a proteolytic system involving the destabilization of N-terminal amino acids, known as N-degrons, which are recognized by N-recognins. Dysregulation of the N-end rule pathway results in the accumulation of undesired proteins, causing various diseases. The E3 ligases of the UBR subfamily recognize and degrade N-degrons through the ubiquitin-proteasome system. Herein, we investigated UBR4, which has a distinct mechanism for recognizing type-2 N-degrons. Structural analysis revealed that the UBR box of UBR4 differs from other UBR boxes in the N-degron binding sites. It recognizes type-2 N-terminal amino acids containing an aromatic ring and type-1 N-terminal arginine through two phenylalanines on its hydrophobic surface. We also characterized the binding mechanism for the second ligand residue. This is the report on the structural basis underlying the recognition of type-2 N-degrons by the UBR box with implications for understanding the N-end rule pathway.
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Ubiquitina-Proteína Ligases , Ubiquitina , Ubiquitina-Proteína Ligases/metabolismo , Proteólise , Ubiquitina/metabolismo , Ligação Proteica , Aminoácidos/metabolismoRESUMO
Human papillomaviruses (HPVs) can increase the proliferation of infected cells during HPV-driven abnormalities, such as cervical cancer or benign warts. To date, more than 200 HPV genotypes have been identified, most of which are classified into three major genera: Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus. HPV genomes commonly encode two structural (L1 and L2) and seven functional (E1, E2, E4-E7, and E8) proteins. L2, the minor structural protein of HPVs, not only serves as a viral capsid component but also interacts with various human proteins during viral infection. A recent report revealed that L2 of HPV16 recruits polo-like kinase 1 (Plk1), a master regulator of eukaryotic mitosis and cell cycle progression, for the delivery of viral DNA to mitotic chromatin during HPV16 infection. In this study, we verified the direct and potent interactions between the polo-box domain (PBD) of Plk1 and PBD-binding motif (S-S-pT-P)-containing phosphopeptides derived from L2 of HPV16/HPV18 (high-risk alphapapillomaviruses), HPV5b (low-risk betapapillomavirus), and HPV4 (low-risk gammapapillomavirus). Subsequent structural determination of the Plk1 PBD bound to the HPV18 or HPV4 L2-derived phosphopeptide demonstrated that they interact with each other in a canonical manner, in which electrostatic interactions and hydrogen bonds play key roles in sustaining the complex. Therefore, our structural and biochemical data imply that Plk1 is a broad binding target of L2 of various HPV genotypes belonging to the Alpha-, Beta-, and Gammapapillomavirus genera.
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Papillomavirus Humano , Infecções por Papillomavirus , Humanos , Proteínas do Capsídeo/genética , Fosfopeptídeos/química , Fosfopeptídeos/metabolismo , Quinase 1 Polo-LikeRESUMO
Proper organization of intracellular assemblies is fundamental for efficient promotion of biochemical processes and optimal assembly functionality. Although advances in imaging technologies have shed light on how the centrosome is organized, how its constituent proteins are coherently architected to elicit downstream events remains poorly understood. Using multidisciplinary approaches, we showed that two long coiled-coil proteins, Cep63 and Cep152, form a heterotetrameric building block that undergoes a stepwise formation into higher molecular weight complexes, ultimately generating a cylindrical architecture around a centriole. Mutants defective in Cep63â¢Cep152 heterotetramer formation displayed crippled pericentriolar Cep152 organization, polo-like kinase 4 (Plk4) relocalization to the procentriole assembly site, and Plk4-mediated centriole duplication. Given that the organization of pericentriolar materials (PCM) is evolutionarily conserved, this work could serve as a model for investigating the structure and function of PCM in other species, while offering a new direction in probing the organizational defects of PCM-related human diseases.
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Centríolos , Centrossomo , Proteínas Serina-Treonina Quinases , Humanos , Ciclo Celular , Peso Molecular , Domínios Proteicos , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
Bak is a critical executor of apoptosis belonging to the Bcl-2 protein family. Bak contains a hydrophobic groove where the BH3 domain of proapoptotic Bcl-2 family members can be accommodated, which initiates its activation. Once activated, Bak undergoes a conformational change to oligomerize, which leads to mitochondrial destabilization and the release of cytochrome c into the cytosol and eventual apoptotic cell death. In this study, we investigated the molecular aspects and functional consequences of the interaction between Bak and peroxisomal testis-specific 1 (Pxt1), a noncanonical BH3-only protein exclusively expressed in the testis. Together with various biochemical approaches, this interaction was verified and analyzed at the atomic level by determining the crystal structure of the Bak-Pxt1 BH3 complex. In-depth biochemical and cellular analyses demonstrated that Pxt1 functions as a Bak-activating proapoptotic factor, and its BH3 domain, which mediates direct intermolecular interaction with Bak, plays a critical role in triggering apoptosis. Therefore, this study provides a molecular basis for the Pxt1-mediated novel pathway for the activation of apoptosis and expands our understanding of the cell death signaling coordinated by diverse BH3 domain-containing proteins.
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Proteínas Proto-Oncogênicas c-bcl-2 , Humanos , Masculino , Apoptose/fisiologia , Proteína X Associada a bcl-2 , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Proteínas de Transporte/metabolismo , Mitocôndrias/metabolismoRESUMO
The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format.
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This long-term, retrospective, single-center study evaluated real-world clinical outcomes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma using different therapeutic modalities and analyzed factors affecting survival outcomes and long-term prognosis. We enrolled 203 patients with pathologically confirmed low-grade gastric MALT lymphoma and examined their treatment responses. Helicobacter pylori eradication was performed in all patients with H. pylori infection (HPI) and localized stage gastric MALT lymphoma. All patients underwent pre-treatment and physical evaluations, with complete blood count, biochemistry panel, and staging workup. Among 144 HPI-positive patients with stage I or II1-2 disease who underwent H. pylori eradication, 112 (77.8%) achieved complete remission (CR). All HPI-negative patients who received first-line radiotherapy achieved CR (100%), but only 22 of 27 first-line chemotherapy-treated patients achieved CR (81.5%). Lesions in the proximal upper-third or in multiple locations and an invasion depth to the submucosa or deeper were associated with poor response to eradication, and HPI negativity was significantly correlated with poor progression-free survival. HPI eradication treatment should be the first-line treatment for patients with localized stage HPI-positive gastric MALT lymphoma. The "watch-and-wait" strategy should be adopted for delayed responders. We suggest radiotherapy for patients with a localized HPI-negative status or when eradication has failed.
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Infecções por Helicobacter , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B , Neoplasias Gástricas , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Estudos Retrospectivos , Infecções por Helicobacter/complicações , Prognóstico , Neoplasias Gástricas/patologia , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVE: The objective of this study was to provide preliminary data for improving the health-related quality of life of long-term intensive care unit survivors by identifying the relationship between health-related quality of life and post-intensive care syndrome. METHODS: Using a descriptive correlation research design, data from patients who visited the outpatient department for continuous treatment after discharge from the intensive care unit were analysed. Post-intensive care syndrome was measured by physical, cognitive, and mental problems. Data were collected from 1st August to 31st December, 2019, and 121 intensive care unit survivors participated in the study. RESULTS: Health-related quality of life showed a negative correlation with physical, mental, and cognitive problems. The factors associated with health-related quality of life were physical and mental problems, education level, sedatives and neuromuscular relaxants, and marital status. CONCLUSIONS: To improve the health-related quality of life of intensive care unit survivors, post-intensive care syndrome prevention is important, and a systematic strategy is required through a long-term longitudinal trace study. In addition, intensive care unit nurses and other healthcare professionals need to provide early interventions to reduce post-intensive care syndrome.
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Unidades de Terapia Intensiva , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Estado Terminal/psicologia , Sobreviventes/psicologiaRESUMO
Antiapoptotic B-cell lymphoma-2 (Bcl-2) proteins suppress apoptosis by interacting with proapoptotic regulators. They commonly contain a hydrophobic groove where the Bcl-2 homology 3 (BH3) domain of Bcl-2 family members or BH3 domain-containing non-Bcl-2 family proteins can be accommodated. Peroxisomal testis-specific 1 (Pxt1) was previously identified as a male germ cell-specific protein whose overexpression causes germ cell apoptosis and infertility in male mice. Sequence and biochemical analyses also showed that human Pxt1, which is composed of 134 amino acids and is longer than mouse Pxt1 consisting of only 51 amino acids, has a BH3 domain that interacts with antiapoptotic Bcl-2 proteins, including Bcl-2 and Bcl-xL. In this study, we determined the crystal structure of Bcl-xL bound to the human Pxt1 BH3 domain. The five BH3 consensus residues are well conserved in the human Pxt1 BH3 domain and make a critical contribution to the complex formation in a canonical manner. Structural and biochemical analyses also demonstrated that Bcl-xL interacts with the BH3 domain of human Pxt1 but not with that of mouse Pxt1, and that residues 76-83 of human Pxt1, absent in mouse Pxt1, play a pivotal role in the intermolecular binding to Bcl-xL. While Bcl-xL consistently colocalized with human Pxt1 in mitochondria, it did not do so with mouse Pxt1, when expressed in HeLa cells. Collectively, these data verified that human and mouse Pxt1 differ in their binding ability to the antiapoptotic regulator Bcl-xL, which might affect their functionality in controlling apoptosis.
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Proteínas Reguladoras de Apoptose , Testículo , Sequência de Aminoácidos , Aminoácidos/metabolismo , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Células HeLa , Humanos , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Testículo/metabolismo , Proteína bcl-X/metabolismoRESUMO
BACKGROUND: Accurate staging for depth of invasion (T stage) of early gastric cancer is critical for determining the treatment modality. Endoscopic ultrasonography is a reliable method for assessing the T stage. However, its diagnostic accuracy varies. The aim of this study is to investigate clinicopathologic factors affecting the diagnostic accuracy of endoscopic ultrasonography in early gastric cancer. METHODS: Patients with early gastric cancer who had undergone endoscopic resection or gastrectomy were included. The diagnostic accuracy of endoscopic ultrasonography was evaluated by comparing the T stage by endoscopic ultrasonography with histopathology of the resected specimen. Subgroup analysis was performed according to the endoscopic resection criteria. RESULTS: A total of 223 early gastric cancer lesions were included. The overall accuracy of endoscopic ultrasonography for T staging was 66.4%. The diagnostic accuracy for lesions ≤2 cm was significantly higher than for those of 2-3 cm (odds ratio 3.59) or those >3 cm (odds ratio 5.47). The diagnostic accuracy was significantly decreased in lesions with ulceration (odds ratio 2.62) or non-flat morphology (odds ratio 2.94). The accuracy of endoscopic ultrasonography for lesions corresponding to the absolute endoscopic resection criteria was significantly higher than for those corresponding to the expanded criteria (97.3% vs 71.9%, P = .002). Of the tumors that were overestimated by endoscopic ultrasonography treated with gastrectomy, 93.3% corresponded to the expanded criteria. CONCLUSION: Endoscopic ultrasonography had poor accuracy in early gastric cancer lesions larger than 2 cm, those with ulceration, and those with non-flat morphology, that is, lesions corresponding to the expanded criteria were more frequently overstaged by endoscopic ultrasonography. Such early gastric cancers should be carefully considered when staging by endoscopic ultrasonography before gastrectomy.
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Neoplasias Gástricas , Detecção Precoce de Câncer , Endossonografia/métodos , Gastrectomia , Mucosa Gástrica/patologia , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Úlcera/patologiaRESUMO
OBJECTIVE: Automated registration algorithms for a pair of 2D X-ray mammographic images taken from two standard imaging angles, namely, the craniocaudal (CC) and the mediolateral oblique (MLO) views, are developed. METHODS: A fully convolutional neural network, a type of convolutional neural network (CNN), is employed to generate a pixel-level deformation field, which provides a mapping between masses in the two views. Novel distance-based regularization is employed, which contributes significantly to the performance. RESULTS: The developed techniques are tested using real 2D mammographic images, slices from real 3D mammographic images, and synthetic mammographic images. Architectural variations of the neural network are investigated and the performance is characterized from various aspects including image resolution, breast density, lesion size, lesion subtlety, and lesion Breast Imaging-Reporting and Data System (BI-RADS) category. Our network outperformed the state-of-the-art CNN-based and non-CNN-based registration techniques, and showed robust performance across various tissue/lesion characteristics. CONCLUSION: The proposed methods provide a useful automated tool for co-locating lesions between the CC and MLO views even in challenging cases. SIGNIFICANCE: Our methods can aid clinicians to establish lesion correspondence quickly and accurately in the dual-view X-ray mammography, improving diagnostic capability.
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Mamografia , Redes Neurais de Computação , Raios X , Mamografia/métodos , AlgoritmosRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high mortality and infectivity rates in humans since its emergence. Analysis using high-accuracy real-time polymerase chain reaction (PCR) is recommended for the detection of general respiratory viruses including SARS-CoV-2, but it takes a long time (e.g. ~ 6 h); moreover, on-site diagnosis is difficult owing to the need for skilled technicians and advanced laboratory facilities. Currently, the importance of point-of-care testing (POCT) is being emphasized for the rapid detection of SARS-CoV-2. Here, we developed a multiplex real-time reverse transcription PCR (rRT-PCR) analysis that not only detects SARS-CoV-2 but also D614G strains with higher contagiousness than wild types among SARS-CoV-2 mutants using probe-based rRT-PCR. Moreover, this method was applied to portable PCR equipment capable of POCT to confirm high detection sensitivity and specificity. Multiple assays were possible with fluorescence labeling of individual probes. Furthermore, using a microfluidic chip-based point-of-care testing rRT-PCR platform, detection time was reduced by more than half compared with the commonly used detection system. This demonstrates that our assay has 100% of high sensitivity and specificity and could thus aid in the rapid and simple screening of SARS-CoV-2 carrying the mutation. We present a rapid detection method for mutations in SARS-CoV-2.
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COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , COVID-19/diagnóstico , Humanos , Mutação , Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase em Tempo Real/métodos , SARS-CoV-2/genética , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
High-risk genotypes of human papillomaviruses (HPVs) are directly implicated in various abnormalities associated with cellular hyperproliferation, including cervical cancer. E6 is one of two oncoproteins encoded in the HPV genome, which recruits diverse PSD-95/Dlg/ZO-1 (PDZ) domain-containing human proteins through its C-terminal PDZ-binding motif (PBM) to be degraded by means of the proteasome pathway. Among the three PDZ domain-containing protein tyrosine phosphatases, protein tyrosine phosphatase non-receptor type 3 (PTPN3) and PTPN13 were identified to be recognized by HPV E6 in a PBM-dependent manner. However, whether HPV E6 associates with PTPN4, which also has a PDZ domain and functions as an apoptosis regulator, remains undetermined. Herein, we present structural and biochemical evidence demonstrating the direct interaction between the PBM of HPV16 E6 and the PDZ domain of human PTPN4 for the first time. X-ray crystallographic structure determination and binding measurements using isothermal titration calorimetry demonstrated that hydrophobic interactions in which Leu158 of HPV16 E6 plays a key role and a network of intermolecular hydrogen bonds sustain the complex formation between PTPN4 PDZ and the PBM of HPV16 E6. In addition, it was verified that the corresponding motifs from several other high-risk HPV genotypes, including HPV18, HPV31, HPV33, and HPV45, bind to PTPN4 PDZ with comparable affinities, suggesting that PTPN4 is a common target of various pathogenic HPV genotypes.
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Alphapapillomavirus , Proteínas Oncogênicas Virais , Papillomaviridae , Proteína Tirosina Fosfatase não Receptora Tipo 4 , Proteínas Repressoras , Alphapapillomavirus/química , Alphapapillomavirus/metabolismo , Humanos , Proteínas Oncogênicas Virais/química , Proteínas Oncogênicas Virais/metabolismo , Domínios PDZ , Papillomaviridae/metabolismo , Ligação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 4/química , Proteína Tirosina Fosfatase não Receptora Tipo 4/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/metabolismoRESUMO
Background/Aims: There have been few studies regarding the prognosis of intestinal Behçet's disease (iBD) patients according to consensus-based diagnostic categories, which reflects the typicality of intestinal ulcers, the presence of oral ulcers, and the accompanying systemic manifestations. Methods: The medical records of patients who had ileocolonic ulcers with a clinical impression of iBD were reviewed. The patients were categorized according to the diagnostic algorithm at the time of diagnosis. Adverse events were defined as major surgery or admission related to iBD deterioration. Results: A total of 163 patients were included in the study. The male-to-female ratio was 1:1.2, and the mean age at the time of diagnosis was 48.9±15.9 years. The numbers of patients who met the definite, probable, suspected, and nondiagnostic iBD criteria were 19 (11.7%), 61 (37.4%), 38 (23.3%), and 45 (27.6%), respectively. The event-free survival of patients with definite, probable, and suspected iBD was significantly shorter than that of patients with nondiagnostic iBD (p=0.026), while there was no significant difference among the definite iBD, probable iBD, and suspected iBD groups (p=0.596). After excluding patients with nondiagnostic iBD, multivariate analysis showed that anemia, fever, colonic involvement other than the ileocecum, and accompanying hematologic disorders at the time of diagnosis were significantly associated with the development of adverse events. Conclusions: The clinical course of patients with definite, probable, and suspected iBD is distinguished from that of patients with nondiagnostic iBD, but patients with definite, probable, and suspected iBD share similar clinical courses.
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Síndrome de Behçet , Enteropatias , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Consenso , Feminino , Humanos , Enteropatias/complicações , Enteropatias/diagnóstico , Intestinos , Masculino , ÚlceraRESUMO
BACKGROUND AND AIMS: Sessile serrated lesions (SSLs) are more prone to incomplete resection than conventional adenomas. This study evaluated whether circumferential submucosal incision prior to endoscopic mucosal resection (CSI-EMR) can increase the rate of complete and en bloc resections of colorectal lesions with endoscopic features of SSL. METHODS: Retrospective analyses and propensity score matching were performed for the resection of colorectal lesions ≥ 10 mm with endoscopic features of SSL. RESULTS: After 1:1 ratio matching, 127 lesions in the CSI-EMR group and 127 in the EMR group were selected for analysis. The median size of the lesions was 15 mm (IQR 12-16) in both groups. There was no significant difference in either the complete resection rate or en bloc resection rate between CSI-EMR and EMR groups (96.9% vs. 92.9%, P = 0.155; 92.1% vs. 89.0%, P = 0.391). By contrast, the R0 resection rate was significantly higher in the CSI-EMR group than in the EMR group (89.8% vs. 59.8%, P < 0.001). The median procedure time was significantly longer in the CSI-EMR group than in the EMR group (6.28 min vs. 2.55 min, P < 0.001), whereas there was no significant difference between the two groups in the incidence of adverse events or recurrence rate. Multivariate analysis showed that CSI-EMR was the only factor significantly associated with R0 resection (P < 0.001). CONCLUSIONS: For colorectal lesions with endoscopic features of SSL, CSI-EMR does not increase the complete or en bloc resection rate, but does increase the R0 resection rate. The procedure time is longer for CSI-EMR than EMR. The association of CSI-EMR with R0 resection and non-recurrence should be further evaluated.
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Adenoma , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Adenoma/patologia , Adenoma/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Over the past 6 years, acute respiratory infections have constituted an average of more than 70,000 cases in South Korea. It results in a high mortality rate in infants and the elderly with weak immunity. There are several types of respiratory viruses that invade the human respiratory tract and cause infectious disease. Reverse transcription PCR (RT-PCR) is mainly used for respiratory virus detection owing to its high sensitivity and reproducibility. In response, a multiplex real-time RT-PCR (rRT-PCR) assay was developed for the detection of influenza A and B viruses, parainfluenza viruses 1-4 (PIV1-4), human metapneumovirus, adenovirus, human rhinovirus, respiratory syncytial virus (RSV), and SARS-CoV-2. Detection ability of RT-PCR assay was confirmed by applying it to a portable device capable of point-of-care testing (POCT). Amplicons were synthesized using primer pairs and probe sets designed for each target virus, and a standard curve was constructed to confirm the limit of detection. An experiment using nasopharyngeal swab samples was conducted to understand the field applicability of the rRT-PCR assay. Detection was confirmed in most samples. This study demonstrated that rapid and accurate detection results can be obtained using the multiplex rRT-PCR based POC test, and that it is possible to detect 14 types of respiratory viruses that are generally difficult to distinguish at the same time, enabling timely treatment. Furthermore, we expect that the portable PCR device can significantly reduce the processing procedure of clinical samples before testing, which is the main disadvantage of common RT-PCR tests and can help reduce costs.