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Background: We conducted an assessment of 2'-O-methylated (2'OMe) microRNAs (miRNAs) present in the circulation of individuals suffering from pancreatic ductal adenocarcinoma (PDAC). Subsequently, we devised a set of circulating 2'OMe miRNAs that can be utilized for the screening of PDAC patients within a group at increased risk. Methods: A four-step, multicenter research was carried out. The initial screening phase involved analyzing 10 samples from patients with pancreatic ductal adenocarcinoma (PDAC) and 10 specimens from donors who were in good health. RNA sequencing was performed on these specimens after pre-treatment via NaIO4. The instruction and confirmation phases involved the use of 2'OMe miRNA profiling and multivariate analysis to examine applicant 2'OMe miRNAs in a sample of 248 individuals. In a prospective registration population of 135 individuals, a clinical screening panel was created and confirmed. The performance of individual 2'OMe miRNAs or the biomarker panel was evaluated using the receiver operating characteristic curve. Results: Abnormal circulating 2'OMe miRNAs were detected in individuals suspected of pancreatic ductal adenocarcinoma (PDAC). A circulating panel of 3-2'OMe miRNAs, namely miR-28-3p, miR-143-3p, and miR-151a-3p, was subsequently identified. These miRNAs continually exhibited up-regulation in plasma samples of patients with pancreatic ductal adenocarcinoma (PDAC). The panel's area under the curve (AUC) was 1.0 in the experimental group and 0.928 in the verification cohort when comparing PDAC patients in all clinical stages to normal controls. During the application study, both the specificity and sensitivity were found to be 75.00% and 89.72% respectively, with an AUC value of 0.868. In the comparison between early-stage (I-II) PDAC patients and control subjects, the panel demonstrated an AUC of 1.0 in the training cohort and 0.924 in the validation population. In the application group the AUC was 0.810 (95% CI 0.729-0.876) in comparison to the high-risk symptomatic group. Conclusion: Abnormal circulating 2'OMe miRNAs were detected in individuals with pancreatic ductal adenocarcinoma (PDAC). Consequently, we devised a 2'OMe miRNA biological marker panel that holds promise as an initial detection tool for PDAC.
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OBJECTIVES: The objective of this study was to develop clinical scores to predict the risk of intensive care unit (ICU) admission in patients with COVID-19 and end stage kidney disease (ESKD). METHODS: This was a prospective study in which 100 patients with ESKD were enrolled and divided into two groups: the ICU group and the non-ICU group. We utilized univariate logistic regression and nonparametric statistics to analyze the clinical characteristics and liver function changes of both groups. By plotting receiver operating characteristic curves, we identified clinical scores that could predict the risk of ICU admission. RESULTS: Out of the 100 patients with Omicron infection, 12 patients were transferred to the ICU due to disease aggravation, with an average of 9.08 days from hospitalization to ICU transfer. Patients transferred to the ICU more commonly experienced shortness of breath, orthopnea, and gastrointestinal bleeding. The peak liver function and changes from baseline in the ICU group were significantly higher, with p values <.05. We found that the baseline platelet-albumin-bilirubin score (PALBI) and neutrophil-to-lymphocyte ratio (NLR) were good predictors of ICU admission risk, with area under curve values of 0.713 and 0.770, respectively. These scores were comparable to the classic Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (p > .05). CONCLUSION: Patients with ESKD and Omicron infection who are transferred to the ICU are more likely to have abnormal liver function. The baseline PALBI and NLR scores can better predict the risk of clinical deterioration and early transfer to the ICU for treatment.
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COVID-19 , Fallo Renal Crónico , Humanos , Estudios Prospectivos , Neutrófilos , COVID-19/complicaciones , SARS-CoV-2 , Hospitalización , Linfocitos , Unidades de Cuidados Intensivos , Fallo Renal Crónico/terapia , Albúminas , Curva ROC , Pronóstico , Estudios RetrospectivosRESUMEN
Colonoscopy is effective in the prevention and screening of colorectal cancer. Whether terminal ileal (TI) intubation is required during conventional colonoscopy and whether it offers clinical benefits with respect to polyp detection rate (PDR) remain unclear. This retrospective study included patients who underwent colonoscopy at our hospital between July 1, 2018 and April 20, 2019. The positive findings and time for TI intubation were recorded. Univariate and multivariate analyses were performed to identify factors associated with PDR. There were 1675 patients with cecal intubation colonoscopy, including 994 (59â%) with TI intubation and 8 (1â%) with intestinal disease. The mean time for TI intubation was 40 seconds (3-338), and the mean time from cecal intubation to arrival at the deep part of TI mucosa was 24 seconds (2-118). The overall PDR was 27â%. On multivariable analysis, age >â50 years [95â% confidence interval (CI) 2.837-4.590], male sex (95â%CI, 0.406-0.649), presence of symptoms (abdominal symptoms vs. asymptomatic, 95â% CI, 1.146-2.468; stool changes vs. asymptomatic, 95â% CI, 1.070-1.834), and non-TI intubation (95â% CI, 1.040-1.648) were independent predictors of higher PDR. Trend analysis indicated decreasing trend of PDR among non-TI intubation group, 0-5âcm TI intubation group, and >â5âcm TI intubation group (30â% vs. 27â% vs. 24â%, respectively; pâ<â0.05). TI intubation is necessary to identify small bowel disease among a designated population, but it was not suggested to be routinely performed as part of colonoscopy, owing to limited positive intestinal findings, extra time requirement, and possible PDR worsening.
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Pólipos del Colon/patología , Colonoscopía/métodos , Intubación Intratraqueal , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Íleon , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Patient screening is important for early diagnosis of colorectal cancer (CRC). The present study aimed to compare the multitarget stool DNA (mt-sDNA) test with the fecal occult blood test (FOBT) for CRC screening. A total of 151 individuals were screened using colonoscopy, mt-sDNA and FOBT for the detection of CRC and adenoma. The results of the mt-sDNA test and FOBT were compared with colonoscopy to examine their sensitivity and specificity. Subsequently, the sensitivity and specificity of the mt-sDNA test were compared with those of FOBT in CRC and large adenoma. Stool samples were collected from patients with CRC (n=50) or large adenoma (n=51), as well as from normal controls (n=50). The mt-sDNA test outperformed FOBT in detecting CRC with a sensitivity of 90.0% (45/50) vs. 42.0% (21/50), advanced adenoma with a sensitivity of 70.6% (36/51) vs. 19.6% (10/51), stage I-III CRC with a sensitivity of 91.9% (34/37) vs. 29.7% (11/37), and stage IV CRC with a sensitivity of 84.6% (11/13) vs. 76.9% (10/13). In addition, the mt-sDNA test exhibited a specificity of 94.0% (47/50) in detecting CRC, which was superior to FOBT with a specificity of 90.0% (45/50). Therefore, the mt-sDNA test may have higher sensitivity and specificity compared with FOBT in diagnosing both CRC and advanced adenoma.
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To establish a screening strategy for pancreatic cancer (PC) based on new-onset diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the metabolic pathways associated with PC related DM were performed. Serum samples from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM were examined by liquid chromatography-mass spectrometry. Data were analyzed using principal components analysis (PCA) and orthogonal projection to latent structures (OPLS) of the most significant metabolites. The diagnostic model was constructed using logistic regression analysis. Metabolic pathways were analyzed using the web-based tool MetPA. PC patients with NO-DM were older and had a lower BMI and shorter duration of DM than those with NO-DM. The metabolomic profiles of patients with PC and NO-DM were significantly different from those of patients with NO-DM in the PCA and OPLS models. Sixty two differential metabolites were identified by the OPLS model. The logistic regression model using a panel of two metabolites including N_Succinyl_L_diaminopimelic_acid and PE (18:2) had high sensitivity (93.3%) and specificity (93.1%) for PC. The top three metabolic pathways associated with PC related DM were valine, leucine and isoleucine biosynthesis and degradation, primary bile acid biosynthesis, and sphingolipid metabolism. In conclusion, screening for PC based on NO-DM using serum metabolomics in combination with clinic characteristics and CA19-9 is a potential useful strategy. Several metabolic pathways differed between PC related DM and type 2 DM.
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Adenocarcinoma/sangre , Carcinoma Ductal Pancreático/sangre , Diabetes Mellitus Tipo 2/sangre , Redes y Vías Metabólicas , Metabolómica/métodos , Neoplasias Pancreáticas/sangre , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adulto , Factores de Edad , Anciano , Biomarcadores de Tumor/sangre , Índice de Masa Corporal , Antígeno CA-19-9/sangre , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Cromatografía Liquida , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico Diferencial , Detección Precoz del Cáncer/métodos , Estudios de Factibilidad , Femenino , Humanos , Isoleucina/metabolismo , Leucina/metabolismo , Metabolismo de los Lípidos , Masculino , Espectrometría de Masas , Metaboloma , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Análisis de Componente Principal , Sensibilidad y Especificidad , Pruebas Serológicas/métodos , Valina/metabolismoRESUMEN
Severe acute pancreatitis (SAP) accounts for up to 20% of acute pancreatitis (AP) cases. The absence of effective treatment options has resulted in a high rate of morbidity and mortality. Emodin is a major component of the Chinese herb rhubarb, which has been widely used in the treatment of numerous diseases, including inflammation and cancer. There are a limited number of studies however, that have investigated the effectiveness of emodin in the treatment of SAP. The present study used a rat model of SAP, to investigate the effect and molecular mechanisms of emodin treatment. Administration of emodin was identified to significantly attenuate SAP, as determined by serum amylase analysis and histological assessment of edema, vacuolization, inflammation and necrosis (P<0.01). Furthermore, treatment with emodin markedly inhibited nuclear factor (NF)κB DNAbinding activity (P<0.01) and the serum expression levels of tumor necrosis factorα, interleukin (IL)6 and IL1ß (P<0.05). This attenuation was associated with decreased malondialdehyde and increased superoxide dismutase levels in the pancreatic tissues and serum (P<0.05). This study indicated that administration of exogenous emodin had therapeutic effects on the severity of SAP. The mechanism may be due to inhibition of NFκB activation resulting in an antioxidation response, which can subsequently suppress the expression of cytokines.
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Antioxidantes/farmacología , Emodina/farmacología , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Pancreatitis/patología , Enfermedad Aguda , Amilasas/sangre , Animales , Antioxidantes/uso terapéutico , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Emodina/uso terapéutico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Estimación de Kaplan-Meier , Masculino , Malondialdehído/análisis , Malondialdehído/sangre , FN-kappa B/antagonistas & inhibidores , Pancreatitis/tratamiento farmacológico , Pancreatitis/mortalidad , Ratas , Ratas Sprague-Dawley , Rheum/química , Rheum/metabolismo , Índice de Severidad de la Enfermedad , Superóxido Dismutasa/análisis , Superóxido Dismutasa/sangre , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality in the United States. There is no effective serum biomarker for the early diagnosis of PC at present. Although serum UL16-binding protein 2 (ULBP2) and macrophage inhibitory cytokine-1 (MIC-1) levels are reported to be elevated in PC patients, the diagnostic and prognostic value of ULBP2 and MIC-1 alone or in combination remains unknown. The aim of the present case-control study was to compare the diagnostic value of ULBP2, MIC-1 and carbohydrate antigen 19-9 (CA19-9) in 359 serum samples, consisting of 152 cases of PC, 20 cases of pre-pancreatic cancer, 91 cases of chronic pancreatitis (CP) and 96 normal controls (NC). All patients were followed up for a median of 2 years. It was found that the serum levels of ULBP2, MIC-1 and CA19-9 were significantly higher in the PC patients compared with those in the NC group. In distinguishing PC from the CP, the highest sensitivity and specificity were ULBP2 (0.878) and CA19-9 (0.816), respectively. The area under the receiver operating characteristic curve of ULBP2 was 0.923, which was the highest of the three biomarkers. MIC-1 was the optimal choice for the diagnosis of early-stage PC (area under the curve, 0.831). Overall, MIC-1 in combination with ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC. In addition, a higher level of MIC-1 was correlated with a poorer prognosis, as calculated by the Kaplan-Meier test (P=0.039). Patients with serum MIC-1 levels of ≥1,932 ng/ml had a median survival time of 15.62±2.44 months (mean ± standard deviation) vs. 18.66±2.43 months in patients with a lower level of MIC-1. Overall, combined detection of serum MIC-1 and ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC, and serum MIC-1 level alone was a predictor of survival in the patients with PC.
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A 62-year-old woman was admitted to our hospital in 2011 because of recurrent abdominal pain, nausea and constipation for six months. Computed tomography enterography (CTE) showed tortuous thread-like calcifications in the ileocolic vein and right colic vein, while colonoscopy revealed purple-blue mucosa extending from the cecum to the splenic flexure. Based on the results of these tests, the patient was diagnosed with idiopathic mesenteric phlebosclerosis (IMP). She had a history of Chinese medical liquor intake for one and a half years and her symptoms subsided after conservative treatment. In 2013, a 63-year-old male patient who presented with recurrent lower right abdominal pain, bloating, melena and diarrhea for fifteen months was admitted to our institution. Colonoscopy and CTE led to the diagnosis of IMP. He also used Chinese medical liquor for approximately 12 years. The patient underwent total colectomy and the postoperative course was uneventful. We searched for previously published reports on similar cases and analyzed the clinical data of 50 cases identified in PubMed. As some of these patients admitted use of Chinese medicines, we hypothesize that Chinese medicines may play a role in the pathogenesis of IMP.
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Medicamentos Herbarios Chinos/efectos adversos , Mesenterio/irrigación sanguínea , Calcificación Vascular/inducido químicamente , Colonoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Flebografía/métodos , Valor Predictivo de las Pruebas , Factores de Riesgo , Esclerosis , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Calcificación Vascular/diagnóstico , Calcificación Vascular/terapia , Venas/efectos de los fármacos , Venas/patologíaRESUMEN
Based on the function of chemokine fractalkine (FKN), acting as both adhesion and chemoattractant, FKN plays a role in acute inflammatory response. In this study, we investigated the mechanism of FKN mediated upregulation inflammation in severe acute pancreatitis (SAP) rat models. Western blot, reverse transcriptase-polymerase chain reaction, and immunofluorescence demonstrated that FKN and its receptor CX3CR1 were overexpressed in cerulein-stimulated AR42J cells. AG490 and FKN-siRNA inhibited activation of Janus kinase/signal transducers and activators of transcription (Jak/Stat) in cerulein-stimulated AR42J cells. Following exposure AG490 and FKN-siRNA inhibited tumor necrosis factor-alpha expression by enzyme-linked immunosorbent assay and immunohistochemistry in vivo the SAP rat models. These results showed FKN and CX3CR1 were involved inflammatory response in cerulein-stimulated AR42J cells. FKN upregulates inflammation through CX3CR1 and the Jak/Stat pathway in SAP rat models.
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Quimiocina CX3CL1/metabolismo , Quinasas Janus/metabolismo , Pancreatitis/metabolismo , Receptores de Quimiocina/metabolismo , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Receptor 1 de Quimiocinas CX3C , Línea Celular , Ceruletida/farmacología , Inflamación/inducido químicamente , Inflamación/metabolismo , Mediadores de Inflamación , Quinasas Janus/antagonistas & inhibidores , Pancreatitis/inducido químicamente , Interferencia de ARN , ARN Interferente Pequeño , Ratas , Ratas Sprague-Dawley , Receptores de Quimiocina/genética , Factor de Transcripción STAT1/antagonistas & inhibidores , Factor de Transcripción STAT3/antagonistas & inhibidores , Transducción de Señal , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia ArribaRESUMEN
In China, the number of hospitals has increased to 19,712 in 2008, with the production of hospital wastewater reaching 1.29 × 106 m3/d. Membrane bioreactor (MBR) technology presents a more efficient system at removing pathological microorganism compared with existing wastewater treatment systems. In the past 8 yr, over 50 MBR plants have been successfully built for hospital wastewater treatments, with the capacity ranging from 20 to 2000 m3/d. MBR can effectively save disinfectant consumption (chlorine addition can decrease to 1.0 mg/L), shorten the reaction time (approximately 1.5 min, 2.5-5% of conventional wastewater treatment process), and attain a good effect of inactivation of microorganism. Higher disinfection efficacy is achieved in MBR effluents at lower dose of disinfectant with less disinfection by-products (DBPs). Moreover, when capacity of MBR plants increases from 20 to 1000 m3/d, their operating cost decreases sharply.
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The effect of derivatives of sulfur dioxide (SO(2)), a common air pollutant, which exists in vivo at equilibrium between bisulfate and sulfite, was studied on hyperpolarization-activated cation current (I(h)) in cultured post-natal dorsal root ganglion (DRG) neurons using the whole cell configuration of patch-clamp technique. SO(2) derivatives increased I(h) current in a dose and voltage-dependent manner. The EC(50) value was 25 microM and the Hill coefficient was 1.44. 50 microM SO(2) derivatives significantly shifted the activation curve of I(h) in the hyperpolarizing direction by 5.5 mV. The reversal potential of I(h) was shifted to 5.2 mV in positive direction by 10 microM SO(2) derivatives. According to the functional role of I(h), the increase of I(h) should result in an enhanced neuronal excitability, which was possibly the basis for neuropathic pain.