Plasma-derived exosomal long noncoding RNAs of pancreatic cancer patients as novel blood-based biomarkers of disease.

BACKGROUND: Pancreatic cancer (PaCa) is one of the most intractable and fatal malignancies and is associated with the dysregulation of long noncoding RNAs (lncRNAs), which are a large class of noncoding RNAs larger than 200 nt that act as competing endogenous RNAs or sponges for miRNAs to induce tumour biological behaviours. However, their clinical value in treating pancreatic cancer has been poorly explained, but they are essential for improving the prognosis of PaCa patients. METHODS: We analysed the plasma-derived exosomal lncRNA profiles of PaCa patients by using whole-transcriptome sequencing analysis and identified significantly differentially expressed lncRNAs, including LINC01268, LINC02802, AC124854.1, and AL132657.1. In the current study, the expression levels of four plasma-derived exosomal lncRNAs in PaCa plasma were validated via quantitative real-time polymerase chain reaction (qRT‒PCR). The relationship between the expression of the four lncRNAs and the clinicopathological features of patients with PaCa was also evaluated. RESULTS: We demonstrated that exosomal LINC01268, LINC02802, AC124854.1 and AL132657.1 were highly expressed in PaCa plasma compared with those in normal controls; moreover, they were positively correlated with the serum expression of carbohydrate antigen 19-9 (CA19-9). The receiver operating characteristic curves (AUCs) of the four lncRNAs were 0.8421, 0.6544, 0.7190, and 0.6321, and the AUC value of the combination of the four exosomal lncRNAs increased to 0.8476, with a sensitivity of 0.72 and specificity of 0.89. These results suggested that the plasma-derived exosomal genes LINC01268, LINC02802, AC124854.1, and AL132657.1 may be novel diagnostic markers for PaCa. CONCLUSIONS: Our research demonstrated that the plasma-derived exosomal lncRNAs of PaCa patients are novel blood-based biomarkers of disease.

Detection of early neurological deterioration using a quantitative electroencephalography system in patients with large vessel occlusion stroke after endovascular treatment.

BACKGROUND: Early neurological deterioration (END) is a serious complication in patients with large vessel occlusion (LVO) stroke. However, modalities to monitor neurological function after endovascular treatment (EVT) are lacking. This study aimed to evaluate the diagnostic accuracy of a quantitative electroencephalography (qEEG) system for detecting END. METHODS: In this prospective, nested case-control study, we included 47 patients with anterior circulation LVO stroke and 34 healthy adults from different clinical centers in Tianjin, China, from May 2023 to January 2024. Patients with stroke underwent EEG at admission and after EVT. The diagnostic accuracy of qEEG features for END was evaluated by receiver operating characteristic curve analysis, and the feasibility was evaluated by the percentage of artifact-free data and device-related adverse events. RESULTS: 14 patients with stroke had END (29.8%, 95% CI 16.2% to 43.4%), with most developed within 12 hours of recanalization (n=11). qEEG features showed significant correlations with National Institutes of Health Stroke Scale score and infarct volume. After matching, 13 patients with END and 26 controls were included in the diagnostic analysis. Relative alpha power demonstrated the highest diagnostic accuracy for the affected and unaffected hemispheres. The optimal electrode positions were FC3/4 in the unaffected hemisphere, and F7/8 and C3/4 in the affected hemisphere. No device-related adverse events were reported. CONCLUSION: The qEEG system exhibits a high diagnostic accuracy for END and may be a promising tool for monitoring neurological function. The identification of optimal electrode positions may enhance device convenience. CLINICAL TRIAL REGISTRATION: ChiCTR 2300070829.

Nomogram-based geometric and hemodynamic parameters for predicting the growth of small untreated intracranial aneurysms.

Previous studies have shown that the growth status of intracranial aneurysms (IAs) predisposes to rupture. This study aimed to construct a nomogram for predicting the growth of small IAs based on geometric and hemodynamic parameters. We retrospectively collected the baseline and follow-up angiographic images (CTA/ MRA) of 96 small untreated saccular IAs, created patient-specific vascular models and performed computational fluid dynamics (CFD) simulations. Geometric and hemodynamic parameters were calculated. A stepwise Cox proportional hazards regression analysis was employed to construct a nomogram. IAs were stratified into low-, intermediate-, and high-risk groups based on the total points from the nomogram. Receiver operating characteristic (ROC) analysis, calibration curves, decision curve analysis (DCA) and Kaplan-Meier curves were evaluated for internal validation. In total, 30 untreated saccular IAs were grown (31.3%; 95%CI 21.8%-40.7%). The PHASES, ELAPSS, and UIATS performed poorly in distinguishing growth status. Hypertension (hazard ratio [HR] 4.26, 95%CI 1.61-11.28; P = 0.004), nonsphericity index (95%CI 4.10-25.26; P = 0.003), max relative residence time (HR 1.01, 95%CI 1.00-1.01; P = 0.032) were independently related to the growth status. A nomogram was constructed with the above predictors and achieved a satisfactory prediction in the validation cohort. The log-rank test showed significant discrimination among the Kaplan-Meier curves of different risk groups in the training and validation cohorts. A nomogram consisting of geometric and hemodynamic parameters presented an accurate prediction for the growth status of small IAs and achieved risk stratification. It showed higher predictive efficacy than the assessment tools.

Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

The Efficacy of Wearable Cueing Devices on Gait and Motor Function in Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize the efficacy of wearable cueing devices for improving gait and motor function of patients with Parkinson disease (PWP). DATA SOURCES: PubMed, Embase, and Cochrane CENTRAL databases were searched for papers published in English, from inception to October 23, 2022. STUDY SELECTION: Randomized controlled trials focusing on the effects of wearable cueing devices on gait and motor function in PWP were included. DATA EXTRACTION: Two reviewers independently selected articles and extracted the data. The Cochrane Bias Risk Assessment Tool was used to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the quality of evidence. DATA SYNTHESIS: Seven randomized controlled trials with 167 PWP were included in the meta-analysis. Significant effect of wearable cueing devices on walking speed (mean difference [MD]=0.07 m/s, 95% confidence interval [CI]: [0.05, 0.09], P<.00001) was detected; however, after sensitivity analysis, no significant overall effect on walking speed was noted (MD=0.04 m/s, 95% CI: [-0.03, 0.12], P=.25). No significant improvements were found in stride length (MD=0.06 m, 95% CI: [0.00, 0.13], P=.05), the Unified Parkinson's Disease Rating Scale-III score (MD=-0.61, 95% CI: [-4.10, 2.88], P=.73), Freezing of Gait Questionnaire score (MD=-0.83, 95% CI: [-2.98, 1.33], P=.45), or double support time (MD=-0.91, 95% CI: [-3.09, 1.26], P=.41). Evidence was evaluated as low quality. CONCLUSIONS: Wearable cueing devices may result in an immediate improvement on walking speed; however, there is no evidence that their use results in a significant improvement in other gait or motor functions.

A review of 2022 Chinese clinical guidelines on the management of hepatocellular carcinoma: updates and insights.

Significant improvements in the management of hepatocellular carcinoma (HCC) during the past three years have urged the timely update of clinical guidelines in China. In brief, aMAP score is newly recommended as an effective risk stratification tool to predict HCC occurrence especially for non-cirrhotic patients. Biomarker-based surveillance including 7 micro-RNA panel and GALAD score are advocated to assist early diagnosis. China liver cancer (CNLC) staging system proposed in the 2017 guideline continues to be the standard model for staging with modifications in the treatment allocations. Conversion therapies using multi-modal, high intensity strategies are advocated to facilitate subsequent resection for patients with technically unresectable CNLC stage Ia, Ib, IIa HCC, or technically resectable IIb, IIIa HCC. Super-selective transcatheter arterial chemoembolization (TACE) with the assistance of Cone-Beam CT if necessary is recommended to guarantee the efficacy of TACE. Hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin (FOLFOX) regimen alone or in combination with systemic therapy is recommended for TACE-refractory patients or for patients with locally advanced HCC. The systemic treatments for HCC have evolved considerably since atezolizumab plus bevacizumab, and suntilimab plus bevacizumab analogue showing superior survival benefit to sorafenib, and donafenib with comparable efficacy with sorafenib are added to the first-line treatments. In addition to regorafenib, apatinib, camrelizumab and tislelizumab are added as the second-line systemic therapies for patients who progressed on sorafenib. Updates in the 2022 Barcelona Clinic Liver Cancer (BCLC) guidelines and Japanese Society of Hepatology (JSH) consensus statement are also introduced and compared with the 2022 Chinese guidelines.

Apostasia Mitochondrial Genome Analysis and Monocot Mitochondria Phylogenomics.

Apostasia shenzhenica belongs to the subfamily Apostasioideae and is a primitive group located at the base of the Orchidaceae phylogenetic tree. However, the A. shenzhenica mitochondrial genome (mitogenome) is still unexplored, and the phylogenetic relationships between monocots mitogenomes remain unexplored. In this study, we discussed the genetic diversity of A. shenzhenica and the phylogenetic relationships within its monocotyledon mitogenome. We sequenced and assembled the complete mitogenome of A. shenzhenica, resulting in a circular mitochondrial draft of 672,872 bp, with an average read coverage of 122× and a GC content of 44.4%. A. shenzhenica mitogenome contained 36 protein-coding genes, 16 tRNAs, two rRNAs, and two copies of nad4L. Repeat sequence analysis revealed a large number of medium and small repeats, accounting for 1.28% of the mitogenome sequence. Selection pressure analysis indicated high mitogenome conservation in related species. RNA editing identified 416 sites in the protein-coding region. Furthermore, we found 44 chloroplast genomic DNA fragments that were transferred from the chloroplast to the mitogenome of A. shenzhenica, with five plastid-derived genes remaining intact in the mitogenome. Finally, the phylogenetic analysis of the mitogenomes from A. shenzhenica and 28 other monocots showed that the evolution and classification of most monocots were well determined. These findings enrich the genetic resources of orchids and provide valuable information on the taxonomic classification and molecular evolution of monocots.

Evaluation of novel anti-CEACAM6 antibody-based conjugates for radioimmunotheranostics of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant solid tumor that lacks early diagnostic methods. Recently, targeted immunotherapy and radiotherapy have been integrated with radionuclide-antibody conjugate drugs, which can be used for targeted diagnosis and dynamic imaging of tumors. CEACAM6 is overexpressed in pancreatic tumors and is a potential theranostic target for PDAC. We aimed to develop a novel targeted carrier for theranostics of PDAC and other solid tumors. METHODS: Based on camelid heavy-chain-only antibodies, we developed a CEACAM6-targeting recombinant antibody NY004, and evaluated it as a novel antibody-carrier for imaging and therapy of cancer in tumor models. We labeled NY004 with theranostic nuclides and applied this self-developed antibody platform in diagnostic imaging and antitumor assessment in PDAC models. RESULTS: Through microPET, IHC, and biodistribution assays, targeting and biodistribution of [89Zr]-NY004 in solid tumors including PDAC was examined, and the investigated tumors were all CEACAM6-positive malignancies. We found that NY004 was suitable for use as a drug carrier for radioimmunotheranostics. Our study showed that NY004 was characterized by high targeted uptake and a long retention time in PANC-1 tumors (up to 6 days post-injection), with good specificity and high imaging efficiency. Therapeutic evaluation of the radionuclide-labeled antibody drug [177Lu]-NY004 in PDAC tumor-bearing model revealed that NY004 had high and prolonged uptake in tumors, relatively low non-target organ uptake, and good anti-tumor efficacy. CONCLUSION: As a drug platform for radiotheranostics, CEACAM6-specific antibody NY004 met the requirements of easy-labeling, targeting specificity, and effective persistence in pancreatic adenocarcinoma tissues. KEY POINTS: • [89Zr]-NY004 has good specificity and high imaging efficiency, and is characterized by high tumor-targeting uptake and a long tumor retention time as a PET molecular imaging tracer. • Therapeutic radionuclide-conjugated antibody drug [177Lu]-NY004 has high uptake and prolonged uptake duration in tumors, low non-target organ uptake, and significant tumor-inhibiting efficacy in PDAC model. • The self-developed antibody structure NY004 is a promising drug platform for radioimmunotheranostics of CEACAM6-positive tumors including pancreatic ductal adenocarcinoma.

Pyroptosis, Metabolism, and Oxidation in Tumorigenesis: Mechanisms and Therapeutic Implications.

Significance: Pyroptosis is a discovered programmed cell death that is mainly executed by the gasdermin protein family. Cell swelling and membrane perforation are observed when pyroptosis occurs, and is accompanied by the liberation of cell contents. Recent Advances: As the study of pyroptosis continues to progress, there is increasing evidence that pyroptosis influences the development of tumors. In addition, the relationship between pyroptosis and tumor is diverse for different tissues and cells. Critical Issues: In this review, we first introduce the research history and molecular mechanisms of pyroptosis. Then we specifically discuss the link between pyroptosis and metabolic and oxidation in tumorigenesis. In the subsequent sections, we focus on the induction of pyroptosis in cancer and its potential role as a promising target for cancer therapy, and discuss the implications of pyroptosis in tumor treatment. In addition, we further summarize the therapeutic value of pyroptosis in tumor treatment. Future Directions: A detailed understanding of the role played by pyroptosis in tumors will help us to further explore tumor formation and progression and provide ideas for the development of new pyroptosis-based therapeutic approaches for patients. Antioxid. Redox Signal. 39, 512-530.

Targeting ferroptosis in cardio-metabolic-diseases: Mechanisms and therapeutic prospects.

Cardio-metabolic-diseases (cardio-metabolic-diseases) are leading causes of death and disability worldwide and impose a tremendous burden on whole society as well as individuals. As a new type of regulated cell death (RCD), ferroptosis is distinct from several classical types of RCDs such as apoptosis and necroptosis in cell morphology, biochemistry, and genetics. The main molecular mechanisms of ferroptosis involve iron metabolism dysregulation, mitochondrial malfunction, impaired antioxidant capacity, accumulation of lipid-related peroxides and membrane disruption. Within the past few years, mounting evidence has shown that ferroptosis contributes to the pathophysiological process in cardio-metabolic-diseases. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This review comprehensively summarizes the mechanism of ferroptosis in the development and progression of cardio-metabolic-diseases, so as to provide new insights for cardio-metabolic-diseases pathophysiology. Moreover, we highlight potential druggable molecules in ferroptosis signaling pathway, and discuss recent advances in management strategies by targeting ferroptosis for prevention and treatment of cardio-metabolic-diseases.

Seasonal variations, source apportionment and dry deposition of chemical species of total suspended particulate in Pengjia Yu Island, East China Sea.

Total of 172 total suspended particulate (TSP) samples and its chemical compositions were collected and analyzed from January to December 2010 in Pengjia Yu Island, an open region in East China Sea (ECS). Despite the predominance of sea-salt major ions (Na+, Cl-), the presence of non-sea-salt SO42- (nss-SO42-) and NO3- as well as combustion-derived trace metals clearly establishes the impact of anthropogenic sources over ECS. The annual contributions of coal, heavy-fuel oil and traffic to the measured chemical species were 21.0 %, 15.0 % and 15.5 %, respectively. Especially in spring, the contributions of crustal minerals to measured chemical species during dust period (33.6 %) were higher than that (13.2 %) during non-dust period. The calculated annual average dry deposition fluxes for trace metals and total inorganic nitrogen were 246.1 ± 345.8 µg/m2/d and 2950.4 ± 2245.0 µg/m2/d, suggesting that atmospheric deposition is an important source of nutrient elements for the south of ECS.

NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-ß/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer.

Pancreatic cancer (PaCa) is one of the most fatal malignancies of the digestive system, and most patients are diagnosed at advanced stages due to the lack of specific and effective tumor-related biomarkers for the early detection of PaCa. miR-492 has been found to be upregulated in PaCa tumor tissue and may serve as a potential therapeutic target. However, the molecular mechanisms by which miR-492 promotes PaCa tumor growth and progression are unclear. In this study, we first found that miR-492 in enhancer loci activated neighboring genes (NR2C1/NDUFA12/TMCC3) and promoted PaCa cell proliferation, migration, and invasion in vitro. We also observed that miR-492-activating genes significantly enriched the TGF-ß/Smad3 signaling pathway in PaCa to promote epithelial-mesenchymal transition (EMT) during tumorigenesis and development. Using CRISPR-Cas9 and ChIP assays, we further observed that miR-492 acted as an enhancer trigger, and that antagomiR-492 repressed PaCa tumorigenesis in vivo, decreased the expression levels of serum TGF-ß, and suppressed the EMT process by downregulating the expression of NR2C1. Our results demonstrate that miR-492, as an enhancer trigger, facilitates PaCa progression via the NR2C1-TGF-ß/Smad3 pathway.

Ferroptotic stress facilitates smooth muscle cell dedifferentiation in arterial remodelling by disrupting mitochondrial homeostasis.

Smooth muscle cell (SMC) phenotypic switch from a quiescent 'contractile' phenotype to a dedifferentiated and proliferative state underlies the development of cardiovascular diseases (CVDs); however, our understanding of the mechanism is still incomplete. In the present study, we explored the potential role of ferroptosis, a novel nonapoptotic form of cell death, in SMC phenotypic switch and related neointimal formation. We found that ferroptotic stress was triggered in cultured dedifferentiated SMCs and arterial neointimal tissue of wire-injured mice. Moreover, pro-ferroptosis stress was activated in arterial neointimal tissue of clinical patients who underwent carotid endarterectomy. Blockade of ferroptotic stress via administration of a pharmacological inhibitor or by global genetic overexpression of glutathione peroxidase-4 (GPX4), a well-established anti-ferroptosis molecule, delayed SMC phenotype switch and arterial remodelling. Conditional SMC-specific gene delivery of GPX4 using adreno-associated virus in the carotid artery inhibited ferroptosis and prevented neointimal formation. Conversely, ferroptosis stress directly triggered dedifferentiation of SMCs. Transcriptomics analysis demonstrated that inhibition of ferroptotic stress mainly targets the mitochondrial respiratory chain and oxidative phosphorylation. Mechanistically, ferroptosis inhibition corrected the disrupted mitochondrial homeostasis in dedifferentiated SMCs, including enhanced mitochondrial ROS production, dysregulated mitochondrial dynamics, and mitochondrial hyperpolarization, and ultimately inhibited SMC phenotypic switch and growth. Copper-diacetyl-bisN4-methylthiosemicarbazone (CuATSM), an agent used for clinical molecular imaging and that potently inhibits ferroptosis, prevented SMC phenotypic switch, neointimal formation and arterial inflammation in mice. These results indicate that pro-ferroptosis stress is likely to promote SMC phenotypic switch during neointimal formation and imply that inhibition of ferroptotic stress may be a promising translational approach to treat CVDs with SMC phenotype switch.

Tuning oxygen vacancy in Bi2WO6 by heteroatom doping for enhanced photooxidation-reduction properties.

Heteroatom doping was recently regarded as an effective method to tune the band gap and improve the separation and transfer of photogenerated electron-hole pairs in semiconductor photocatalysts. Herein, a novel S,F-codoped Bi2WO6 (S,F-Bi2WO6) with suitable oxygen vacancies was synthesized via the hydrothermal-calcination and post-sulfurization, for efficient Cr(VI) reduction and methyl orange (MO) degradation under visible light. The amount of surface oxygen vacancies could be controlled by adjusting the S/F ratio during the doping process, which modulated the band structure and photogenerated charge behavior of Bi2WO6. The optimal S0.10F-Bi2WO6 exhibited an excellent photooxidation-reduction performance, which Cr(VI) reduction and MO degradation efficiencies were 1.6 and 2.6 times than those of the pristine Bi2WO6 without oxygen vacancy under visible-light, respectively. The enhanced photooxidation-reduction performance was because the right amount of oxygen vacancies could effectively narrow the bandgap and improve the separation efficiency of electron-hole pairs. Thus, this work offered a mild and simply approach for preparing heteroatom doped Bi2WO6 and a potential to be extended to the synthesis of other doped materials for environmental remediation.

Ferroptosis inhibitor liproxstatin-1 alleviates metabolic dysfunction-associated fatty liver disease in mice: potential involvement of PANoptosis.

Ferroptosis is a new form of regulated cell death characterized by excessive iron accumulation and uncontrollable lipid peroxidation. The role of ferroptosis in metabolic dysfunction-associated fatty liver disease (MAFLD) is not fully elucidated. In this study we compared the therapeutic effects of ferroptosis inhibitor liproxstatin-1 (LPT1) and iron chelator deferiprone (DFP) in MAFLD mouse models. This model was established in mice by feeding a high-fat diet with 30% fructose in water (HFHF) for 16 weeks. The mice then received LPT1 (10 mg·kg-1·d-1, ip) or DFP (100 mg·kg-1·d-1, ig) for another 2 weeks. We showed that both LPT1 and DFP treatment blocked the ferroptosis markers ACSL4 and ALOX15 in MAFLD mice. Furthermore, LPT1 treatment significantly reduced the liver levels of triglycerides and cholesterol, lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), and ameliorated the expression of lipid synthesis/oxidation genes (Pparα, Scd1, Fasn, Hmgcr and Cpt1a), insulin resistance, mitochondrial ROS content and liver fibrosis. Importantly, LPT1 treatment potently inhibited hepatic apoptosis (Bax/Bcl-xL ratio and TUNEL+ cell number), pyroptosis (cleavages of Caspase-1 and GSDMD) and necroptosis (phosphorylation of MLKL). Moreover, LPT1 treatment markedly inhibited cleavages of PANoptosis-related caspase-8 and caspase-6 in MAFLD mouse liver. In an in vitro MAFLD model, treatment with LPT1 (100 nM) prevented cultured hepatocyte against cell death induced by pro-PANoptosis molecules (TNF-α, LPS and nigericin) upon lipid stress. On the contrary, DFP treatment only mildly attenuated hepatic inflammation but failed to alleviate lipid deposition, insulin resistance, apoptosis, pyroptosis and necroptosis in MAFLD mice. We conclude that ferroptosis inhibitor LPT1 protects against steatosis and steatohepatitis in MAFLD mice, which may involve regulation of PANoptosis, a coordinated cell death pathway that involves apoptosis, pyroptosis and necroptosis. These results suggest a potential link between ferroptosis and PANoptosis.

Identification of prognostic immune-related lncRNAs in pancreatic cancer.

Long noncoding RNAs (lncRNAs) play a critical role in the immune regulation and tumor microenvironment of pancreatic cancer (PaCa). To construct a novel immune-related prognostic risk model for PaCa and evaluate the prognostic prediction of lncRNAs, essential immune-related lncRNAs (IRlncRNAs) were identified by Pearson correlation analysis of differentially expressed immune-related genes (IRGs) and IRlncRNAs in PaCa from The Cancer Genome Atlas (TCGA) and GTEx databases. Least absolute shrinkage and selection operator (LASSO) regression was also applied to construct a prognostic risk model of IRlncRNAs, and gene set enrichment analysis (GSEA) was further applied for functional annotation for these IRlncRNAs. A total of 148 IRlncRNAs were identified in PaCa to construct a prognostic risk model. Among them, lncRNA LINC02325, FNDC1-AS1, and ZEB2-AS1 were significantly upregulated in 69 pairs of PaCa tissues by qRT-PCR. ROC analyses showed that LINC02325 (AUC = 0.80), FNDC1-AS1 (AUC = 0.76), and ZEB2-AS1 (AUC = 0.75) had a good predictive effect on 5-year survival prognosis. We demonstrated that high expression levels of ZEB2-AS1 and LINC02325 were not only positively associated with tumor size and CA199, but elevated levels of ZEB2-AS1 and FNDC1-AS1 were also positively correlated with tumor stage. GSEA further revealed that immune-related pathways were mainly enriched in the high-risk groups. Several immune-related algorithms demonstrated that four IRlncRNAs were related to immune infiltration, immune checkpoints, and immune-related functions. Thus, the prognostic risk model based on IRlncRNAs in Paca indicates that the four IRlncRNA signatures may serve as predictors of survival and potential predictive biomarkers of the pancreatic tumor immune response.

Comparison of specimen quality among the standard suction, slow-pull, and wet suction techniques for EUS-FNA: A multicenter, prospective, randomized controlled trial.

Background and Objectives: Standard suction technique (SST), slow-pull technique (SPT), and wet suction technique (WEST) of EUS-FNA are designed to improve the diagnostic yields of solid and solid-cystic lesions. We conducted a multicenter, prospective, randomized crossover trial to compare SST, SPT, and WEST on specimen quality and diagnostic accuracy using a 22G needle. Methods: Patients with solid or solid-cystic lesions referred for EUS-FNA at four tertiary hospitals from December 2017 to August 2019 were considered eligible. All lesions were sampled using a 22G needle by the three techniques performed consecutively in a randomized order. The primary outcome was quality of the specimen acquired by each technique regarding blood contamination, tissue integrity and cellularity for diagnosis, graded on a predefined scale. The secondary outcomes were the diagnostic yield of EUS-FNA and the incidence of adverse events. ClinicalTrial. gov registration number: NCT03567863. Results: A total of 300 patients (mean age, 60.6 years, 188 men) were enrolled. WEST was superior (mean score 4.02 ± 1.51) over SST (3.67 ± 1.57, P = 0.018), but comparable to SPT (3.83 ± 1.55, P = 0.370) in overall specimen quality evaluation. WEST produced better tissue integrity (1.42 ± 0.74) and higher cellularity (1.32 ± 0.80) than SST and SPT. SPT (1.43 ± 0.69) was superior to SST (1.27 ± 0.72, P = 0.004) and WEST (1.28 ± 0.71, P = 0.006) in avoiding blood contamination. WEST achieved a diagnostic accuracy of 74.7%, higher than SST (64.4%, P = 0.007) and SPT (65.0%, P = 0.012). One bleeding event occurred with a pancreatic lesion. Conclusions: WEST was comparable to SPT and superior to SST in the overall quality of the specimen and achieved highest diagnostic yield.

Cerebrospinal Fluid sTREM2 in Alzheimer's Disease Is Associated with Both Amyloid and Tau Pathologies but not with Cognitive Status.

BACKGROUND: Cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is considered a biomarker of microglial activation. The relationships between CSF sTREM2 levels and Alzheimer's disease (AD) CSF core biomarkers, cognitive status, and neurodegeneration remain unclear. OBJECTIVE: To assess the association between CSF sTREM2 levels and AD progression and other AD hallmarks. METHODS: Using the Alzheimer's Disease Neuroimaging Initiative database, we investigated 1,035 participants, including 310 cognitively normal controls, 527 patients with mild cognitive impairment, and 198 patients with dementia. They were grouped according to CSF pathology (A/T profile) severity. CSF sTREM2 levels were compared between the groups, and linear regression analysis was performed to evaluate the factors affecting sTREM2 levels. The predictive effectiveness of sTREM2 levels was tested, and the correlation with other indicators was explored. The increase rate was assessed using linear mixed-effects models. RESULTS: Higher CSF sTREM2 levels were associated with older age as well as higher CSF p-tau or t-tau and amyloid-ß levels (all p < 0.001), but not with cognitive status. sTREM2 levels were not correlated with the baseline or longitudinal scale and neuroimaging result changes, and could not predict clinical conversion, but were correlated with multiple non-amyloid-ß and non-tau CSF cytokines related to inflammation and neurodegeneration (p < 0.0001). The increased sTREM2 expression rate did not change among groups. CONCLUSION: CSF sTREM2 levels were jointly determined by age, amyloid-ß, and tau pathologies, leading to complex AD cognitive continuum changes. Although sTREM2 levels could not predict cognitive deterioration and neurodegeneration, they could reflect the microglial state as a non-specific biomarker.

Segmentation Method of Cerebral Aneurysms Based on Entropy Selection Strategy.

The segmentation of cerebral aneurysms is a challenging task because of their similar imaging features to blood vessels and the great imbalance between the foreground and background. However, the existing 2D segmentation methods do not make full use of 3D information and ignore the influence of global features. In this study, we propose an automatic solution for the segmentation of cerebral aneurysms. The proposed method relies on the 2D U-Net as the backbone and adds a Transformer block to capture remote information. Additionally, through the new entropy selection strategy, the network pays more attention to the indistinguishable blood vessels and aneurysms, so as to reduce the influence of class imbalance. In order to introduce global features, three continuous patches are taken as inputs, and a segmentation map corresponding to the central patch is generated. In the inference phase, using the proposed recombination strategy, the segmentation map was generated, and we verified the proposed method on the CADA dataset. We achieved a Dice coefficient (DSC) of 0.944, an IOU score of 0.941, recall of 0.946, an F2 score of 0.942, a mAP of 0.896 and a Hausdorff distance of 3.12 mm.