RESUMO
Since smallpox was eradicated in 1980, the monkeypox virus (MPXV) has emerged as the most threatening orthopoxvirus in the world. In this study, we conducted a comprehensive analysis of the currently published complete genome sequences of the monkeypox virus. The core/variable regions were identified through core-pan analysis of MPXV. Besides single-nucleotide polymorphisms, our study also revealed that specific genes, multi-copy genes, repeat sequences, and recombination fragments are primarily distributed in the variable region. This result suggests that variable regions are not only more susceptible to single-base mutations, but also to events such as gene loss or gain, as well as recombination. Taken together, our results demonstrate the genomic characteristics of the core/variable regions of MPXV, and contribute to our understanding of the evolution of MPXV.
Assuntos
Monkeypox virus , Mpox , Humanos , Monkeypox virus/genética , Genômica , Mutação , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Understanding how function and structure are organized and their coupling with clinical traits in individuals with autism spectrum disorder (ASD) is a primary goal in network neuroscience research for ASD. Atypical brain functional networks and structures in individuals with ASD have been reported, but whether these associations show heterogeneous hierarchy modeling in adolescents and adults with ASD remains to be clarified. In this study, 176 adolescent and 74 adult participants with ASD without medication or comorbidities and sex, age matched healthy controls (HCs) from 19 research groups from the openly shared Autism Brain Imaging Data Exchange II database were included. To investigate the relationship between the functional gradient, structural changes, and clinical symptoms of brain networks in adolescents and adults with ASD, functional gradient and voxel-based morphometry (VBM) analyses based on 1000 parcels defined by Schaefer mapped to Yeo's seven-network atlas were performed. Pearson's correlation was calculated between the gradient scores, gray volume and density, and clinical traits. The subsystem-level analysis showed that the second gradient scores of the default mode networks and frontoparietal network in patients with ASD were relatively compressed compared to adolescent HCs. Adult patients with ASD showed an overall compression gradient of 1 in the ventral attention networks. In addition, the gray density and volumes of the subnetworks showed no significant differences between the ASD and HC groups at the adolescent stage. However, adults with ASD showed decreased gray density in the limbic network. Moreover, numerous functional gradient parameters, but not VBM parameters, in adolescents with ASD were considerably correlated with clinical traits in contrast to those in adults with ASD. Our findings proved that the atypical changes in adolescent ASD mainly involve the brain functional network, while in adult ASD, the changes are more related to brain structure, including gray density and volume. These changes in functional gradients or structures are markedly correlated with clinical traits in patients with ASD. Our study provides a novel understanding of the pathophysiology of the structure-function hierarchy in ASD.
Assuntos
Transtorno do Espectro Autista , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/patologia , Adolescente , Masculino , Feminino , Adulto , Adulto Jovem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/patologia , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Pessoa de Meia-IdadeRESUMO
GOALS: In this study, we conducted this network meta-analysis (based on the ANOVA model) to evaluate the predictive efficacy of each early predictor. BACKGROUND: Persistent organ failure (POF) is one of the determining factors in patients with acute pancreatitis (AP); however, the diagnosis of POF has a long-time lag (>48 h). It is of great clinical significance for the early noninvasive prediction of POF. STUDY: We conducted a comprehensive and systematic search in PubMed, Cochrane library, Embase, and Web of Science to identify relevant clinical trials, case-control studies, or cohort studies, extracted the early indicators of POF in studies, and summarized the predictive efficacy of each indicator through network meta-analysis. The diagnostic odds ratio (DOR) was used to rank the prediction efficiency of each indicator. RESULTS: We identified 23 studies in this network meta-analysis, including 10,393 patients with AP, of which 2014 patients had POF. A total of 10 early prediction indicators were extracted. The mean and 95% CI lower limit of each predictive indicator were greater than 1.0. Albumin had the largest diagnostic odds ratio, followed by high-density lipoprotein-cholesterol (HDL-C), Ranson Score, beside index for severity in acute pancreatitis Score, acute physiology and chronic health evaluation II, C-reactive protein (CRP), Interleukin 6 (IL-6), Interleukin 8 (IL-8), Systemic Inflammatory Response Syndrome (SIRS) and blood urea nitrogen. CONCLUSIONS: Albumin, high-density lipoprotein-cholesterol, Ranson Score, and beside index for severity in acute pancreatitis Score are effective in the early prediction of POF in patients with AP, which can provide evidence for developing effective prediction systems. However, due to the limitations of the extraction method of predictive indicators in this study, some effective indicators may not be included in this meta-analysis.
Assuntos
Pancreatite , Humanos , Pancreatite/diagnóstico , Doença Aguda , Metanálise em Rede , Prognóstico , Estudos Retrospectivos , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Proteína C-Reativa , Lipoproteínas HDL , Colesterol , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Acute pancreatitis is easily confused with abdominal pain symptoms, and it could lead to serious complications for pregnant women and fetus, the mortality was as high as 3.3% and 11.6-18.7%, respectively. However, there is still lack of sensitive laboratory markers for early diagnosis of APIP and authoritative guidelines to guide treatment. OBJECTIVE: The purpose of this study was to explore the risk factors of acute pancreatitis in pregnancy, establish, and evaluate the dynamic prediction model of risk factors in acute pancreatitis in pregnancy patients. STUDY DESIGN: Clinical data of APIP patients and non-pregnant acute pancreases patients who underwent regular antenatal check-ups during the same period were collected. The dataset after propensity matching was randomly divided into training set and verification set at a ratio of 7:3. The model was constructed using Logistic regression, least absolute shrinkage and selection operator regression, R language and other methods. The training set model was used to construct the diagnostic nomogram model and the validation set was used to validate the model. Finally, the accuracy and clinical practicability of the model were evaluated. RESULTS: A total of 111 APIP were included. In all APIP patients, hyperlipidemic pancreatitis was the most important reason. The levels of serum amylase, creatinine, albumin, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein A1 were significantly different between the two groups. The propensity matching method was used to match pregnant pancreatitis patients and pregnant non-pancreatic patients 1:1 according to age and gestational age, and the matching tolerance was 0.02. The multivariate logistic regression analysis of training set showed that diabetes, triglyceride, Body Mass Index, white blood cell, and C-reactive protein were identified and entered the dynamic nomogram. The area under the ROC curve of the training set was 0.942 and in validation set was 0.842. The calibration curve showed good predictive in training set, and the calibration performance in the validation set was acceptable. The calibration curve showed the consistency between the nomogram model and the actual probability. CONCLUSION: The dynamic nomogram model we constructed to predict the risk factors of acute pancreatitis in pregnancy has high accuracy, discrimination, and clinical practicability.
Assuntos
Nomogramas , Pancreatite , Complicações na Gravidez , Pontuação de Propensão , Humanos , Feminino , Gravidez , Pancreatite/diagnóstico , Pancreatite/sangue , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Medição de Risco/métodos , Adulto , Fatores de Risco , Doença Aguda , Estudos RetrospectivosRESUMO
Peroral endoscopic myotomy (POEM) has revolutionized the therapeutic strategy for achalasia with promising results. We conducted this meta-analysis to compare clinical outcomes between Eastern and Western countries. A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library databases to query for studies that assessed the efficacy of POEM for achalasia. All articles published from inception to December 31, 2021 were included. The primary outcome was the pooled clinical success rate. The secondary outcomes included the pooled technical success rate, incidence of adverse events, procedure time and hospital stay. Eighteen Eastern studies involving 5962 patients and 11 Western studies involving 1651 patients were included. The pooled clinical success rate and technical success rate for POEM was equal in the Eastern studies compared to Western studies. The pooled incidence of procedure adverse events for POEM was a little lower in the Eastern studies compared to Western studies (6.6% vs. 8.7%). Similarly, the incidence of reflux-related adverse events was lower in Eastern studies than that in Western studies. The pooled procedure time of POEM was shorter in Eastern studies compared to Western studies (61 minutes vs. 80 minutes), while the length of hospital stay was longer in Eastern studies compared to Western studies (5.8 days vs. 2.4 days). Overall, Eastern countries have the similar POEM outcomes compared to Western countries. However, Eastern countries still need to do more to reduce the length of hospital stay.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Acalasia Esofágica , Miotomia , Humanos , Acalasia Esofágica/cirurgia , Bases de Dados Factuais , Tempo de InternaçãoRESUMO
Long noncoding RNAs (lncRNAs) contribute to esophageal squamous cell carcinoma (ESCC) progression, but the underlying mechanisms remain elusive. In this study, we verified a hitherto uncharacterized hypoxia-responsive lncRNA, G077640, which is upregulated in human ESCC cells and tissues, supporting the proliferation and migration of ESCC cells. Mechanistically, G077640 prevented hypoxia-inducible factor-1α (HIF1α) from being degraded by directly interacting with histone H2AX and further modulated the interaction of HIF1α and H2AX. In addition, G077640 reprogrammed glycolytic metabolism by regulating the expression of glucose transporter 4 (GLUT4), hexokinase 2 (HK2) and pyruvate dehydrogenase kinase 1 (PDK1) for ESCC proliferation and migration. Clinically, G077640 was associated with poor prognosis in ESCC patients. Taken together, our findings identified a hypoxia-responsive lncRNA that contributes to ESCC cells proliferation and migration, and targeting G077640 and its pathway might be a potential therapeutic strategy for ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , RNA Longo não Codificante , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Esofágicas/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linhagem Celular Tumoral , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Hipóxia , Glicólise/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Recent studies have shown that women are underrepresented as authors of medical research and clinical practice guidelines. This study aimed to evaluate gender disparities of authors of major hepatology guidelines. METHODS: We reviewed the hepatology guidelines published by the following major gastroenterology societies from January 2008 to September 2022: the American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), American Association for the Study of Liver Diseases (AASLD), Asian-Pacific Association for the Study of the Liver (APASL), British Society of Gastroenterology (BSG), European Association for the Study of the Liver (EASL) and Korean Association for the Study of the Liver (KASL). We determined the topic and the gender of all authors of each guideline. The numbers of men authors, women authors and total authors were collected. The trends of women first authors, women senior authors and total women authors were assessed. A logistic regression analysis was performed to analyse the relationship between the gender of the first or senior author and related factors. RESULTS: We identified 103 hepatology guidelines published between January 2008 and September 2022 published by the AGA, ACG, AASLD, APASL, BSG, EASL, and KASL. The gender of 1096 of 1100 (99.6%) authors was determined. Therefore, a total of 1096 authors were included: 223 (20.3%) authors were women and 873 (79.7%) authors were men. Women comprised 14.6% of all first authors, and 20.4% of all senior authors were women. Only the AASLD had writing committees comprising more than 30% total women authors. The proportions of women senior authors and total women authors increased significantly during the study period (p < .05). Women first authors and women senior authors were more likely to publish guidelines with more women authors. Women first authors were less likely to be co-authors with men authors. CONCLUSIONS: Over the course of the past decade, the proportion of women authors of major hepatology guidelines has been low; however, this gender gap appears to be closing.
Assuntos
Pesquisa Biomédica , Gastroenterologia , Masculino , Humanos , Feminino , Estados Unidos , Fatores Sexuais , Autoria , FígadoRESUMO
BACKGROUND: Recently, numerous publications on Helicobacter pylori (H. pylori) have been published, but bibliometric analyses on this research field are scarce. To address this gap, we conducted a bibliometric analysis to provide a comprehensive overview and to explore the current research states and hotspots in this field. MATERIALS AND METHODS: Publications on H. pylori from 2002 to 2021 were retrieved from the Web of Science Core Collection database (WoSCC). Trends in publications and citations were analyzed using Excel 2021. VOSviewer and Citespace were used to perform bibliometrics analysis. RESULTS: 36,266 publications on H. pylori were retrieved from the WoSCC database. In general, we observed an increasing trend in the number of publications over the past 20 years. The United States was the most productive and influential country, with the largest proportion of both publications and total citations. Helicobacter, US Department of Veterans Affairs, and Graham, David were the most productive journals, institutions and authors, respectively. Further analysis the co-occurrence and burst detection of keywords revealed that the most common keywords were "Helicobacter pylori," "gastric cancer," and "gastritis," all keywords were divided into eight main clusters, and the most important current research hotspot was the relationship between H. pylori infection and the changes of gut microbiota. CONCLUSIONS: The United States has been the most productive and influential country on H. pylori research, and H. pylori-related research remains an active research field. The relationship between H. pylori infection and the changes of gut microbiota is a research hotspot attracting significant attention.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Helicobacter , Humanos , Bibliometria , Bases de Dados Factuais , Infecções por Helicobacter/epidemiologiaRESUMO
BACKGROUND AND AIM: Acute pancreatitis (AP) is potentially fatal. Therefore, early identification of patients at a high mortality risk and timely intervention are essential. This study aimed to establish an explainable machine-learning model for predicting in-hospital mortality of intensive care unit (ICU) patients with AP. METHODS: Data on patients with AP, including demographics, vital signs, laboratory tests, comorbidities, treatment, complication, and severity scores, were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU collaborative research database (eICU-CRD). Based on the data from MIMIC-IV, we used the least absolute shrinkage and selection operator algorithm to select variables and then established 9 machine-learning models and screened the optimal model. Data from the eICU-CRD were used for external validation. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, decision curve, and calibration plots were used to assess the models' efficacy. Shapley's additive explanation values were used to explain the model. RESULTS: Gaussian naive Bayes (GNB) model had the best performance on the data from MIMIC-IV, with an AUC, accuracy, sensitivity, and specificity of 0.840, 0.787, 0.839, and 0.792, respectively. The GNB model also performed well on the data from the eICU-CRD, with an AUC, accuracy, sensitivity, and specificity of 0.862, 0.833, 0.848, and 0.763, respectively. According to Shapley's additive explanation values, the top 4 predictive factors were maximum red cell distribution width, minimum saturation of blood oxygen, maximum blood urea nitrogen, and the Sequential Organ Failure Assessment score. CONCLUSION: The GNB model demonstrated excellent performance and generalizability in predicting mortality in ICU patients with AP. Therefore, it can identify patients at a high mortality risk.
RESUMO
BACKGROUND AND AIM: Acute pancreatitis is the main cause of hospitalization for pancreatic disease. Some patients tend to have recurrent episodes after experiencing an episode of acute pancreatitis. This study aimed to construct predictive models for recurrent acute pancreatitis (RAP). METHODS: A total of 531 patients who were hospitalized for the first episode of acute pancreatitis at the Affiliated Hospital of Southwest Medical University from January 2018 to December 2019 were enrolled in the study. We confirmed whether the patients had a second episode until December 31, 2021, through an electronic medical record system and telephone or WeChat follow-up. Clinical and follow-up data of patients were collected and randomly allocated to the training and test sets at a ratio of 7:3. The training set was used to select the best model, and the selected model was tested with the test set. The area under the receiver operating characteristic curves, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, decision curve, and calibration plots were used to assess the efficacy of the models. Shapley additive explanation values were used to explain the model. RESULTS: Considering multiple indices, XGBoost was the best model. The area under the receiver operating characteristic curves, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model in the test set were 0.779, 0.763, 0.883, 0.647, 0.341, and 0.922, respectively. According to the Shapley additive explanation values, drinking, smoking, higher levels of triglyceride, and the occurrence of ANC are associated with RAP. CONCLUSION: The XGBoost model shows good performance in predicting RAP, which may help identify high-risk patients.
RESUMO
BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) achieves a satisfactory short-term clinical response in patients with achalasia. However, data on mid- and long-term clinical outcomes are limited. We aimed to assess the mid- and long-term efficacy and safety of POEM in achalasia patients. METHODS: Using the pre-designed search strategy, we identified relevant studies that evaluated the efficacy and safety of POEM with a minimum of 2-year follow-up in the Embase, Cochrane, and PubMed databases from inception to January 2021. Primary outcome was pooled mid- and long-term clinical success rate based on the Eckardt score. Secondary outcome was pooled long-term reflux-related adverse events. RESULTS: A total of 21 studies involving 2,698 patients were included. Overall, the pooled clinical success rates with 2-, 3-, 4-, and 5-year follow-ups were 91.3% (95% confidence interval [CI] 88.4-93.6%), 90.4% (95% CI 88.1-92.2%), 89.8% (95% CI 83.6-93.9%), and 82.2% (95% CI 76.6-86.7%), respectively. Besides, the pooled long-term clinical success rates for type I, II, and III achalasia were 86.1% (95% CI 80.9-90.1%; I2 = 0%), 87.9% (95% CI 84.2-90.8%; I2 = 48.354%), and 83.9% (95% CI 72.5-91.2%; I2 = 0%), respectively. Moreover, the pooled incidence of symptomatic reflux and reflux esophagitis was 23.9% (95% CI 18.7-29.9%) and 16.7% (95% CI 11.9-23.1%), respectively. CONCLUSIONS: POEM is associated with a long-term clinical success of 82.2% after 5 years of follow-up. Randomized control trials comparing POEM with laparoscopic Heller myotomy or pneumatic dilation with longer follow-up periods are needed to further demonstrate the long-term safety and efficacy of POEM.
Assuntos
Acalasia Esofágica , Refluxo Gastroesofágico , Miotomia de Heller , Cirurgia Endoscópica por Orifício Natural , Humanos , Acalasia Esofágica/cirurgia , Acalasia Esofágica/complicações , Resultado do Tratamento , Refluxo Gastroesofágico/etiologia , Miotomia de Heller/efeitos adversos , Dilatação , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Esfíncter Esofágico Inferior/cirurgiaRESUMO
BACKGROUND: To evaluate the methodological and reporting quality of published meta-analyses (MAs) in four major gastrointestinal endoscopic journals, and identify the predicted factors for high quality. METHODS: A systematic search was performed in PubMed to identify MAs from 1, January, 2016 to 31, December, 2020 in four major gastrointestinal endoscopic journals (including Digestive Endoscopy, Gastrointestinal Endoscopy, Surgical Endoscopy, and Endoscopy). We collected the characteristics of MAs after filtering unqualified articles, and assessed methodological and reporting qualities for eligible articles by AMSTAR tool and PRISMA checklist, respectively. Logistic regression was used for identifying predictive factors for high quality. RESULTS: A total of 289 MAs were identified after screening by predefined inclusion and exclusion criteria. The scores (mean ± SD) of AMSTAR and PRISMA were 7.73 ± 1.11 and 22.90 ± 1.85, respectively. In PRISMA checklist, some items had less than 50% complete adherence, including item 2 (structured summary), items 5 (protocol and registration), items 12 and 19 (risk of bias in studies), item 27 (funding support). Item 1 (a priori design), item 4 (gray literature research), item 5 (list of included and excluded) were inferior to 50% adherence in AMSTAR tool. We found the predictive factors for high quality through logistic regression analysis: a priori design and funding support were associated with methodological quality. Protocol and registration influenced the methodological and reporting quality closely. CONCLUSION: In general, qualities on the methodology and the reporting of MAs published in the gastrointestinal endoscopic journals are good, but both of which still potentially need further improvement.
Assuntos
Endoscopia Gastrointestinal , Publicações , Humanos , Lista de Checagem , Metanálise como AssuntoRESUMO
Sepsis is a high-incidence disease and demands intensive care. Finding effective treatment is the key to cure sepsis. Studies have shown a lower level of vitamin C in patients with sepsis. Therefore, vitamin C supplementation has become one of the measures to treat sepsis. However, the clinical studies of vitamin C in the treatment of sepsis have been controversial. We performed a meta-analysis to evaluate vitamin C's efficacy and safety in the treatment of sepsis. We searched four electronic databases: PubMed, Embase, Web of Science, and the Cochrane Library, and two researchers independently screened 24 eligible RCTs published in English. Our review demonstrates that intravenous (IV) vitamin C might improve short-term mortality (RR, 0.82; 95% CI, 0.65-1.02; P=0.07; and I 2 = 45%) and overall mortality (RR, 0.86; 95% CI, 0.74-1.01; P=0.06; and I 2 = 51%) of patients with sepsis. Moreover, the SOFA score of patients with sepsis improved significantly after treatment with vitamin C for over 72 hours (RR, 0.26; 95% CI, 0.09-0.42; P=0.002; and I 2 = 0%). The main results of our study were moderate-quality evidence. More high-quality, multicenter RCTs are needed to provide more substantial evidence on the efficacy and safety of IV vitamin C for sepsis.
Assuntos
Ácido Ascórbico , Sepse , Humanos , Ácido Ascórbico/uso terapêutico , Vitaminas/uso terapêutico , Sepse/tratamento farmacológico , Estudos Multicêntricos como AssuntoRESUMO
Pentagalloyl glucose (PGG) is a natural hydrolyzable gallotannin abundant in various plants and herbs. It has a broad range of biological activities, specifically anticancer activities, and numerous molecular targets. Despite multiple studies available on the pharmacological action of PGG, the molecular mechanisms underlying the anticancer effects of PGG are unclear. Here, we have critically reviewed the natural sources of PGG, its anticancer properties, and underlying mechanisms of action. We found that multiple natural sources of PGG are available, and the existing production technology is sufficient to produce large quantities of the required product. Three plants (or their parts) with maximum PGG content were Rhus chinensis Mill, Bouea macrophylla seed, and Mangifera indica kernel. PGG acts on multiple molecular targets and signaling pathways associated with the hallmarks of cancer to inhibit growth, angiogenesis, and metastasis of several cancers. Moreover, PGG can enhance the efficacy of chemotherapy and radiotherapy by modulating various cancer-associated pathways. Therefore, PGG can be used for treating different human cancers; nevertheless, the data on the pharmacokinetics and safety profile of PGG are limited, and further studies are essential to define the clinical use of PGG in cancer therapies.
Assuntos
Glucose , Taninos Hidrolisáveis , Humanos , Taninos Hidrolisáveis/farmacologia , Taninos Hidrolisáveis/metabolismoRESUMO
BACKGROUND: Gender differences remain a serious issue in the gastroenterology field, which negatively affect the career success and academic advancement of female gastroenterologists. In this study, we aim to identify gender differences in the authors of global major Gastroenterology Society guidelines. METHODS: We included six associations and collected guidelines published between 2003 and 2022. The genders of authors were determined and recorded for each guideline. Linear by linear association test was used to assess trends every 5 years. RESULTS: We included 210 guidelines and 461 authors. The proportion of female first and senior authors was 11.3% and 9.8%, respectively. The number of female first and senior authors in most societies has improved over the past 20 years, with the largest increase in the AGA. CONCLUSIONS: Women are still underrepresented among the authors of guidelines. Although gender differences have gained more attention in recent years, there are many obstacles to achieving gender equality.
RESUMO
CONTEXT: Sanguinarine (SAG) is the most abundant constituent of Macleaya cordata (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice in vivo, suggesting its potential for cancer chemotherapy. OBJECTIVE: To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma. MATERIALS AND METHODS: CCK8 assay was used to determine the inhibition of SAG on the proliferation of A375 and A2058 cells. Network pharmacology analysis was applied to construct a compound-target network and select potential therapeutic targets of SAG against melanoma. Molecular docking simulation was conducted for further analysis of the selected targets. In vitro migration/invasion/western blot assay with 1, 1.5, 2 µM SAG and in vivo effect of 2, 4, 8 mg/kg SAG in xenotransplantation model in nude mice. RESULTS: The key targets of SAG treatment for melanoma were mainly enriched in PI3K-AKT pathway, and the binding energy of SAG to PI3K, AKT, and mTOR were -6.33, -6.31, and -6.07 kcal/mol, respectively. SAG treatment inhibited the proliferation, migration, and invasion ability of A375 and A2058 cells (p < 0.05) with IC50 values of 2.378 µM and 2.719 µM, respectively. It also decreased the phosphorylation levels of FAK, PI3K, AKT, mTOR and protein expression levels of MMP2 and ICAM-2. In the nude mouse xenograft model, 2, 4, 8 mg/kg SAG was shown to be effective in inhibiting tumour growth. CONCLUSIONS: Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic.
Assuntos
Melanoma , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Antígenos CD/metabolismo , Moléculas de Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos Nus , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Peroral endoscopic myotomy (POEM) is a particularly attractive intervention for achalasia. Presently, POEM has been reported to be effective and safe for achalasia in geriatric patients. Herein, this systematic review was conducted to explore the role of POEM in geriatric patients with achalasia. METHOD: PubMed, Embase, and Cochrane Library were searched to identify studies evaluating the clinical outcome of POEM in geriatric patients with achalasia during January 2009 to October 2020. The primary outcomes were technical and clinical success. Secondary outcomes included postoperative Eckardt score, lower esophageal sphincter (LES) pressure, adverse events, and clinical reflux. RESULTS: There were 7 studies with a total of 469 geriatric patients, and the pooled technical success of POEM treatment was 98.1% (95% confidence interval [CI], 95.1-99.3%), and the pooled clinical success was 92.5% (95% CI, 89.3-94.8%). After POEM, the Eckardt score significantly decreased by 6.09 points (95% CI, 5.44-6.74, p < 0.00001), and the LES pressure significantly reduced by 13.53 mm Hg (95% CI, 5.14-21.91, p = 0.002). The pooled adverse events rate was 9.0% (95% CI, 4.3-17.9%), and the post-POEM clinical reflux rate was 17.4% (95% CI, 12.9-23.2%). CONCLUSION: Our current study demonstrated that POEM was an effective and safe technique for achalasia in geriatric patients.
Assuntos
Acalasia Esofágica , Miotomia , Cirurgia Endoscópica por Orifício Natural , Idoso , Acalasia Esofágica/cirurgia , Esfíncter Esofágico Inferior , Esofagoscopia , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Zenker's peroral endoscopic myotomy (Z-POEM) has revolutionized the therapeutic strategy for Zenker's diverticulum (ZD) with promising results. We conducted this meta-analysis to estimate the safety and efficacy of Z-POEM for ZD and compare the feasibility and effectiveness of Z-POEM with that of flexible endoscopic septotomy (FES). METHODS: A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, and Cochrane Library databases to query for studies that assessed the safety and efficacy of Z-POEM for ZD. All articles published from inception to July 31, 2021 were included. The primary outcomes were the overall technical success rate, clinical success rate, incidence of adverse events, and clinical recurrence rate. RESULTS: Eleven studies involving 357 patients undergone Z-POEM were included. Overall, the quality of included studies was above average, with five studies rated as high quality and six ranked as moderate quality. The overall pooled technical success rate for Z-POEM was 96.3% (95% confidence interval [CI] 93.6-97.9%; I2 = 0%). The total pooled clinical success rate for Z-POEM was 93.0% (95% CI 89.4-95.4%; I2 = 0%). The pooled incidence of adverse events for Z-POEM was 12.4% (95% CI 9.1-16.7%; I2 = 0%). The pooled clinical recurrence rate for Z-POEM was 11.2% (95% CI 7.6-16.2%; I2 = 0%). The clinical success for Z-POEM was significantly better than that of FES (relative risk [RR]: 1.11; CI 95% 1.03-1.18; p = 0.004, I2 = 0%), while there were no significant differences in technical success, adverse events, and clinical recurrence between Z-POEM and FES. CONCLUSION: Z-POEM could be an effective and safe therapeutic modality for ZD, and even has a slightly higher clinical success rate than FES. However, comparative studies with long-term follow-up will be needed to further confirm our finding.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Miotomia , Divertículo de Zenker , Esofagoscopia/efeitos adversos , Humanos , Miotomia/métodos , Resultado do Tratamento , Divertículo de Zenker/cirurgiaRESUMO
INTRODUCTION: Retrospection of retracted articles has important implications for research into the ethics of academic publishing. METHODS: A search was performed of the Retraction Watch database for retracted articles in the field of gastroenterology. RESULTS: A total of 583 retractions were included and around 76 percent were retracted since 2015. Over half of the retractions focused on digestive system neoplasms. Issues of reliability of the contents, duplication and plagiarism were common reasons for retraction. DISCUSSION: Only a few retractions were due to honest errors, while many articles were retracted by authors due to committing some kind of misconduct.
Assuntos
Pesquisa Biomédica , Gastroenterologia , Má Conduta Científica , Humanos , Plágio , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Review of retracted articles has a positive impact on scientific research. The aim of our study was to examine the characteristics of retracted articles in the field of pancreatic diseases. METHODS: The Retraction Watch database was queried for retractions in pancreatic diseases on 7 March 2021, and the filters set were as follows: (1) the Title typed in was "pancreatitis", "pancreas", or "pancreatic"; (2) the Nature of notice selected was "retraction". RESULTS: A total of 116 retracted articles were identified as pancreatic disease-related, with over two-thirds of them pertaining to pancreatic cancer. Research article was the most common article type among these retractions. Common reasons given for retraction included scientific fraud (37.1%), duplication (26.7%), and reliability (25%). China had the largest number of retractions (n=51), followed by the United States (n=47). Most articles were retracted in recent years, particularly after 2015. CONCLUSIONS: A large proportion of retracted articles pertaining to pancreatic diseases have been retracted in recent years. The majority of publications-over three quarters-were retracted for authors who committed some type of misconduct. Differences between countries in the manner of misconduct were stark.