Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors.

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

Long-term survival outcomes of endoscopic therapy vs. surgical resection in patients with cardia gastrointestinal stromal tumor.

The ideal surgical approach for treating cardia gastrointestinal stromal tumor (GIST) is not clearly established. This study aimed to assess the long-term survival results among patients who received endoscopic therapy (ET) or surgical resection (SR) for cardia GIST. Cardia GIST patients from 2000 to 2019 were selected from the surveillance, epidemiology, and end result (SEER) database. Multiple imputation (MI) was applied to handle missing data, and propensity score matching (PSM) was carried out to mitigate selection bias during comparisons. Demographic and clinical characteristics' effects on overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier analyses and multivariate Cox proportional hazard models. A total of 330 patients with cardia GIST were enrolled, including 47 (14.2%) patients with ET and 283 (85.8%) patients with SR. The 5-year OS and CSS rates in the ET and SR groups were comparable [before PSM, (OS) (76.1% vs. 81.2%, P = 0.722), (CSS) (95.0% vs. 89.3%, P = 0.186); after PSM, (OS) (75.4% vs. 85.4%, P = 0.540), (CSS) (94.9% vs. 92.0%, P = 0.099)]. Moreover, there was no significant difference between ET and SR in terms of long-term OS (hazard ratio [HR] 0.735, 95% confidence interval [CI] 0.422-1.282) and CSS (HR 1.560, 95% CI 0.543-4.481). Our study found no significant disparity in long-term survival outcomes between ET and SR in cardia GIST patients, implying that ET could be a valid surgical strategy for treating cardia GIST.

Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study.

Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.

Transcutaneous Electrical Acupoint Stimulation Combined with Moderate Sedation of Remimazolam Tosilate in Gastrointestinal Endoscopy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. METHODS: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. RESULTS: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. CONCLUSIONS: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. TRIAL REGISTRATION: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

Ultrawide Spectra Camouflage Coatings from Metallic Flake Powder.

Ultrawide-spectra-compatible camouflage materials are imperative for military science and national security due to the continuous advancement of various sophisticated multispectral detectors. However, ultrawide spectra camouflage still has challenges, as the spectral requirements for different bands are disparate and even conflicting. This work demonstrates an ultrawide spectra camouflage material compatible with visible (VIS, 400-800 nm), infrared (IR, 3-5 and 8-14 µm), and microwave (S-Ku bands, 2-12 GHz). The carbon nanotubes adsorbed on porous anodic alumina/aluminum flake powder (CNTs@PAA/AFP) material for ultrawide spectra camouflage is composed of bioinspired porous alumina surface layers for low visible reflection and aluminum flake powder substrate for low infrared emissivity, while the surface of the porous alumina layers is loaded with carbon nanotubes for microwave absorption. Compared with previous low-emissivity materials, CNTs@PAA/AFP has omnidirectional low reflectance (Ravg = 0.29) and high gray scale (72%) in the visible band. Further, it exhibits low emissivity (ε3-5µm = 0.15 and ε8-14µm = 0.18) in the dual infrared atmospheric window, which reduces the infrared lock-on range by 59.6%/49.8% in the mid/far-infrared band at high temperatures (573 K). The infrared camouflage performance calculated from the radiation temperature of CNTs@PAA/AFP coatings is enhanced to over 65%, which is at least 4 times greater than that of its substrate. In addition, the CNTs@PAA/AFP coating achieves high microwave absorption (RLmin = -42.46 dB) and an effective absorption bandwidth (EAB = 7.43 GHz) in the microwave band (S-Ku bands) due to the enhancement of interfacial polarization and conductive losses. This study may introduce new insight and feasible methods for multispectral manipulation, electromagnetic signal processing, and thermal management via bioinspired structural design and fabrication.

Identification and Visualization of Polystyrene Microplastics/Nanoplastics in Flavored Yogurt by Raman Imaging.

The contamination of food by microplastics has garnered widespread attention, particularly concerning the health risks associated with small-sized microplastics. However, detecting these smaller microplastics in food poses challenges attributed to the complexity of food matrices and instrumental and method limitations. Here, we employed Raman imaging for visualization and identification of polystyrene particles synthesized in polymerization reactions, ranging from 400 to 2600 nm. We successfully developed a quantitative model of particle size and concentration for polystyrene, exhibiting excellent fit (R2 of 0.9946). We established procedures for spiked flavored yogurt using synthesized polystyrene, providing fresh insights into microplastic extraction efficiency. Recovery rates calculated from models validated the method's feasibility. In practical applications, the assessment of the size, type, shape, and quantity of microplastics in unspiked flavored yogurt was conducted. The most common polymers found were polystyrene, polypropylene, and polyethylene, with the smallest polystyrene sizes ranging from 1 to 10 µm. Additionally, we conducted exposure assessments of microplastics in branded flavored yogurt. This study established a foundation for developing a universal method to quantify microplastics in food, covering synthesis of standards, method development, validation, and application.

Discovery and genetic characterization of novel paramyxoviruses from small mammals in Hubei Province, Central China.

Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.

Effectiveness and safety of thoracic manipulation in the treatment of neck pain: An updated systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to evaluate the effectiveness and safety of thoracic manipulation (TM) in patients with neck pain (NP). OBJECTIVE: The purpose of this meta-analysis was to evaluate the effectiveness and safety of thoracic manipulation (TM) in patients with neck pain (NP). METHODS: Seven electronic databases were searched from their inception through October 2023 by two authors. The methodological quality assessments were performed with the Physiotherapy Evidence Database (PEDro) scale. Pain, cervical range of motion (ROM), disability, and quality of life (QOL) were estimated for TM treatment in patients with NP. RESULTS: Eighteen randomized controlled trials (RCTs) with 914 patients were included with a PEDro score of 6.923 ± 3.120. Pooled effect sizes of pain (SMD =-0.481, 95% CI -0.653 to -0.309, P= 0.000), disability (SMD =-1.435, 95% CI -2.480 to -0.390, P= 0.007), QOL-physical component score (PCS) (SMD = 0.658, 95% CI 0.290 to 1.025, P= 0.000), ROM of flexion (SMD = 0.921, 95% CI 0.287 to 1.555, P= 0.000), ROM of extension (SMD = 0.572, 95% CI 0.321 to 0.822, P= 0.000), ROM of left lateral flexion (SMD = 0.593, 95% CI 0.075 to 1.112, P= 0.025) and ROM of left rotation (SMD = 0.230, 95% CI 0.010 to 0.450, P= 0.04) were favored by the TM group. CONCLUSIONS: TM provides short-term effect on relieving neck pain, increasing cervical ROM, and disability in patients with NP without serious side effects. Continuous therapy and distraction therapy are recommended as optimal choice on reducing pain and improving cervical ROM, especially in patients with chronic NP (> 3 months). The TM-induced improvements in the QOL of patients with NP should be verified by more further high-quality RCTs.

[Methods for research on structures and functions of traditional Chinese medicine proteins].

Traditional Chinese medicine proteins(TCMPs) not only have nutritional values and biological activities but also serve as key enzymes in the synthesis of pharmacodynamic components in traditional Chinese medicines. They play a role in the synthesis of pharmacodynamic components by regulating biosynthesis and selective synthesis pathways and controlling drug quality and stability. The recent years have witnessed great progress in the research on the structures and functions of proteins using various methods and technologies. However, the research on the structures and functions of TCMPs lags behind. Therefore, it is urgent to study the structures and functions of TCMPs using modern means to promote the discovery of innovative drugs based on TCMPs and clarify the synthesis pathways of pharmacodynamic components. This study introduces the latest techniques for studying protein structures and functions, including spectroscopy, mass spectrometry, nuclear magnetic resonance, X-ray crystal diffraction, microscopy, and structure prediction. Furthermore, this paper introduces the methods for protein functional studies, including liquid chromatography-mass spectrometry, co-immunoprecipitation, yeast two-hybrid, and pull-down assay. By systematically reviewing these techniques and methods, this paper provides technical references for the structural identification and functional studies of TCMPs, with the aim of promoting the in-depth exploration of the structures and functions of TCMPs.

SIRT3 regulates cardiolipin biosynthesis in pressure overload-induced cardiac remodeling by PPARγ-mediated mechanism.

Cardiac remodeling is the primary pathological feature of chronic heart failure (HF). Exploring the characteristics of cardiac remodeling in the very early stages of HF and identifying targets for intervention are essential for discovering novel mechanisms and therapeutic strategies. Silent mating type information regulation 2 homolog 3 (SIRT3), as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolism. However, whether SIRT3 plays a role in cardiac remodeling by regulating the biosynthesis of mitochondrial cardiolipin (CL) is unknown. In this study, we induced pressure overload in wild-type (WT) and SIRT3 knockout (SIRT3-/-) mice via transverse aortic constriction (TAC). Compared with WT mouse hearts, the hearts of SIRT3-/- mice exhibited more-pronounced cardiac remodeling and fibrosis, greater reactive oxygen species (ROS) production, decreased mitochondrial-membrane potential (ΔΨm), and abnormal mitochondrial morphology after TAC. Furthermore, SIRT3 deletion aggravated TAC-induced decrease in total CL content, which might be associated with the downregulation of the CL synthesis related enzymes cardiolipin synthase 1 (CRLS1) and phospholipid-lysophospholipid transacylase (TAFAZZIN). In our in vitro experiments, SIRT3 overexpression prevented angiotensin II (AngII)- induced aberrant mitochondrial function, CL biosynthesis disorder, and peroxisome proliferator-activated receptor gamma (PPARγ) downregulation in cardiomyocytes; meanwhile, SIRT3 knockdown exacerbated these effects. Moreover, the addition of GW9662, a PPARγ antagonist, partially counteracted the beneficial effects of SIRT3 overexpression. In conclusion, SIRT3 regulated PPARγ-mediated CL biosynthesis, maintained the structure and function of mitochondria, and thereby protected the myocardium against cardiac remodeling.

Cotransport of nanoplastics and plastic additive bisphenol AF (BPAF) in unsaturated hyporheic zone: Coupling effects of surface functionalization and protein corona.

The ecological risk of combined pollution from microplastics (MPs) and associated contaminants usually depends on their interactions and environmental behavior, which was also disturbed by varying surface modifications of MPs. In this study, the significance of surface functionalization and protein-corona on the cotransport of nanoplastics (NPs; 100 nm) and the related additive bisphenol AF (BPAF) was examined in simulated unsaturated hyporheic zone (quartz sand; 250-425 µm). The electronegative bovine serum albumin (BSA) and electropositive trypsin were chosen as representative proteins, while pristine (PNPs), amino-modified (ANPs), and carboxyl-modified NPs (CNPs) were representative NPs with different charges. The presence of BPAF inhibited the mobility of PNPs/CNPs, but enhanced the release of ANPs in hyporheic zone, which was mainly related to their hydrophobicity changes and electrostatic interactions. Meanwhile, the NPs with high mobility and strong affinity to BPAF became effective carriers, promoting the cotransport of BPAF by 16.4 %-26.4 %. The formation of protein-coronas altered the mobility of NPs alone and their cotransport with BPAF, exhibiting a coupling effect with functional groups. BSA-corona promoted the transport of PNPs/CNPs, but this promoting effect was weakened by the presence of BPAF via increasing particle aggregation and hydrophobicity. Inversely, trypsin-corona aggravated the deposition of PNPs/CNPs, but competition deposition sites and increased energy barrier caused by coexisting BPAF reversed this effect, facilitating the cotransport of trypsin-PNPs/CNPs in hyporheic zone. However, BPAF and protein-coronas synergistically promoted the mobility of ANPs, owing to competition deposition sites and decreased electrostatic attraction. Although all of the NPs with two protein-coronas reduced dissolved BPAF in the effluents via providing deposition sites, the cotransport of total BPAF was improved by the NPs with high mobility (BSA-PNPs/CNPs) or high affinity to BPAF (BSA/trypsin-ANPs). However, the trypsin-PNPs/CNPs inhibited the transport of BPAF due to their weak mobility and adsorption with BPAF. The results provide new insights into the role of varying surface modifications on NPs in the vertical cotransport of NPs and associated contaminants in unsaturated hyporheic zone.

Multicomponent nickel-molybdenum-tungsten-based nanorods for stable and efficient alkaline seawater splitting.

The electrolysis of seawater for hydrogen production holds promise as a sustainable technology for energy generation. Developing water-splitting catalysts with low overpotential and stable operation in seawater is essential. In this study, we employed a hydrothermal method to synthesize NiMoWOX microrods (NiMoWOX@NF). Subsequently, an annealing process yielded a composite N-doped carbon-coated Ni3N/MoO2/WO2 nanorods (NC@Ni3N/MoO2/WO2@NF), preserving the ultrahigh-specific surface area of the original structure. A two-electrode electrolytic cell was assembled using NC@Ni3N/MoO2/WO2@NF as the cathode and NiMoWOX@NF as the anode, demonstrating exceptional performance in seawater splitting. The cell operated at a voltage of 1.51 V with a current density of 100 mA·cm-2 in an alkaline seawater solution. Furthermore, the NC@Ni3N/MoO2/WO2@NF || NiMoWOX@NF electrolytic cell exhibited remarkable stability, running continuously for over 120 h at a current of 1100 mA·cm-2 without any observable delay. These experimental results are corroborated by density functional theory calculations. The NC@Ni3N/MoO2/WO2@NF || NiMoWOX@NF electrolyzer emerges as a promising option for industrial-scale hydrogen production through seawater electrolysis.

JUNO high purity nitrogen plant.

The Jiangmen Underground Neutrino Observatory (JUNO) is a 20 kt low level radioactivity liquid scintillator detector in a laboratory 650 m underground. An excellent energy resolution and a large volume offer exciting opportunities for addressing many important topics in neutrino physics. High purity nitrogen is an important factor to ensure the low background of the JUNO detector. High Purity Nitrogen (HPN) is used for detector purging, pipe cleaning, and scintillator purification, among other things in JUNO. According to JUNO's requirements, the radon concentration in HPN should be less than 10 µBq/m3. To meet this requirement, A high-purity nitrogen plant with 100 Nm3/h maximum rate was designed and constructed. Low-temperature adsorption technology is used to remove radioactive impurities in nitrogen. High purification efficiency was ensured by using an activated carbon column with high column height-to-diameter ratio. Electrostatic collection and low-temperature enrichment methods are combined to measure radon in nitrogen. After ten days of continuous operation at 50 Nm3/h flux rate, the plant can to reduce the radon concentration in nitrogen from 37.4±1.8µBq/m3 to less than 1.33 µBq/m3. After HPN with flow rate of 50 Nm3/h passing through low-background pipeline (About 1.3 km), the radon concentration of HPN is 5.6±0.6µBq/m3.

Strategies to Guide Preemptive Waitlisting and Equity in Waittime Accrual by Race/Ethnicity.

BACKGROUND: Use of eGFR to determine preemptive waitlisting eligibility may contribute to racial/ethnic disparities in access to waitlisting, which can only occur when the eGFR falls to ≤20 ml/min per 1.73 m 2 . Use of an alternative risk-based strategy for waitlisting may reduce these inequities ( e.g. , a kidney failure risk equation [KFRE] estimated 2-year risk of kidney failure) rather than the standard eGFR threshold for determining waitlist eligibility. Our objective was to model the amount of preemptive waittime that could be accrued by race and ethnicity, applying two different strategies to determine waitlist eligibility. METHODS: Using electronic health record data, linear mixed models were used to compare racial/ethnic differences in preemptive waittime that could be accrued using two strategies: estimating the time between an eGFR ≤20 and 5 ml/min per 1.73 m 2 versus time between a 25% 2-year predicted risk of kidney failure (using the KFRE, which incorporates age, sex, albuminuria, and eGFR to provide kidney failure risk estimation) and eGFR of 5 ml/min per 1.73 m 2 . RESULTS: Among 1290 adults with CKD stages 4-5, using the Chronic Kidney Disease Epidemiology Collaboration equation yielded shorter preemptive waittime between an eGFR of 20 and 5 ml/min per 1.73 m 2 in Black (-6.8 months; 95% confidence interval [CI], -11.7 to -1.9), Hispanic (-10.2 months; -15.3 to -5.1), and Asian/Pacific Islander (-10.3 months; 95% CI, -15.3 to -5.4) patients compared with non-Hispanic White patients. Use of a KFRE threshold to determine waittime yielded smaller differences by race and ethnicity than observed when using a single eGFR threshold, with shorter time still noted for Black (-2.5 months; 95% CI, -7.8 to 2.7), Hispanic (-4.8 months; 95% CI, -10.3 to 0.6), and Asian/Pacific Islander (-5.4 months; -10.7 to -0.1) individuals compared with non-Hispanic White individuals, but findings only met statistical significance criteria in Asian/Pacific Islander individuals. When we compared potential waittime availability using a KFRE versus eGFR threshold, use of the KFRE yielded more equity in waittime for Black ( P = 0.02), Hispanic ( P = 0.002), and Asian/Pacific Islander ( P = 0.002) patients. CONCLUSIONS: Use of a risk-based strategy was associated with greater racial equity in waittime accrual compared with use of a standard single eGFR threshold to determine eligibility for preemptive waitlisting.

Nanocarriers for gene delivery to the cardiovascular system.

Cardiovascular diseases have posed a great threat to human health. Fortunately, gene therapy holds great promise in the fight against cardiovascular disease (CVD). In gene therapy, it is necessary to select the appropriate carriers to deliver the genes to the target cells of the target organs. There are usually two types of carriers, viral carriers and non-viral carriers. However, problems such as high immunogenicity, inflammatory response, and limited loading capacity have arisen with the use of viral carriers. Therefore, scholars turned their attention to non-viral carriers. Among them, nanocarriers are highly valued because of their easy modification, targeting, and low toxicity. Despite the many successes of gene therapy in the treatment of human diseases, it is worth noting that there are still many problems to be solved in the field of gene therapy for the treatment of cardiovascular diseases. In this review, we give a brief introduction to the common nanocarriers and several common cardiovascular diseases (arteriosclerosis, myocardial infarction, myocardial hypertrophy). On this basis, the application of gene delivery nanocarriers in the treatment of these diseases is introduced in detail.

Diagnostic role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in abdominal lymphadenopathy of unknown etiology.

Background: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an established method for the evaluation of abdominal organ lesions. However, there are few studies on EUS-FNA for abdominal lymph node (LN) lesions. The purpose of this study was to evaluate the diagnostic role of EUS-FNA in isolated abdominal lymphadenopathy (LAP). Methods: A retrospective analysis was performed on patients with isolated abdominal LAP who underwent a EUS-FNA examination. The diagnosis was made based on cytology, histology, and immunohistochemical (IHC) studies. The area under curve (AUC) value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Results: A total of 99 patients were included in this study. The final diagnoses were metastatic tumor (n = 32), lymphoma (n = 32), tuberculosis (n = 17), sarcoidosis (n = 5), castleman's disease (n = 1), and reactive LAP (n = 12). The AUC value, sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNA in the diagnosis of malignant LAP were 0.9531, 90.6, 100, 100, 85.4, and 93.9%, respectively. For the diagnosis of lymphoma, the accuracy of EUS-FNA combined with IHC staining was 94.9%. Retroperitoneal LN enlargement is more commonly associated with lymphoma, while hepatic hilar LN enlargement predominantly suggests benign conditions or metastatic tumors. Malignant lymph nodes are more likely to be regular border, circular/quasi-circular, and fusion. Lymphomas are more likely to present with fusion and heterogeneous echogenicity than metastatic tumors. Conclusion: EUS-FNA is a safe and effective method to diagnose isolated abdominal LAP.

Disulfiram relieves severe acute pancreatitis by inhibiting GSDMD-dependent NETs formation.

OBJECTIVES: Severe acute pancreatitis (SAP) is characterized by pancreatic and systemic inflammation and persistent organ failure. Neutrophil extracellular traps (NETs) are considered to play an important role in the development of SAP. We aimed to explore the effect of disulfiram (DSL), a newly developed anti-inflammatory drug, on NETs in SAP. METHODS: A mouse model of SAP was induced by caerulein and lipopolysaccharide, and the mice were divided into the normal control group, the DSL group, the SAP group, and the SAP treated with 50 mg/kg (50DSLSAP) and 100 mg/kg DSL (100DSLSAP) groups, respectively. The severity of SAP was evaluated based on the morphological and biochemical changes. Gasdermin D (GSDMD) expression was evaluated in vivo and in vitro to verify the effect of DSL. Additionally, the expressions of NETs were also evaluated in vivo and in vitro in SAP with and without DSL treatment to explore the possible mechanism of DSL on SAP. RESULTS: Pancreatic inflammatory injury increased in the SAP group, which was alleviated by DSL. GSDMD, a protein related to the formation of NETs, increased in SAP. Expressions of NETs were also promoted in the in vivo SAP model and by phorbol myristate acetate (PMA) in vitro. Moreover, DSL inhibited the expressions of GSDMD and NETs in vivo. The results were further confirmed in the in vitro experiment. CONCLUSIONS: NETs are highly associated with inflammatory injury in SAP. DSL inhibits NETs formation by downregulating GSDMD, which in turn relieves the inflammation of SAP. Our study may provide a possible therapeutic target for SAP.