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Background: Severe acute pancreatitis (SAP) is an inflammatory disorder affecting the gastrointestinal system. Intestinal injury plays an important role in the treatment of severe acute pancreatitis. In this study, we mainly investigated the role of S1PR2 in regulating macrophage pyroptosis in the intestinal injury of severe acute pancreatitis. Methods: The SAP model was constructed using cerulein and lipopolysaccharide, and the expression of S1PR2 was inhibited by JTE-013 to detect the degree of pancreatitis and intestinal tissue damage in mice. Meanwhile, the level of pyroptosis-related protein was detected by western blot, the level of related mRNA was detected by PCR, and the level of serum inflammatory factors was detected by ELISA. In vitro experiments, LPS+ATP was used to construct the pyroptosis model of THP-1. After knockdown and overexpression of S1PR2, the pyroptosis proteins level was detected by western blot, the related mRNA level was detected by PCR, and the level of cell supernatant inflammatory factors were detected by ELISA. A rescue experiment was used to verify the sufficient necessity of the RhoA/ROCK pathway in S1PR2-induced pyroptosis. Meanwhile, THP-1 and FHC were co-cultured to verify that cytokines released by THP-1 after damage could regulate FHC damage. Results: Our results demonstrated that JTE-013 effectively attenuated intestinal injury and inflammation in mice with SAP. Furthermore, we observed a significant reduction in the expression of pyroptosis-related proteins within the intestinal tissue of SAP mice upon treatment with JTE-013. We confirmed the involvement of S1PR2 in THP-1 cell pyroptosis in vitro. Specifically, activation of S1PR2 triggered pyroptosis in THP-1 cells through the RhoA/ROCK signaling pathway. Moreover, it was observed that inflammatory factors released during THP-1 cell pyroptosis exerted an impact on cohesin expression in FHC cells. Conclusion: The involvement of S1PR2 in SAP-induced intestinal mucosal injury may be attributed to its regulation of macrophage pyroptosis.
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Modelos Animales de Enfermedad , Macrófagos , Pancreatitis , Piroptosis , Receptores de Esfingosina-1-Fosfato , Animales , Ratones , Humanos , Macrófagos/metabolismo , Macrófagos/inmunología , Pancreatitis/metabolismo , Pancreatitis/inmunología , Pancreatitis/patología , Pancreatitis/inducido químicamente , Receptores de Esfingosina-1-Fosfato/metabolismo , Receptores de Esfingosina-1-Fosfato/genética , Masculino , Transducción de Señal , Ratones Endogámicos C57BL , Proteína de Unión al GTP rhoA/metabolismo , Células THP-1 , Quinasas Asociadas a rho/metabolismo , Quinasas Asociadas a rho/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Intestinos/patología , Intestinos/inmunología , Citocinas/metabolismo , Lipopolisacáridos , Pirazoles , PiridinasRESUMEN
OBJECTIVE: To compare the effect of balanced multielectrolyte solutions(BMES) versus normal saline(NS) for intravenous fluid on chloride levels and clinical outcomes.in patients with predicted severe acute pancreatitis (pSAP). SUMMARY BACKGROUND DATA: Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown. METHODS: In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (APACHE II score ≥8 and C-reactive protein >150 mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase(Sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day3. Secondary endpoints included a composite of clinical and laboratory measures. RESULTS: Overall, 259 patients were enrolled from eleven sites to receive NS(n=147) or BMES(n=112). On trial day3, the mean chloride level was significantly lower in patients who received BMES(101.8 mmol/L(SD4.8) versus 105.8 mmol/L(SD5.9), difference -4.3 mmol/L [95%CI -5.6 to -3.0 mmol/L];P<0.001). For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome(19/112,17.0% versus 43/147,29.3%, P=0.024) and increased organ failure-free days (3.9 d(SD2.7) versus 3.5days(SD2.7), P<0.001) by trial day7. They also spent more time alive and out of ICU(26.4 d(SD5.2) versus 25.0days(SD6.4), P=0.009) and hospital(19.8 d(SD6.1) versus16.3days(SD7.2), P<0.001) by trial day30. CONCLUSIONS: Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits(Trial registration number: ChiCTR2100044432).
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Radiotherapy (RT) has been reported to induce abscopal effect in advanced hepatocellular carcinoma (HCC), but such phenomenon was only observed in sporadic cases. Here, we demonstrated that subcutaneous administration of Toll-like receptor 3 (TLR3) agonist poly(I:C) could strengthen the abscopal effect during RT through activating tumor cell ferroptosis signals in bilateral HCC subcutaneous tumor mouse models, which could be significantly abolished by TLR3 knock-out or ferroptosis inhibitor ferrostatin-1. Moreover, poly(I:C) could promote the presentation of tumor neoantigens by dendritic cells to enhance the recruitment of activated CD8+ T cells into distant tumor tissues for inducing tumor cell ferroptosis during RT treatment. Finally, the safety and feasibility of combining poly(I:C) with RT for treating advanced HCC patients were further verified in a prospective clinical trial. Thus, enhancing TLR3 signaling activation during RT could provide a novel strategy for strengthening abscopal effect to improve the clinical benefits of advanced HCC patients.
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Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Poli I-C , Receptor Toll-Like 3 , Receptor Toll-Like 3/metabolismo , Receptor Toll-Like 3/agonistas , Animales , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patología , Humanos , Ratones , Poli I-C/farmacología , Masculino , Femenino , Línea Celular Tumoral , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Ratones Noqueados , Persona de Mediana EdadRESUMEN
BACKGROUND AND AIMS: Postoperative adjuvant transcatheter arterial chemoembolization (TACE) can prevent recurrence of hepatocellular carcinoma (HCC) in certain patients. This study aimed to identify the potential beneficiaries of adjuvant TACE. METHODS: 477 patients who underwent curative resection for HCC were enrolled in this retrospectively cohort study. The trajectory of the prognostic nutritional index (PNI) during the perioperative period was fitted using a latent-class growth mixed model. The association between adjuvant TACE and recurrence-free survival in each PNI group was assessed using the Kaplan-Meier curve. Furthermore, Cox regression analysis was conducted to identify the risk factors for early recurrence after adjuvant TACE and develop a nomogram model. RESULTS: Patients in the PNI group III had a high risk of recurrence and could benefit from adjuvant TACE (P = 0.009). The prognostic prediction model for adjuvant TACE (PAT) incorporated eight variables (PNI, tumor size, tumor number, microvascular invasion, sex, aspartate aminotransferase, gamma-glutamyl transferase, and degree of differentiation). Patients with PAT score >330 and 235-330 had significantly higher recurrence rates than those with PAT score <235 (P < 0.001). CONCLUSION: PNI may help guide the selection of adjuvant TACE beneficiaries. PAT demonstrated a high accuracy in predicting the prognosis of patients who underwent postoperative TACE.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Evaluación Nutricional , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Anciano , Estudios de Cohortes , Resultado del Tratamiento , NomogramasRESUMEN
Clinically, a considerable number of non-small cell lung cancer (NSCLC) patients are unable to receive or resist chemotherapy, and the efficacy of non-chemotherapy treatment strategies based on anti-angiogenic agents combined with immune checkpoint blockade is still unsatisfactory. Neoantigen vaccine, based on personalized tumor DNA mutations, could elicit tumor specific T cell infiltration into the tumor site, exerting potent anti-tumor efficacy. Here, we evaluated the feasibility and safety of a new antitumor strategy by adding neoantigen vaccine to the regimen of bevacizumab and anti-PD-1 antibody. Firstly, 7 novel immunogenic neoantigen peptides were identified and developed for neoantigen vaccine (LLCvac), which can elicit strong antitumor immune response in vivo. Then, in orthotopic lung cancer model, LLCvac further combining with bevacizumab and anti-PD-1 antibody exerted a stronger antitumor effect, exhibiting significant decrease of tumor volume without obvious toxicity. Furthermore, tumor immune microenvironment assessment also showed that the proportion of neoantigen-specific T cells in blood could be induced dramatically by the combined therapy. And a large amount of neoantigen-specific Ki67-positive CD8+ T cells were found in tumor tissues, which infiltrated tumor tissues effectively to kill tumor cells expressing identified neoantigens. Overall, these results suggested that this combined therapy could safely induce robust antitumor efficacy, serving as an effective chemotherapy-free strategy for NSCLC treatment.
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Vacunas contra el Cáncer , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígenos de Neoplasias , Bevacizumab/uso terapéutico , Vacunas contra el Cáncer/farmacología , Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Linfocitos T CD8-positivos , Neoplasias Pulmonares/tratamiento farmacológico , Microambiente TumoralRESUMEN
[This corrects the article DOI: 10.3389/fphar.2023.1090261.].
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BACKGROUND Acute pancreatitis, a sudden inflammation of the pancreas, can result in severe complications. The presence and volume of ascites, an abnormal accumulation of fluid in the abdomen, has been linked to disease severity. Our study investigates ascites volume, quantified via abdominal CT scans, as a potential predictive tool for disease severity. MATERIAL AND METHODS In this retrospective analysis, patients diagnosed with acute pancreatitis were evaluated. Patients were categorized into groups with and without ascites, with comparisons made regarding clinical characteristics. We further compared the mean ascitic volume against various outcome parameters in patients with ascites. Ascites volume and other predictive systems were assessed through receiver operating characteristic (ROC) curves, with the area under the ROC curve (AUC) for different predictive systems being analyzed. RESULTS The ascites group had higher severity scores and related serological indexes (P<0.05 for all). Among patients with ascites, a significant correlation was observed between ascites volume and outcome parameters (P<0.05 for all). The area under the ROC curve for predicting severe acute pancreatitis was 0.896, with 93% sensitivity and 79% specificity. Ascites volume yielded the highest diagnostic odds ratio (53.1; 95% confidence interval: 13.2,199.6). CONCLUSIONS Early-stage acute pancreatitis patients with ascites are indicative of severe illness and poor prognosis. An increase in ascites volume correlates with adverse clinical outcomes, thus highlighting the significance of ascites volume as a prognostic marker. This underscores the importance of abdominal CT in measuring ascites volume to predict disease severity.
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Ascitis , Pancreatitis , Humanos , Ascitis/diagnóstico por imagen , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Enfermedad Aguda , Pancreatitis/complicaciones , Tomografía Computarizada por Rayos X/métodos , Abdomen , Curva ROC , Pronóstico , Valor Predictivo de las PruebasRESUMEN
ABSTRACT: Oxygen-carrying plasma, a new type of colloid substitute, is composed of hydroxyethyl starch and acellular hemoglobin-based oxygen carriers. It can supplement colloidal osmotic pressure and rapidly improve the body's oxygen supply. The resuscitation effect of the new oxygen-carrying plasma in animal shock models is better than that of hydroxyethyl starch or hemoglobin-based oxygen carriers alone. It can reduce the histopathological damage and mortality associated with severe acute pancreatitis, and it is expected to become an interesting treatment method for severe acute pancreatitis. This article reviews the characteristics of the new oxygen-carrying plasma, its role in fluid resuscitation, and its application prospects in the treatment of severe acute pancreatitis.
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Pancreatitis , Animales , Pancreatitis/patología , Enfermedad Aguda , Derivados de Hidroxietil Almidón , Fluidoterapia/métodos , Oxígeno , Hemoglobinas/uso terapéuticoRESUMEN
BACKGROUND: Infected pancreatic necrosis (IPN) accounts for 30% mortality in severe acute pancreatitis (SAP). Early prediction of IPN occurrence is critical for prophylactic measures to be taken. This study aimed to evaluate the predicting value for IPN of combined markers at early stages of SAP. METHODS: The clinical records of 324 SAP patients admitted within 48 h after disease onset were retrospectively analyzed. As potential predictors, the neutrophil to lymphocyte ratio (NLR), blood procalcitonin (PCT) concentration on the 1st, 4th, and 7th day post admission, as well as modified computerized tomography severity index (MCTSI) on the 5-7th day post admission, were extracted. Correlations between these features with IPN were analyzed using logistic regression, and predictive values were estimated using the receiver operating characteristic curve analyses. RESULTS: NLR, PCT, body mass index, and MCTSI were significantly higher in the IPN group (p < 0.001) compared to the control, among which NLR, PCT, and MCTSI were identified as independent predictors for IPN in logistic regression model. Combination of these parameters yielded significant predicting values with an area under curve of 0.92, sensitivity of 97.2%, and specificity of 77.2% in receiver operating characteristic curve analysis. CONCLUSION: Combination of NLR, PCT, MCTSI might facilitate the prediction of IPN occurrence in SAP patients.
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Pancreatitis Aguda Necrotizante , Humanos , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Polipéptido alfa Relacionado con Calcitonina , Enfermedad Aguda , Neutrófilos , Estudios Retrospectivos , Curva ROC , Linfocitos , Tomografía Computarizada por Rayos X , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
Background: In this study, we examined the functions and mechanisms by which naringenin protects against SAP (severe acute pancreatitis)-related intestinal injury by modulating the AhR/NLRP3 signaling pathway. Material and methods: Fifteen healthy male C57BL/6 mice were randomly divided into SAP (n = 12) and normal (n = 3) groups. Mice in the SAP group received caerulein and lipopolysaccharide intraperitoneal injections and were then randomly assigned to the SAP, NAR, CH223191, and Dexamethasone (DEX) groups. Pathological changes in the pancreatic and intestinal mucosa were observed by Hematoxylin & Eosin (H&E) staining. In vitro, RAW264.7 cells were exposed to lipopolysaccharide and treated with naringenin. The levels of NLRP3, AhR, IL-1ß, TNF, and IL-6 in the SAP model and RAW264.7 cells were evaluated by enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. The nuclear translocation of AhR was shown by immunofluorescence. AutoDockTools was used to predict the conformations of naringenin-AhR binding, and PyMol 2.4 was used to visualize the conformations. Results: Mouse pancreatic and intestinal injury was alleviated by treatment with naringenin. Naringenin inhibited the activation of the NLRP3 inflammasome and inhibited damage to intestinal tight junctions. Moreover, naringenin increased AhR nuclear translocation and activated the AhR pathway. Conclusion: Naringenin can reduce SAP-associated intestinal injury by inhibiting the activation of the NLRP3 inflammasome via the AhR signaling pathway.
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Background: Iron overload is frequently observed in non-alcoholic fatty liver disease (NAFLD). Transferrin receptor 2 (TFR2) is an important key factor in iron regulation. We aimed to investigate whether TFR2 single nucleotide polymorphisms (SNPs) contribute to susceptibility to NAFLD in a Chinese Han population. Methods: Five tag SNPs (rs10247962, rs4434553, rs2075672, rs1052897, and rs3757859) in the TFR2 gene were selected and genotyped in a case-control study on participants who visited two affiliated hospitals of Fujian Medical University between June 2011 and August 2017. Propensity score matching and inverse probability of treatment weighting analyses were used to verify the risk associated with TFR2 SNPs. Results: Logistic regression analyses suggested that subjects with the rs4434553 GA or GG genotype had a lower risk of NAFLD than those carrying the AA genotype (odds ratio = 0.630, 95% confidence interval = 0.504-0.788). Moreover, the rs4434553 GA or GG genotype was negatively correlated with body mass index, hepatic steatosis index, and serum ferritin (b = -0.363, P = 0.008; b = -1.040, P = 0.009; b = -35.258, P = 0.015, respectively), and positively associated with serum hepcidin level (b = 35.308, P < 0.001). Moreover, rs10247962 and rs1052897 had multiplicative interactions with age in relation to the risk of NAFLD (P for interactions, 0.041 and 0.034, respectively). The cumulative effects of the rs10247962, rs1052897, and rs4434553 SNPs were positively associated with the risk of NAFLD (adjusted P trend = 0.012). Conclusions: In this Chinese Han population, the rs4434553 polymorphism in TFR2 may be an independent influencing factor associated with the susceptibility to NAFLD. The ageing effect on the development of NAFLD may be inhibited by SNPs rs10247962 and rs1052897.
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PURPOSE: Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP. METHODS: We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission. RESULTS: A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI - 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%). CONCLUSION: The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.
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Pancreatitis Aguda Necrotizante , Humanos , Enfermedad Aguda , Método Doble Ciego , Pancreatitis Aguda Necrotizante/complicaciones , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Resultado del TratamientoRESUMEN
This publication has been retracted by the Editor due to the identification of non-original figure images that raise concerns regarding the credibility and originality of the study. Reference: You-Dong Wan, Rui-Xue Zhu, Zhong-Zheng Bian, Xin-Ting Pan. Improvement of Gut Microbiota by Inhibition of P38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Rats with Severe Acute Pancreatitisy. Med Sci Monit, 2019; 25: 4609-4616. DOI: 10.12659/MSM.914538.
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BACKGROUND Acute pancreatitis (AP) is a common acute abdominal disease. Rapid evaluation of the severity is important for AP prognosis and treatment. Free triiodothyronine (fT3) level is associated with the prognosis of AP patients. This study aimed to investigate the fT3 level in patients with acute pancreatitis; early warning signs of inflammation, including interleukin-6 (IL-6) and interleukin-10 (IL-10); and the correlation of fT3 level with illness severity. MATERIAL AND METHODS Enrolled AP patients (N=312) were divided into an SAP group (N=92) and a non-SAP group (N=220) according to the Revision of Atlanta classification. Blood or tissue samples and baseline clinical characteristics were recorded. The t test and chi-square test were used to evaluate differences between the 2 groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to investigate protective factors. One-way repeated measures analysis of variance was used to evaluate the prognosis of SAP patients. RESULTS In our study, compared with APACHII score (AUC 0.829 [95% CIs 0.769-0.889]) and Ranson score (AUC 0.629 [95% CIs 0.542-0.715]), our predictive model (AUC 0.918 [95% CIs 0.875-0.961]) showed better prognostic performance in predicting poor patient outcomes. In the SAP group, changes in fT3 level were significantly associated with prognosis (P<0.05). CONCLUSIONS The predictive model can improve the diagnostic accuracy and prediction of the severity of disease. FT3 level could be used as an independent risk factor to predict the mortality of SAP patients.
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Interleucina-10/sangre , Interleucina-6/sangre , Pancreatitis/sangre , Pancreatitis/fisiopatología , Triyodotironina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Optimal non-invasive biomarkers for diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD) remain to be identified. AIMS: To identify potential DNA methylation biomarkers for NAFLD. METHODS: Genome-wide DNA methylation profiling was performed to identify differentially methylated CpG sites in peripheral blood leukocytes. Differentially methylated regions were validated using the MassCLEAVE assay. The expression levels of candidate genes were explored by Gene Expression Omnibus database. RESULTS: The hypomethylation of PRKCE CpG 4.5 and CpG 18.19 was associated with nonalcoholic fatty liver (NAFL), the odds ratio (OR) and 95% confidence interval (CI) were 0.129 (0.026-0.639) and 0.231 (0.069-0.768). The methylation level of CpG 1.2 and average methylation level of SEC14L3 were correlated with NAFL, with OR (95% CI) being 0.283 (0.093-0.865) and 0.264 (0.087-0.799). PRKCE CpG 4.5 and cg17802464 of SEC14L3 were correlated with body mass index, waist circumference, total triglyceride, high-density lipoprotein cholesterol, alanine aminotransferase and aspartate aminotransferase. All selected datasets showed high expression levels of PRKCE and SEC14L3 in patients with NAFLD. CONCLUSIONS: Our findings suggest that the hypomethylation of PRKCE and SEC14L3 promoters represent attractive biomarkers for NAFLD. Further studies are warranted to validate these biomarkers as molecular tools for diagnosis of NAFLD and therapeutic targets.
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Proteínas Portadoras/metabolismo , Enfermedad del Hígado Graso no Alcohólico , Alanina Transaminasa/metabolismo , Biomarcadores , Islas de CpG/genética , Metilación de ADN , Humanos , Proteína Quinasa C-epsilon/genética , Proteína Quinasa C-epsilon/metabolismoRESUMEN
Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration. Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment. Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy. Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).
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BACKGROUND: Non-alcohol fatty liver disease (NAFLD) is the most common liver disease and an unhealthy lifestyle can lead to an increased risk of NAFLD. The present study aims to evaluate the association of meat consumption with NAFLD risk and liver-related biochemical indexes in middle-aged and elderly Chinese. METHODS: A cross-sectional study was conducted in individuals who were 45 years or older and underwent a physical examination from April 2015 to August 2017 in Southeast China. To evaluate associations between meat intake and NAFLD risk, inverse probability of treatment weighting and subgroup analyses were performed with logistic regressions. Spearman's rank correlation was carried out to examine the relationship between meat consumptions and liver-related biochemical indexes. RESULTS: High consumptions of red meat (28.44-49.74 and > 71.00 g/day) (ORadjusted = 1.948; P < 0.001; ORadjusted = 1.714; P = 0.002) was positively associated with NAFLD risk on inverse probability of treatment weighting analysis, adjusting for smoking, tea intake, weekly hours of physical activity and presence of hypertension, dyslipidemia and diabetes. Exposure-response relationship analysis presented that red meat intake was positively associated with NAFLD risk. Significant associations of red meat intakes with serum levels of γ-glutamyl transferase, alanine transaminase, aspartate aminotransferase, total triglyceride and high-density lipoprotein cholesterol were found (rs = 0.176; P < 0.001; rs = 0.128; P < 0.001; rs = 0.060; P = 0.016; rs = 0.085; P = 0.001; rs = - 0.074; P = 0.003). CONCLUSIONS: These findings suggest that the reduction of meat consumption may decrease NAFLD risk and should warrant further investigations.
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Enfermedad del Hígado Graso no Alcohólico , Anciano , China/epidemiología , Estudios Transversales , Humanos , Carne , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/etiología , Factores de RiesgoRESUMEN
Aortic sinus aneurysms are mainly congenital malformations that can involve the left, right, and noncoronary sinus. Rupture of the noncoronary sinus aneurysms is rare, and its mechanisms and complications are still imperfectly known due to the rarity of this condition. A case of multiple organ dysfunction caused by a ruptured noncoronary sinus aneurysm has been reported.
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Aneurisma de la Aorta , Rotura de la Aorta , Seno Aórtico , Rotura de la Aorta/complicaciones , Rotura de la Aorta/diagnóstico por imagen , Humanos , Insuficiencia Multiorgánica/etiología , Seno Aórtico/diagnóstico por imagenRESUMEN
BACKGROUND Intestinal injury plays a key role in the pathogenesis of severe acute pancreatitis (SAP). In this study, we investigated the protective function of downregulated Gasdermin D (GSDMD) in intestinal damage in a mouse model of severe acute pancreatitis (SAP). MATERIAL AND METHODS Twenty-four healthy male C57BL/6 mice were randomly divided into 4 groups - the NS group, the siRNA-NS group, the SAP group, and the siRNA-SAP group - with 6 mice in each group. SAP was induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide. The pathological changes of pancreatic and the intestinal mucosa and the relative gene and protein expressions in each group were compared, and the levels of GSDMD and serum IL-1ß and IL-18 were evaluated after induction of the SAP model. RESULTS The mice in the SAP group were in more serious condition than those in the siRNA-SAP group, with various degrees of edema and hemorrhage in the intestinal tract. Under an optical microscope, the pathological changes of pancreatic tissue such as edema, inflammatory cell infiltration, and the damage of lobular structural were gradually increased in the SAP group and the siRNA-NS group. In addition, intestinal mucosal damage and intestinal villus breakage were found in the SAP group and the siRNA-NS group, and the latter was lighter than the former. Compared with the SAP group, the level of GSDMD protein expression in the siRNA-SAP group was lower, and the serum levels of IL-1ß and IL-18 were higher in the SAP group and siRNA-SAP group (P<0.05). Immunohistochemical analysis showed the occludin and ZO-1 proteins in the NS group had a strong brown linear signal, while the brown-positive signals were weaker in the siRNA-SAP group and the SAP group. CONCLUSIONS Downregulating GSDMD protein can reduce pancreatitis associated with pyroptosis.