RESUMEN
BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels. METHODS: AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide (LPS). Additionally, using Ptf1α to drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J- hM3/Ptf1α(cre) mice were administered Clozapine N-oxide to induce AP. Subsequently, we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus (GEO) database. RESULTS: Caerulein-induced AP showed severe inflammation and edema, which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis. Compared with the control group, RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway, TLR signaling pathway, and NF-κB signaling pathway, alongside elevated levels of apoptosis-related pathways, such as apoptosis, P53 pathway, and phagosome pathway. The significantly elevated genes in the TLR and NOD-like receptor signaling pathways, as well as in the apoptosis pathway, were validated through quantitative real-time PCR experiments in animal models. Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood, while TLR1, TLR7, RIPK3, and OAS2 genes exhibited marked elevation in human AP. The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP. The transgenic mouse model hM3/Ptf1α(cre) successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway, indicating that these pathways represent shared pathological processes in AP across different models. CONCLUSION: The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP, notably the MYD88 gene. Apoptosis holds a central position in the necrotic processes of AP, with TUBA1A and GADD45A genes exhibiting prominence in human AP.
Asunto(s)
Ceruletida , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Lipopolisacáridos , Ratones Endogámicos C57BL , Ratones Transgénicos , Páncreas , Pancreatitis , Factores de Transcripción , Animales , Ceruletida/toxicidad , Ratones , Pancreatitis/genética , Pancreatitis/inducido químicamente , Pancreatitis/patología , Pancreatitis/metabolismo , Perfilación de la Expresión Génica/métodos , Páncreas/patología , Páncreas/metabolismo , Humanos , Transcriptoma , Masculino , Transducción de Señal , Células Acinares/metabolismo , Células Acinares/patologíaRESUMEN
BACKGROUND & AIMS: The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aimed to evaluate the role of PTEN in the pathogenesis of eCCA and identify novel therapeutic targets for this disease. METHODS: The Pten gene was genetically deleted using the Cre-loxp system in biliary epithelial cells. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry, reverse-transcription PCR, cell culture, and RNA sequencing. Some features were compared to those in human eCCA samples. Further mechanistic studies utilized the conditional knockout of Trp53 and Aurora kinase A (Aurka) genes. We also tested the effectiveness of an Aurka inhibitor. RESULTS: We observed that genetic deletion of the Pten gene in the extrahepatic biliary epithelium and peri-ductal glands initiated sclerosing cholangitis-like lesions in mice, resulting in enlarged and distorted extrahepatic bile ducts in mice as early as 1 month after birth. Histologically, these lesions exhibited increased epithelial proliferation, inflammatory cell infiltration, and fibrosis. With aging, the lesions progressed from low-grade dysplasia to invasive carcinoma. Trp53 inactivation further accelerated disease progression, potentially by downregulating senescence. Further mechanistic studies showed that both human and mouse eCCA showed high expression of AURKA. Notably, the genetic deletion of Aurka completely eliminated Pten deficiency-induced extrahepatic bile duct lesions. Furthermore, pharmacological inhibition of Aurka alleviated disease progression. CONCLUSIONS: Pten deficiency in extrahepatic cholangiocytes and peribiliary glands led to a cholangitis-to-cholangiocarcinoma continuum that was dependent on Aurka. These findings offer new insights into preventive and therapeutic interventions for extrahepatic CCA. IMPACT AND IMPLICATIONS: The aberrant PTEN-PI3K-AKT signaling pathway is commonly observed in human extrahepatic cholangiocarcinoma (eCCA), a disease with a poor prognosis. In our study, we developed a mouse model mimicking cholangitis to eCCA progression by conditionally deleting the Pten gene via Pdx1-Cre in epithelial cells and peribiliary glands of the extrahepatic biliary duct. The conditional Pten deletion in these cells led to cholangitis, which gradually advanced to dysplasia, ultimately resulting in eCCA. The loss of Pten heightened Akt signaling, cell proliferation, inflammation, fibrosis, DNA damage, epigenetic signaling, epithelial-mesenchymal transition, cell dysplasia, and cellular senescence. Genetic deletion or pharmacological inhibition of Aurka successfully halted disease progression. This model will be valuable for testing novel therapies and unraveling the mechanisms of eCCA tumorigenesis.
Asunto(s)
Aurora Quinasa A , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Fosfohidrolasa PTEN , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Animales , Aurora Quinasa A/genética , Aurora Quinasa A/metabolismo , Colangiocarcinoma/etiología , Colangiocarcinoma/patología , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Ratones , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/etiología , Neoplasias de los Conductos Biliares/metabolismo , Humanos , Ratones Noqueados , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Conductos Biliares Extrahepáticos/patología , Modelos Animales de Enfermedad , Colangitis/patología , Colangitis/etiología , Colangitis/metabolismo , Colangitis/genética , Transducción de SeñalRESUMEN
BACKGROUND: The aim of this current study was to identify the prevalence and risk factors of H. pylori infection in the low-risk area of gastric cancer in China, and evaluate the value of different gastric cancer screening methods. METHODS: An epidemiological study was conducted in Yudu County, Jiangxi, China, and participants were followed up for 6 years. All participants completed a questionnaire, laboratory tests and endoscopy. Patients were divided into H. pylori positive and negative groups, and risk factors for H. pylori infection were identified using multivariate logistic regression analysis. RESULTS: A total of 1962 residents were included, the prevalence of H. pylori infection was 33.8%. Multivariate analysis showed that annual income ≤20,000 yuan (OR: 1.44, 95% CI: 1.18-1.77, p < 0.001), loss of appetite (OR: 1.71, 95% CI: 1.29-2.26, p < 0.001), PG II >37.23 ng/mL (OR: 2.11, 95% CI: 1.50-2.97, p < 0.001), G-17 > 1.5 and ≤5.7 pmol/L (OR: 2.52, 95% CI: 1.93-3.30, p < 0.001), and G-17 > 5.7 pmol/L (OR: 1.96, 95% CI: 1.48-2.60, p < 0.001) were risk factors of H. pylori infection, while alcohol consumption (OR: 0.70, 95% CI: 0.54-0.91, p = 0.006) was a protective factor. According to the new gastric cancer screening method, the prevalence of low-grade intraepithelial neoplasia in the low-risk group, medium-risk group and high-risk group was 4.4%, 7.7% and 12.5% respectively (p < 0.001). CONCLUSIONS: In a low-risk area of gastric cancer in China, the infection rate of H. pylori is relatively low. Low income, loss of appetite, high PG II, and high G-17 were risk factors for H. pylori infection, while alcohol consumption was a protective factor. Moreover, the new gastric cancer screening method better predicted low-grade intraepithelial neoplasia than the ABC method and the new ABC method.
Asunto(s)
Infecciones por Helicobacter , Neoplasias Gástricas , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/microbiología , China/epidemiología , Prevalencia , Factores de Riesgo , Helicobacter pylori , Infecciones por Helicobacter/complicaciones , Detección Precoz del Cáncer , Humanos , Adulto , Persona de Mediana Edad , Anciano , Masculino , FemeninoRESUMEN
BACKGROUND: At present, the relationship between severe acute pancreatitis (SAP) and albumin infusion is not clear. We aimed to identify the impact of serum albumin on the prognosis of SAP and the association between albumin infusions and mortality for hypoalbuminemia patients. METHODS: This was a retrospective cohort study that analyzed 1000 patients with SAP who were admitted to the First Affiliated Hospital of Nanchang University between January 2010 and December 2021 using data from a prospectively maintained database. Multivariate logistic regression analysis was conducted to reveal the relationship between serum albumin within 1 week after admission and poor prognosis of SAP. Propensity score matching (PSM) analysis was adopted to evaluate the effect of albumin infusion for hypoalbuminemia patients with SAP. RESULTS: The prevalence of hypoalbuminemia (≤ 30 g/L) was 56.9% within 1 week after admission. Multivariate logistic regression identified that age (OR: 1.02; 95% CI: 1.00-1.04; P = 0.012), serum urea (OR: 1.08; 95% CI: 1.04-1.12; P < 0.001), serum calcium (OR: 0.27; 95% CI: 0.14-0.50; P < 0.001), lowest albumin level within 1 week after admission (OR: 0.93; 95% CI: 0.89-0.97; P = 0.002), and APACHE II score ≥ 15 (OR: 1.73; 95% CI: 1.19-2.51; P = 0.004) were independently associated with mortality. The PSM analysis demonstrated that mortality (OR: 0.52, 95% CI: 0.29-0.92, P = 0.023) was less common in albumin-infused than non-albumin-infused hypoalbuminemia patients. In subgroup analyses, doses > 100 g within 1 week after admission for hypoalbuminemia patients with albumin infusions was associated with lower mortality than doses ≤ 100 g (OR: 0.51, 95% CI: 0.28-0.90, P = 0.020). CONCLUSIONS: Hypoalbuminemia in early-stage SAP is significantly related to poor prognosis. However, albumin infusions could significantly decrease mortality in hypoalbuminemia patients with SAP. Additionally, infusing sufficient albumin within a week after admission may decrease mortality in hypoalbuminemia patients.
Asunto(s)
Hipoalbuminemia , Pancreatitis , Humanos , Pancreatitis/complicaciones , Pancreatitis/tratamiento farmacológico , Estudios Retrospectivos , Enfermedad Aguda , Albúmina Sérica , Pronóstico , Factores de RiesgoRESUMEN
In the oil industry, oil spills occur due to offshore rig explosions, ship collisions, and other reasons. It is crucial to accurately and rapidly identify oil spills to protect marine ecosystems. Synthetic aperture radar (SAR) can all-weather and all-time work and provide a wealth of polarization information for identification of oil spills based on semantic segmentation model. However, the performance of classifiers in the semantic segmentation model has become a significant challenge to improving recognition ability. To solve this problem, an improved semantic segmentation model named DRSNet was proposed, which uses ResNet-50 as the backbone in DeepLabv3+ and support vector machines (SVM) as the classifier. The experiment was conducted using ten polarimetric features from SAR images and results demonstrate that the DRSNet performs best compared to other semantic segmentation models. Current work provides a valuable tool to enhance maritime emergency management capabilities.
Asunto(s)
Contaminación por Petróleo , Contaminantes Químicos del Agua , Máquina de Vectores de Soporte , Contaminantes Químicos del Agua/análisis , Radar , Ecosistema , Semántica , Monitoreo del Ambiente/métodosRESUMEN
Aim: To analyze the clinical profile of patients with acute hypertriglyceridemic pancreatitis (HTGP) and explore risk factors for recurrence. Methods: A retrospective observational study was conducted in patients who experienced an attack of HTGP for the first time. Patients were followed until the recurrence of acute pancreatitis (AP) or 1 year. The detailed clinical profile was compared between patients with or without recurrence. Multivariate logistic regression analysis was conducted to explore independent risk factors for recurrence. Results: A total of 108 HTGP patients were included in this study with 73.1% being male, and the median age being 37 (interquartile range, IQR, 30.3-44.8) years. Recurrence occurred in 70 patients (64.8%). Compared with the nonrecurrent group, serum triglyceride (TG) levels before discharge [4.1 (2.8,6.3) mmol/L vs. 2.9 (2.2,4.2) mmol/L; p = 0.002], at 1 month [3.7 (2.3,9.7) mmol/L vs. 2.0 (1.4,2.7) mmol/L; p = 0.001], at 6 months [6.1 (3.1,13.1) mmol/L vs. 2.5 (1.1,3.5) mmol/L; p = 0.003] and 12 months [9.6 (3.5,20.0) mmol/L vs. 2.7 (1.6,5.5) mmol/L; p = 0.001] after discharge were higher in the recurrent group. Poor control of TG levels (TG > 3.1 mmol/l) at the 1-month follow-up after discharge and a high Charlson's Comorbidity Index score (≥ 2 points) increased the risk of recurrence of HTGP. Conclusion: High TG levels during follow-up and Charlson's Comorbidity Index score were independently associated with recurrence in patients with HTGP.
RESUMEN
BACKGROUND: Data on recurrent hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are scarce. OBJECTIVE: To investigate the incidence and risk factors for recurrence of HTG-AP, and the effect of triglyceride (TG) lowering drugs post index attack on recurrence. METHODS: This study was a prospective cohort study of adult patients with first episode of HTG-AP from December 2019 to February 2021 who were followed until recurrence or death, or February 2022. The cumulative incidence function and Fine and Gray's competing-risk model were applied to the analyses. RESULTS: A total of 317 patients were enrolled, and the 12-month and 18-month cumulative recurrence incidences were 8% and 22%, respectively. The cumulative recurrence incidence was 2 times higher in patients whose serum TG levels post index attack were ≥5.65 mmol/L (subdistribution hazard ratio [SHR], 2.00; 95% confidence interval [CI], 1.05-3.80; P = 0.034) compared to patients with TG <5.65 mmol/L. The recurrence rate was 3.3 times higher in patients whose glucose levels post index attack were ≥7.0 mmol/L (SHR, 3.31; 95% CI, 1.56-7.03; P = 0.002) than in patients with glucose <7.0 mmol/L). Compared to TG lowering drugs for less than 1 month post index attack, treatment for longer than 12 months decreased the incidence of recurrence by 75% (SHR, 0.25; 95% CI, 0.08-0.80; P = 0.019). CONCLUSIONS: The HTG-AP recurrence incidence is high and closely associated with high levels of TGs and glucose post index attack. Long-term TG lowering drugs treatment significantly decreases this recurrence.
Asunto(s)
Hiperlipidemias , Hipertrigliceridemia , Pancreatitis , Adulto , Humanos , Pancreatitis/etiología , Estudios Prospectivos , Enfermedad Aguda , Estudios Retrospectivos , Hiperlipidemias/complicaciones , TriglicéridosRESUMEN
Purpose: High lactate levels at hospital admission are significantly associated with poor prognosis in acute pancreatitis patients. Early high lactate clearance is a vital marker for predicting persistent organ failure and mortality in critical illness; however, its value in acute pancreatitis remains unclear. Method: Data were collected from patients who were diagnosed with moderately severe acute pancreatitis and severe acute pancreatitis from January 2017 to December 2020. Initial lactate (within 2 hours after admission) and repeat lactate at 24 hours after admission were measured to determine lactate clearance. Low clearance was defined as a reduction in repeat lactate of less than 30% compared to the first measurement. High clearance was defined as a repeat lactate decrease ≥30% of the first measurement or both first and second lactate levels <2 mmol/L. Baseline data, laboratory data, mortality rate, persistent organ failure rate, and other outcomes such as the incidence of septic pancreatic necrosis and sepsis and the length of hospital stay and intensive care unit (ICU) stay were compared in the low and high lactate clearance groups. Multivariate logistic regression analyses were used to assess the value of lactate clearance for predicting death. Result: Among 4425 acute pancreatitis patients, 3040 patients were diagnosed with moderate or severe acute pancreatitis, and 1028 patients had initial lactate measured. Finally, 390 patients who had initial and 24-hour repeat lactate data were included in the study. Patients who had elevated initial lactate had poor outcomes, and 51 patients in the initial elevated lactate group died. In the lactate normalization group analysis, 293 patients had 24-hour lactate normalization; compared with patients in the nonnormalization group, they had a lower rate of mortality (12.6% vs. 33%). In the lactate clearance group analysis, 70 (21.9%) patients had a low clearance after 24 hours; compared with patients in the high clearance group, they had a higher rate of developing persistent multiorgan failure (P = 0.045), and the incidence of death was higher (15% vs. 28.6%, P = 0.007). Multivariate logistic analysis showed that 24-hour lactate clearance (OR: 2.007; 95% CI:1.032-3.903, P = 0.04), elevated initial lactate (OR: 2.011; 95% CI:1.023-3.953, P = 0.043), blood urea nitrogen (OR: 2.316; 95% CI:1.061-5.056, P = 0.035), and white blood count (OR: 1.982; 95% CI:1.026-3.829, P = 0.042) were independent predictors of hospital mortality. Conclusion: The 24-hour clearance of lactate is a reliable marker to predict the outcome of moderate and severe acute pancreatitis, and low lactate clearance may indicate that the patient's condition will worsen, requiring aggressive treatments to improve patient outcomes.
Asunto(s)
Ácido Láctico , Pancreatitis , Humanos , Pronóstico , Tasa de Depuración Metabólica , Enfermedad Aguda , BiomarcadoresRESUMEN
Cholinergic nerves are widely distributed throughout the human body and participate in various physiological activities, including sensory, motor, and visceral activities, through cholinergic signaling. Cholinergic signaling plays an important role in pancreatic exocrine secretion. A large number of studies have found that cholinergic signaling overstimulates pancreatic acinar cells through muscarinic receptors, participates in the onset of pancreatic diseases such as acute pancreatitis and chronic pancreatitis, and can also inhibit the progression of pancreatic cancer. However, cholinergic signaling plays a role in reducing pain and inflammation through nicotinic receptors, but enhances the proliferation and invasion of pancreatic tumor cells. This review focuses on the progression of cholinergic signaling and pancreatic diseases in recent years and reveals the role of cholinergic signaling in pancreatic diseases.
Asunto(s)
Pancreatitis , Enfermedad Aguda , Colinérgicos , Humanos , Páncreas/inervación , Receptores MuscarínicosRESUMEN
Antibiotic-associated diarrhea (AAD) is a common morbidity caused by antibiotic use and is characterized by the dysbiosis of the gut microbiota. Several clinical trials have shown that probiotics can prevent AAD. This study aimed at investigating the effects of Lacidophilin tablets (LB), yogurt (YG), and bifid triple viable capsules (BT) on the gut microbiota of mice with AAD. Mice with diarrhea were randomly allocated to treatment groups or the control group and were treated with either LB, YG, BT, or vehicle control. The body weight, diarrhea scores, cecum index, and cecal length were determined. Fecal samples of all mice were analyzed using 16S rRNA high-throughput sequencing. The results showed that LB, YG, and BT significantly decreased the diarrhea scores and inhibited increases in the cecum index and cecal length induced by AAD. In addition, they significantly changed the composition and richness of the gut microbiota. Specifically, they increased the abundance of the phylum Firmicutes and decreased the abundance of the phyla Bacteroidetes and the family Bacteroidaceae. Treatment with LB and YG also decreased the abundance of the phylum Proteobacteria and only LB could mediate the reduced levels of Lactobacillaceae in AAD mice. At the genus level, YG and BT treatment decreased the abundance of Bacteroides or Parasutterella. To our surprise, only LB treatment dramatically increased the abundance of Lactobacillus and decreased that of potential pathogens, such as Bacteroides, Parabacteroides, and Parasutterella, to almost normal values. Our findings indicate that LB, YG, and BT ameliorated diarrhea by regulating the composition and structure of the gut microbiota and that LB plays an important role in regulating the gut microbiota.
RESUMEN
In this paper, a node splitting optimized canonical correlation forest algorithm for sea fog detection is proposed by using active and passive satellites. The traditional canonical correlation forest (CCF) algorithm insufficiently accounts for the spectral characteristics and the reliability of each classifier during integration. To deal with the problem, the information gain rate of node entropy is used as the splitting criterion, and the spectral characteristics of clouds and fogs are also combined into the model generation process. The proposed algorithm was verified using the meteorological station data and compared with five state-of-the-art algorithms, which demonstrated that the algorithm has the best performance in sea fog detection and can identify mist better.
Asunto(s)
Pancreatitis Crónica , Animales , Humanos , Ratones , Ratones Transgénicos , Mutación , Tripsina/genética , Tripsinógeno/genéticaRESUMEN
BACKGROUND: Intestinal dysfunction is a common complication of acute pancreatitis. MiR155 may be involved in the occurrence and development of intestinal dysfunction mediated by acute pancreatitis, but the specific mechanism is not clear. AIMS: To investigate the effect of miR155 on severe acute pancreatitis (SAP)-associated intestinal dysfunction and its possible mechanism in a mice model. METHODS: In this study, SAP mice model was induced by intraperitoneal injection of caerulein and LPS in combination. Adeno-associated virus (AAV) was given by tail vein injection before the SAP model. The pancreatic and intestinal histopathology changes were analyzed. Cecal tissue was collected for 16S rRNA Gene Sequencing. Intestinal barrier proteins ZO-1 and E-cad were measured by Immunohistochemistry Staining and Western Blot, respectively. Intestinal tissue miR155 and inflammatory factors TNF-α, IL-1ß, and IL-6 were detected by Q-PCR. The expression levels of protein associated with TNF-α and TLR4/MYD88 pathway in the intestinal were detected. RESULTS: In miR155 overexpression SAP group, the levels of tissue inflammatory factor were significantly increased, intestinal barrier proteins were significantly decreased, and the injury of intestinal was aggravated. Bacterial 16S rRNA sequencing was performed, showing miR155 promotes gut microbiota dysbiosis. The levels of TNF-α, TLR4, and MYD88 in the intestinal were detected, suggesting that miR155 may regulate gut microbiota and activate the TLR4/MYD88 pathway, thereby affecting the release of inflammatory mediators and regulating SAP-related intestinal injury. After application of miR155-sponge, imbalance of intestinal flora and destruction of intestinal barrier-related proteins have been alleviated. The release of inflammatory mediators decreased, and the histopathology injury of intestinal was improved obviously. CONCLUSION: MiR155 may play an important role in SAP-associated intestinal dysfunction. MiR155 can significantly alter the intestinal microecology, aggravated intestinal inflammation through TLR4/MYD88 pathway, and disrupts the intestinal barrier in SAP mice.
Asunto(s)
MicroARNs , Pancreatitis , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Humanos , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/complicaciones , Pancreatitis/metabolismo , ARN Ribosómico 16S/genética , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Contamination of rice by cadmium (Cd) is threatening a large population in China. In this study, we report that soaking rice grains in a hydrochloric acid (HCl) solution can remove Cd to a desirable extent. The results indicated that the degree of Cd removal was up to 45%â¼85% at different soaking times and concentrations of HCl (0.06 M â¼ 0.18 M), which was found to be logarithmically correlated with the reaction time at the optimized liquid-solid ratio of 1:2. Three HCl concentration-dependent mathematical models were established, which revealed various optimal soaking conditions depending on the initial Cd contamination. Four Cd-contaminated rice grain samples with different degrees of contamination were then tested based on the mathematical models, and the final Cd content was reduced to an acceptable extent. Moreover, the physicochemical and food properties of rice flours and rice grains after Cd removal were evaluated to highlight their potential applications.
Asunto(s)
Oryza , Contaminantes del Suelo , Cadmio/análisis , Grano Comestible/química , Estructuras de las Plantas/química , Suelo , Contaminantes del Suelo/análisisRESUMEN
Hyperstimulation of the cholecystokinin 1 receptor (CCK1R), a G protein-coupled receptor (GPCR), in pancreatic acinar cells is commonly used to induce pancreatitis in rodents. Human pancreatic acinar cells lack CCK1R but express cholinergic receptor muscarinic 3 (M3R), another GPCR. To test whether M3R activation is involved in pancreatitis, a mutant M3R was conditionally expressed in pancreatic acinar cells in mice. This mutant receptor loses responsiveness to its native ligand, acetylcholine, but can be activated by an inert small molecule, clozapine-N-oxide (CNO). Intracellular calcium and amylase were elicited by CNO in pancreatic acinar cells isolated from mutant M3R mice but not WT mice. Similarly, acute pancreatitis (AP) could be induced by a single injection of CNO in the transgenic mice but not WT mice. Compared with the cerulein-induced AP, CNO caused more widespread acinar cell death and inflammation. Furthermore, chronic pancreatitis developed at 4 weeks after 3 episodes of CNO-induced AP. In contrast, in mice with 3 recurrent episodes of cerulein-included AP, pancreas histology was restored in 4 weeks. Furthermore, the M3R antagonist ameliorated the severity of cerulein-induced AP in WT mice. We conclude that M3R activation can cause the pathogenesis of pancreatitis. This model may provide an alternative approach for pancreatitis research.
Asunto(s)
Células Acinares/metabolismo , Regulación de la Expresión Génica , Pancreatitis/genética , ARN/genética , Receptor Muscarínico M3/genética , Células Acinares/patología , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Ratones , Ratones Mutantes , Ratones Transgénicos , Pancreatitis/metabolismo , Pancreatitis/patología , Receptor Muscarínico M3/biosíntesis , Transducción de SeñalRESUMEN
BACKGROUND: Identification of patients at risk for persistent organ failure (POF) early in the course of acute pancreatitis (AP) is critical for early intervention. Heparin-binding protein (HBP) levels are closely related to inflammation. Therefore, we investigated the relationship between HBP levels and POF in patients with AP. METHODS: This observational cohort study analyzed 66 patients with AP and 14 healthy volunteers between June 2019 and December 2019. Baseline characteristics, laboratory data, and severity scores of patients with different degrees of AP were compared. Levels of HBP were measured by ELISA. Serum HBP levels were analyzed using receiver operating characteristic curves to identify POF in AP. RESULTS: Concentrations of serum HBP in healthy volunteers, MAP, MSAP, and SAP groups were 3.9 (range: 3.4-5) ng/ml, 5.2 (3.9-6.8) ng/ml, 5.9 (4.6-7.7) ng/ml, and 11 (8.0-13.8) ng/ml, respectively. The level of HBP in SAP patients was significantly elevated compared to the other groups (P < 0.01). HBP levels ≥ 7 ng/ml showed a specificity of 74%, a sensitivity of 90%, and an AUC of 0.82 for predicting POF. CONCLUSIONS: HBP levels in patients with POF were significantly elevated. HBP is a useful marker for predicting severe AP.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/sangre , Pancreatitis/sangre , Pancreatitis/patología , Enfermedad Aguda , Adulto , Biomarcadores/sangre , Proteínas Sanguíneas , Estudios de Cohortes , Hospitalización , Humanos , Persona de Mediana EdadRESUMEN
Human immunodeficiency virus-1 (HIV-1) exhibits high diversity and complexity in China, challenging the disease surveillance and antiretroviral therapy. Between July 1, 2014 and January 30, 2017, we investigated the profiles of HIV-1 infection stages, genotype distribution and drug resistance mutations (DRMs) using plasma samples from HIV Western blot (WB) confirmed blood donors from five Chinese blood centers (Chongqing, Guangxi, Luoyang, Mianyang, and Urumqi). HIV pol regions consisted of whole protease and partial reverse transcriptase were genotyped and analyzed for DRMs. Lag-Avidity testing was performed to identify the infection stages. Of the 356 HIV-1 WB positive samples tested by Lag-avidity assay, 19.1% (68/356) were recent infections. Genotyping on 356 amplified sequences presented the subtype distributions as following: CRF07_BC (65.7%), CRF08_BC (7.3%), CRF01_AE (19.1%), B (4.2%), CRF55_01B (3.1%), CRF59_01B (0.3%) and CRF68_01B (0.3%). No significant difference in genotype distribution was observed between recent and long-term infections. 48 DRMs were identified from 43 samples, indicating a drug resistance prevalence of 12.1% (43/356), which include seven protease inhibitors (PIs) accessory DRMs (Q58E, L23I and I84M), two PIs major DRMs (M46I, M46L), seven nucleoside RT inhibitors DRMs (D67N, K70Q, K219R and M184L), and 32 non-nucleoside RT inhibitors DRMs (K103N, V179E, K238N, V179D, E138G, G190E, A98G, Y188D and E138A). In addition, we had also identified CRFs from the 01B subtype including CRF55_01B (3.1%), CRF59_01B (0.3%) and CRF68_01B (0.3%). As an important part of the continuous monitoring of HIV-1 circulating strains among blood donors, our findings were expected to contribute to the comprehensive AIDS control and development of proper diagnostics for HIV-1 in China.
Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Farmacorresistencia Viral/genética , Infecciones por VIH/epidemiología , VIH-1/genética , Adulto , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , China/epidemiología , Genotipo , Técnicas de Genotipaje , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Proteasa del VIH/genética , VIH-1/aislamiento & purificación , Humanos , Mutación , Filogenia , ARN Viral/genética , ARN Viral/aislamiento & purificación , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
BACKGROUND: The incidence of acute pancreatitis (AP) in ageing patients has increased in recent years, and results regarding the clinical outcomes of these patients are controversial. The aim of this study was to compare the clinical outcomes of AP in ageing patients over 60 years old. METHODS: Eighty patients aged ≥80 years (oldest group) were compared to 393 patients aged 60 to 79 years (older group). The clinical course and biochemical and radiological data were evaluated. The primary endpoints were mortality rate, intensive care unit (ICU) admission rate and in-hospital length of stay (LOS). The secondary endpoints were the incidence of operative treatment and complications of AP. RESULTS: Abdominal pain (61.3% vs 46.3%, P=0.013) was less common in the oldest group. Jaundice (17.5% vs 8.9%, P=0.021) and dyspnoea (26.3% vs 11.5%, P=0.001) were more obvious in the oldest group than in the older group. The mean BMI was lower in the oldest group than in the older group (21.07±3.18 vs 22.36±2.89, P = 0.001). Age over 80 years (P=0.011) and organ failure (P<0.05) were independent risk factors for mortality. More severe AP (P=0.001), abdominal pain (P=0.033) and organ failure (P<0.05) were associated with the ICU admission rate. Age over 80 years (P=0.001), more severe AP (P=0.001), female sex (P=0.018), jaundice (P=0.038), operative treatment (P<0.05) and organ failure (P<0.05) were risk factors for increased LOS. CONCLUSION: The oldest group had a higher death rate and longer LOS than the older group. More attention should be given to the clinical symptoms of this frail population. We propose that more comprehensive and goal-directed attendant diagnostic procedures should be performed to detect the disease early and to improve the outcomes of ageing patients.
Asunto(s)
Pancreatitis/diagnóstico , Pancreatitis/fisiopatología , Índice de Severidad de la Enfermedad , Anciano , Femenino , Humanos , Incidencia , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Pancreatic endocrine insufficiency after acute pancreatitis (AP) has drawn increasing attention in recent years. AIM: To assess the impact of risk factors on the development of pancreatic endocrine insufficiency after AP. METHODS: This retrospective observational long-term follow-up study was conducted in a tertiary hospital. Endocrine function was evaluated by the oral glucose tolerance test. The data, including age, sex, body mass index, APACHE II score, history of smoking and drinking, organ failure, pancreatic necrosis, debridement of necrosis (minimally invasive and/or open surgery), and time interval, were collected from the record database. RESULTS: A total of 361 patients were included in the study from January 1, 2012 to December 30, 2018. A total of 150 (41.6%) patients were diagnosed with dysglycemia (including diabetes mellitus and impaired glucose tolerance), while 211 (58.4%) patients had normal endocrine function. The time intervals (mo) of the above two groups were 18.73 ± 19.10 mo and 31.53 ± 27.27 mo, respectively (P = 0.001). The morbidity rates of pancreatic endocrine insufficiency were 46.7%, 28.0%, and 25.3%, respectively, in the groups with different follow-up times. The risk factors for pancreatic endocrine insufficiency after AP were severity (odds ratio [OR] = 3.489; 95% confidence interval [CI]: 1.501-8.111; P = 0.004) and pancreatic necrosis (OR = 4.152; 95%CI: 2.580-6.684; P = 0.001). CONCLUSION: Pancreatic necrosis and severity are independent risk factors for pancreatic endocrine insufficiency after AP. The area of pancreatic necrosis can affect pancreatic endocrine function.
Asunto(s)
Pancreatitis Aguda Necrotizante , Enfermedad Aguda , Estudios de Seguimiento , Humanos , Pancreatitis Aguda Necrotizante/diagnóstico , Pancreatitis Aguda Necrotizante/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Hepatitis C virus (HCV) genotype (GT) distribution in China shows significant geographical and demographic difference. As a routinely tested virus in Chinese blood bank systems, rare molecular epidemiology research in blood donors is reported. Our purpose is to investigate the HCV GT/subtypes distribution, phylogenetic analysis and population genetics in Chinese blood donors. Anti-HCV screen positive samples and donor demographics were collected. HCV Core and E1 gene fragments were amplified by RT-PCR, followed by sequencing and phylogenetic analysis to determine HCV GTs/subtypes using MEGA 7.0. The population genetics were performed using Arlequin v3.0 and Beast v1.10.4. SPSS Statistics 17.0 software was used to analyze the correlation between HCV GTs/subtypes distribution and demographic characteristics. 419 and 293 samples based on Core and E1 gene respectively were successfully amplified. HCV la, lb, 2a, 3a, 3b, 6a, 6e and 6n were found, and the corresponding proportions were 0.66% (3/455), 58.68% (267/455), 17.80% (81/455) and 5.05% (23/455), 3.52% (16/455), 12.31% (56/455), 0.88% (4/455) and 0.66% (3/455). Samples from Guangxi showed the most abundant genetic diversity with 8 subtypes were found. The number of haplotypes in HCV-1b is higher than 2a and 6a. The negative Tajima's D and Fu's Fs values of HCV-1b, 2a and 6a suggested the population expansion of those HCV subtypes. The distribution of HCV GT showed significant statistical difference by age and ethnicity. Conclusion: An abundance of HCV genetic diversity was found in Chinese blood donors with mainly 1b and then 2a subtype. There were significant geographical and demographic differences in HCV GTs/subtypes among Chinese blood donors. HCV subtype 1b has stronger viability and HCV subtype 6a has experienced significant expansion.