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. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06745-7.
Fe–N co-doped porous carbon (Fe–N–PC) was prepared by a facile one-step pyrolysis strategy using biomass soybean straw as the precursor, which exhibits outstanding electrocatalytic performance for ORR, excellent stability and methanol tolerance.
Long noncoding RNAs (lncRNAs) are a novel class of noncoding RNAs that have emerged as critical regulators and biomarkers in various cancers. Nevertheless, the expression profile and mechanistic function of lncRNAs in cholangiocarcinoma (CCA) remain unclear. Herein, we examined the expression levels of linc00976 in clinical specimens and cell lines using reverse transcription-quantitative PCR. In total, 50 patients with CCA were enrolled to analyze the correlation between linc00976 expression and clinical characteristics of CCA. Loss- and gain-of-function experiments were performed to investigate the biological effects of linc00976 on proliferation, ferroptosis, migration, and invasion of CCA cells in vitro and in vivo. In situ hybridization, RNA immunoprecipitation, bioinformatic databases, RNA pull-down assay, a dual-luciferase reporter assay, mRNA sequencing, chromatin immunoprecipitation–PCR, and rescue experiments were performed to elucidate the underlying mechanisms of linc00976-induced competitive endogenous RNA regulatory networks. We characterized a novel and abundant lncRNA, linc00976, that functions as a pro-oncogenic regulator of CCA progression. Compared with normal controls, linc00976 was dramatically upregulated in CCA tissue samples and cell lines. Patients with CCA exhibiting high linc00976 expression had a highly advanced clinical stage, substantial lymph node metastasis, and poor overall survival. Knockdown of linc00976 significantly repressed proliferation and metastasis and promoted ferroptosis of CCA cells both in vitro and in vivo, whereas linc00976 overexpression exerted the opposite effect. Mechanistically, linc00976 competitively interacted with miR-3202 to upregulate GPX4 expression, thus contributing to the malignant biological behavior of CCA cells. Moreover, we demonstrated that JUND specifically interacts with the linc00976 promoter and activates linc00976 transcription. Accordingly, JUND promotes linc00976 transcription, and linc00976 plays a crucial role in accelerating CCA tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis. These findings suggest that targeting linc00976 may afford a promising therapeutic strategy for patients with CCA.
Clustering analysis is a promising data-driven method for the analysis of functional magnetic resonance imaging (fMRI) data. The huge computation load, however, makes it difficult for the practical use. We use affinity propagation clustering (APC), a new clustering algorithm especially for large data sets to detect brain functional activation from fMRI. It considers all data points as possible exemplars through the minimisation of an energy function and message-passing architecture, and obtains the optimal set of exemplars and their corresponding clusters. Four simulation studies and three in vivo fMRI studies reveal that brain functional activation can be effectively detected and that different response patterns can be distinguished using this method. Our results demonstrate that APC is superior to the k-centres clustering, as revealed by their performance measures in the weighted Jaccard coefficient and average squared error. These results suggest that the proposed APC will be useful in detecting brain functional activation from fMRI data.
ImportancePrevious research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis.ObjectiveTo determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis.Design, Setting, and ParticipantsThe Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022.InterventionsThe patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days.Main Outcomes and MeasuresThe primary outcome was 28-day mortality.ResultsAmong the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group.Conclusions and RelevanceIn this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT03238742
PurposeAnaplastic thyroid carcinoma (ATC) and primary squamous cell carcinoma of the thyroid (PSCCTh) have similar histological findings and are currently treated using the same approaches; however, the characteristics and prognosis of these cancers are poorly researched. The objective of this study was to determine the differences in characteristics between ATC and PSCCTh and establish prognostic models.Patients and MethodsAll variables of patients with ATC and PSCCTh, diagnosed from 2004–2015, were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) database. Percentage differences for categorical data were compared using the Chi-square test. Kaplan-Meier curves, log-rank test, and Cox-regression for survival analysis, and C-index value was used to evaluate the performance of the prognostic models.ResultsAfter application of the inclusion and exclusion criteria, a total of 1164 ATC and 124 PSCCTh patients, diagnosed from 2004 to 2015, were included in the study. There were no differences in sex, ethnicity, age, marital status, or percentage of proximal metastases between the two cancers; however, radiotherapy, chemotherapy, incidence of surgical treatment, and presence of multiple primary tumors were higher in patients with ATC than those with PSCCTh. Further cancer-specific survival (CSS) of patients with PSCCTh was better than that of patients with ATC. Prognostic factors were not identical for the two cancers. Multivariate Cox model analysis indicated that age, sex, radiotherapy, chemotherapy, surgery, multiple primary tumors, marital status, and distant metastasis status are independent prognostic factors for CSS in patients with ATC, while for patients with PSCCTh, the corresponding factors are age, radiotherapy, multiple primary tumors, and surgery. The C-index values of the two models were both > 0.8, indicating that the models exhibited good discriminative ability.ConclusionPrognostic factors influencing CSS were not identical in patients with ATC and PSCCTh. These findings indicate that different clinical treatment and management plans are required for patients with these two types of thyroid cancer.
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