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Background and Objectives: A majority of pancreatic malignancies are unresectable at the time of presentation and require EUS-guided fine-needle aspiration or fine-needle biopsy (EUS-FNA/FNB) for diagnosis. With the advent of precision therapy, there is an increasing need to use EUS-FNA/FNB sample for genetic analysis. Next-generation sequencing (NGS) is a preferred technology to detect genetic mutations with high sensitivity in small specimens. We performed a meta-analysis to evaluate the adequacy of EUS-FNA/FNB for NGS in pancreatic malignancies., Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from database inception to November 11, 2023. The primary outcome was the proportion of sufficient sample acquired by EUS-FNA/FNB in pancreatic malignancies for NGS. Secondary outcomes were the proportion of sufficient sample for NGS in pancreatic ductal adenocarcinoma (PDAC) and the detection rates of mutations in KRAS, TP53, CDKN2A, and SMAD4 and actionable mutations in PDAC. The pooled proportions were calculated using a random-effects model. Potential sources of heterogeneity were investigated with subgroup analyses and meta-regression., Results: Twenty studies with 881 samples were included. The pooled adequacy of EUS-FNA/FNB sample for NGS was 89.9% (95% CI, 80.8%-96.7%) in pancreatic malignancies and 92.0% (95% CI, 81.3%-98.8%) in PDAC. Screening sample suitability before NGS testing was associated with lower adequacy in subgroup analysis (79.7% vs. 98.4%, P = 0.001). The pooled prevalences of mutations in KRAS, TP53, CDKN2A, and SMAD4 in PDAC were 87.4% (95% CI, 83.2%-91.2%), 62.6% (95% CI, 53.2%-71.7%), 20.6% (95% CI, 11.9%-30.8%), and 19.4% (95% CI, 11.2%-29.1%), respectively. The pooled prevalence of potentially actionable mutations in PDAC was 14.5% (95% CI, 8.2%-22.0%)., Conclusions: In the majority of cases, EUS-FNA/FNB can acquire adequate sample for NGS and identify tumor-specific mutations in patients with pancreatic malignancies. Strict pre-analysis screening criteria may negatively impact the sample adequacy and the success rate for NGS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Scholar Media Publishing.)

Background: A number of recent observational studies have indicated a correlation between the constitution of gut microbiota and the incidence of pancreatitis. Notwithstanding, observational studies are unreliable for inferring causality because of their susceptibility to confounding, bias, and reverse causality, the causal relationship between specific gut microbiota and pancreatitis is still unclear. Therefore, our study aimed to investigate the causal relationship between gut microbiota and four types of pancreatitis., Methods: An investigative undertaking encompassing a genome-wide association study (GWAS) comprising 18,340 participants was undertaken with the aim of discerning genetic instrumental variables that exhibit associations with gut microbiota, The aggregated statistical data pertaining to acute pancreatitis (AP), alcohol-induced AP (AAP), chronic pancreatitis (CP), and alcohol-induced CP (ACP) were acquired from the FinnGen Consortium. The two-sample bidirectional Mendelian randomization (MR) approach was utilized. Utilizing the Inverse-Variance Weighted (IVW) technique as the cornerstone of our primary analysis. The Bonferroni analysis was used to correct for multiple testing, In addition, a number of sensitivity analysis methodologies, comprising the MR-Egger intercept test, the Cochran's Q test, MR polymorphism residual and outlier (MR-PRESSO) test, and the leave-one-out test, were performed to evaluate the robustness of our findings., Results: A total of 28 intestinal microflora were ascertained to exhibit significant associations with diverse outcomes of pancreatitis. Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288-2.519, p = 0.008) has a strong causality with ACP after the Bonferroni-corrected test, in order to assess potential reverse causation effects, we used four types of pancreatitis as the exposure variable and scrutinized its impact on gut microbiota as the outcome variable, this analysis revealed associations between pancreatitis and 30 distinct types of gut microflora. The implementation of Cochran's Q test revealed a lack of substantial heterogeneity among the various single nucleotide polymorphisms (SNP)., Conclusion: Our first systematic Mendelian randomization analysis provides evidence that multiple gut microbiota taxa may be causally associated with four types of pancreatitis disease. This discovery may contribute significant biomarkers conducive to the preliminary, non-invasive identification of Pancreatitis. Additionally, it could present viable targets for potential therapeutic interventions in the disease's treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Qin, Ran, Pan, Hong, Wang, Zhang, Shen, Liu, Lu, Chen, Bai, Zhang, Zhou and Zou.)

Purpose: The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism., Methods: The potential mechanism of ZQGCD's therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software., Results: Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream., Conclusion: The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Huang et al.)

Introduction: Multidomain intervention approaches have emerged as a potential strategy to reduce dementia risk. We sought to describe the baseline assessment approaches, health conditions, and risk profiles for brain aging of participants in the randomized controlled Multimodal INterventions to delay Dementia and disability in rural China (MIND-China)., Methods: MIND-China engaged residents who were ≥60 years of age and living in rural communities in the western Shandong province. In March to September 2018, all participants underwent the core module assessments via face-to-face interviews, clinical examinations, neuropsychological testings, and laboratory tests. Specific modules of examination were performed for sub-samples, including brain magnetic resonance imaging scans, genetic and blood biochemical markers, actigraphy testing, cardiopulmonary coupling analysis for sleep quality and disturbances, audiometric testing, and optical coherence tomography examination. We performed descriptive analysis., Results: In total, 5765 participants (74.9% of all eligible residents) undertook the baseline assessments. The mean age was 70.9 years (standard deviation, 5.9), 57.2% were women, 40.6% were illiterate, and 88.3% were farmers. The overall prevalence of common chronic diseases was 67.2% for hypertension, 23.4% for dyslipidemia, 23.5% for heart disease, 14.4% for diabetes mellitus, and 5.4% for dementia. The prevalence rates of hypertension, diabetes mellitus, dyslipidemia, obesity, heart disease, depressive symptoms, and dementia were higher in women than in men ( P  < .05). Overall, 87.1% of the participants had at least two of the 15 chronic diseases (89.3% in women vs 84.2% in men, P  < .001). Participants examined for the specific modules were younger, more likely to be women, and more educated than those not examined., Discussion: Comprehensive baseline assessments of participants in MIND-China provide extremely valuable data sources for interdisciplinary research into the complex relationships of aging, health, brain aging, and functional consequences among older adults living in the rural communities., Highlights: MIND-China is a multimodal intervention study among rural residents ≥60 years of age.At baseline, 5765 participants undertook the interdisciplinary assessments.The baseline assessments consisted of core module and specific modules.Specific modules included brain magnetic resonance imaging (MRI), blood biomarkers, ActiGraph, cardiopulmonary coupling (CPC), pure-tone audiometry (PTA), and optical coherence tomography (OCT)., Competing Interests: Miia Kivipelto received honoraria for lectures from Biogen, Nutricia, Nestlé, and Roche. Miia Kivipelto is on the advisory boards of Combinostics, the Swedish Care International, Roche, and Biogen. Miia Kivipelto is the Chair of the Committee for Clinical Therapy Research at the Swedish Research Council, and ADDF Board of Governors; the WHO Guidelines Development Group; Committee Member of the Global Council on Brain Health; and the Scientific Lead of World‐Wide FINGERS Network. Maria Carrillo is in the Advisory Board of US POINTER STUDY. Maria Carrillo and Heather Snyder are full‐time employee of the Alzheimer's Association. All other authors have no conflict of interest to declare., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Brillouin-based LiDAR is an alternative remote sensing technique for measuring the distribution profiles of temperature, salinity, and sound speed in the upper ocean mixed layer. Its principle is based on the dependence of Brillouin frequency shift on the temperature, salinity, and depth of ocean. Therefore, it is necessary to investigate the effect of various seawater parameters on Brillouin frequency shift for ocean remote sensing by using the Brillouin LiDAR. Here we theoretically and experimentally investigate the influence of temperature, salinity, and pressure (depth) of seawater on Brillouin frequency shift in the upper ocean for the first time. Numerical simulations of the distribution profiles of temperature, salinity, and Brillouin frequency shift in the upper-ocean mixed layers of East China Sea and South China Sea were performed, respectively, by employing the Brillouin equations and the World Ocean Atlas 2018 (WOA18). A special ocean simulation system was designed to carry out the stimulated Brillouin scattering (SBS) experiments for validating the numerical simulations. The results show that the seawater temperature is the most important factor for the Brillouin frequency shift in the upper-ocean mixed layer compared with the salinity and pressure. At the same salinity and pressure, the frequency shift increases by more than 10 MHz for every 1 °C increase in temperature. Also, the differences of Brillouin frequency shift between experimental and theoretical values at the same parameter conditions were analyzed. The experimental results coincide well with the theoretical simulations. This work is essential to future applications of Brillouin LiDAR in remote sensing of the temperature, salinity, or sound velocity profiles of ocean.

In this paper, we present a novel approach for studying Boolean function in a graph-theoretic perspective. In particular, we first transform a Boolean function f of n variables into an induced subgraph H f of the n -dimensional hypercube, and then, we show the properties of linearly separable Boolean functions on the basis of the analysis of the structure of H f . We define a new class of graphs, called hyperstar, and prove that the induced subgraph H f of any linearly separable Boolean function f is a hyperstar. The proposal of hyperstar helps us uncover a number of fundamental properties of linearly separable Boolean functions in this paper.