Investigating the causal relationship of gut microbiota with GERD and BE: a bidirectional mendelian randomization.

BACKGROUND: Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett's esophagus(BE) hasn't been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis. METHODS: Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE. RESULTS: 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01-1.17) and BE(OR = 1.388, 95%CI = 1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways. CONCLUSIONS: This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.

Comprehensive Analysis of Immune Signatures in Primary Biliary Cholangitis and Autoimmune Hepatitis.

Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) are autoimmune diseases that target hepatocytes and bile duct cells, respectively. Despite their shared autoimmune nature, the differences in immunologic characteristics between them remain largely unexplored. This study seeks to elucidate the unique immunological profiles of PBC and AIH, and to identify key differences. We comprehensively analyzed various T-cell subsets and their receptor expression in a cohort of 45 patients, including 27 PBC and 18 AIH cases. Both diseases exhibited T cell exhaustion and senescence along with a surge in inflammatory cytokines. Significantly increased CD38+HLA-DR+CD8+T cell populations were observed in both diseases. AIH was characterized by an upregulation of CD8+TEMRA, CD4+TEM, and CD4+TEMRA cells, and a concurrent reduction in Treg cells. In contrast, PBC displayed a pronounced presence of Tfh cells and a contraction of CD4-CD8-T cell populations. Correlation analysis revealed that NKP46+NK frequency was closely tied to ALT and AST levels, and TIGIT expression on T cells was associated with GLB level in AIH. In PBC, there is a significant correlation between Tfh cells and ALP levels. Moreover, the identified immune landscapes in both diseases strongly related to disease severity. Through logistic regression analysis, γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies emerged as distinct markers capable of differentiating PBC from AIH. In conclusion, our analyses reveal that PBC and AIH share similarities and differences regarding to immune profiles. And γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies are potential noninvasive immunological markers that can differentiate PBC from AIH.

Efficacy and safety of self-made covered coronary stent in the treatment of coronary artery perforation.

OBJECTIVE: To observe the efficacy and safety of self-made covered coronary stent in the treatment of coronary artery perforation. METHODS: Covered coronary stent was prepared by wrapping 3 M film on the surface of coronary stents. The beagle dogs were divided into control group and experimental group. A drug-eluting stent (DES) was implanted in the control group. The covered stent was applied to block the coronary branches of beagle dogs. The CaIMR value after stent placement was calculated by FlashAngio software. The effect of blocking the coronary branches on blood flow was observed by coronary angiography (CAG). The condition of the implanted stent was observed by optical coherence tomography (OCT), and the histopathologic examination of the coronary vessel implanted stent was performed by HE staining. RESULTS: The best number of layers was 2. Compared with the control group, the CaIMR of the experimental group increased (p < 0.05). A lot of in-stent thrombosis were found in the experimental group and obvious blood flow obstruction during follow-up. HE staining showed that stents implanted in the two groups adhered well to the wall of the blood vessel, but in-stent thrombosis and intimal hyperplasia were founded in the experimental group, while the in-stent restenosis was not founded. CONCLUSION: The self-made coronary covered stent can effectively block the leakage caused by coronary perforation, but the stent endothelialization is poor, which easily causes stent thrombosis and restenosis, so it is not recommended as a routine remedy.

Immune-Ageing Evaluation of Peripheral T and NK Lymphocyte Subsets in Chinese Healthy Adults.

Ageing is often accompanied with a decline in immune system function, resulting in immune ageing. Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence. The change in immune phenotype is a key indication of the diseased or healthy status. However, the changes in lymphocyte number and phenotype brought about by ageing have not been comprehensively analysed. Here, we analysed T and natural killer (NK) cell subsets, the phenotype and cell differentiation states in 43,096 healthy individuals, aged 20-88 years, without known diseases. Thirty-six immune parameters were analysed and the reference ranges of these subsets were established in different age groups divided into 5-year intervals. The data were subjected to random forest machine learning for immune-ageing modelling and confirmed using the neural network analysis. Our initial analysis and machine modelling prediction showed that naïve T cells decreased with ageing, whereas central memory T cells (Tcm) and effector memory T cells (Tem) increased cluster of differentiation (CD) 28-associated T cells. This is the largest study to investigate the correlation between age and immune cell function in a Chinese population, and provides insightful differences, suggesting that healthy adults might be considerably influenced by age and sex. The age of a person's immune system might be different from their chronological age. Our immune-ageing modelling study is one of the largest studies to provide insights into 'immune-age' rather than 'biological-age'. Through machine learning, we identified immune factors influencing the most through ageing and built a model for immune-ageing prediction. Our research not only reveals the impact of age on immune parameter differences within the Chinese population, but also provides new insights for monitoring and preventing some diseases in clinical practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00106-0.

Studying the imaging features and infarction mechanism of vertebrobasilar dolichoectasia with high-resolution magnetic resonance imaging.

The mechanisms underlying ischemic infarction in patients with vertebrobasilar dolichoectasia (VBD) remain unclear. In this study, we retrospectively analyzed the imaging characteristics of high-resolution magnetic resonance imaging (HR-MRI) in patients with VBD to explore the possible mechanisms of ischemic stroke (IS) in patients with VBD. Patients with VBD were recruited from the HR-MRI database between July 2017 and June 2021. HR-MRI was used to evaluate the diameter, bifurcation height, laterality, arterial dissection, and atherosclerotic plaques of the basilar artery (BA). Transcranial Doppler was used to measure the vertebrobasilar mean velocity (Vm), peak systolic velocity (Vs), end-diastolic velocity (Vd), and pulsatile index. Twenty-six patients with VBD were enrolled, of which 15 had IS and 11 did not. The incidence of classical vascular risk factors, including age, sex, hypertension, diabetes, and hypercholesterolemia, did not differ significantly between the two groups. The BA diameters of the stroke group were significantly higher than that of the nonstroke group (6.57 ± 1.00 mm vs. 5.06 ± 0.50 mm, p = 0.000). The height of the BA bifurcation in the stroke and nonstroke groups was statistically significant (p = 0.002). Compared with the nonstroke group, the Vm, Vs, and Vd of the BA in the stroke group were lower, but the difference was not significant. In the 16 patients with atherosclerotic stenosis, 30 atherosclerotic plaques were found in the BA, 18 (60%) in the greater curvature, and 12 (40%) in the lesser curvature. In addition, one artery dissection (on the lesser curvature) and two dissecting aneurysms (on the greater curvature) were found in the BA of three patients, respectively. The BA diameter and bifurcation height are factors related to IS in patients with VBD. The mechanism of stroke in patients with VBD may involve abnormal hemodynamics, artery dissection, and atherosclerosis. HR-MRI is a useful method for evaluating the risk and underlying mechanism of stroke in patients with VBD.

Block Matching Pyramid Algorithm-Based Analysis on Efficacy of Shexiang Baoxin Pills Guided by Echocardiogram (ECG) on Patients with Angina Pectoris in Coronary Heart Disease.

This paper was aimed to explore the application of the block matching pyramid (BMP) algorithm in echocardiographic spot tracking in patients with coronary heart disease (CHD) and angina pectoris, as well as the effect of Shexiang Baoxin pills (a kind of drug containing musk, which is good for cardiac diseases) on blood lipids, cardiac function, and curative effect. 206 patients with CHD angina pectoris in the hospital from July 2018 to May 2020 were selected as the research subjects and were enrolled into the control (Ctrl) group (conventional treatment, n = 103) and the observation group (the Shexiang Baoxin pill was given on the basis of conventional treatment, n = 103) in random. Then, the patients' echocardiograms were obtained, and the BMP algorithm was used to track the echocardiograms. At 12 months after treatment, the total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were compared. Besides, the differences between left ventricular end-systolic volume (LVESV), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic dimension (LVEDD), cardiac index (CI), cardiac output (CO), and LVEF were observed. Finally, the efficacy of angina pectoris and electrocardiogram was calculated. It was found that the BMP algorithm can track the echocardiograms and display the movement and displacement of the patients' left ventricle. After treatment, in contrast with the Ctrl, the levels of TC, TG, and LDL-C in the observation group were obviously lower (P < 0.05); the LVESV, LVEDV, and LVEF were obviously lower (P < 0.05), the LVESD, LVEDD, CO, and CI were obviously higher (P < 0.05), the total score of angina after treatment was obviously lower (P < 0.05), and the total effective rates of angina pectoris and echocardiogram were obviously higher (P < 0.05). In conclusion, echocardiographic spot tracking can realize the diagnosis of patients with CHD angina pectoris, and Shexiang Baoxin pill can regulate the blood lipid level and improve the echocardiographic indicators and the clinical efficacy is obvious.

40 kHz, 20 ns acousto-optically Q-switched 4 µm Fe:ZnSe laser pumped by a fluoride fiber laser.

An actively Q-switched mid-infrared Fe:ZnSe laser pumped by a continuous wave fluoride fiber laser has been developed. Stable operation with a pulse duration of 20 ns and a repetition rate of 40 kHz at 4 µm was achieved. The maximum peak power was 1.1 kW. The high-repetition rate, high-peak power nanosecond pulsed laser, which has been created for the first time, to the best of our knowledge, in an actively Q-switched Fe:ZnSe laser, should prove a suitable light source for laser processing and molecular sensing.

Development of the ABEEMσπ Polarization Force Field for Base Pairs with Amino Acid Residue Complexes.

DNA damage caused by oxidized bases can lead to aging and cancer in living beings. Luckily, a repair enzyme is able to repair the oxidized bases. The key step is to accurately recognize the oxidized bases, which mainly rely on complex hydrogen bond interactions. We have calibrated the charge parameters and torsional parameters of the ABEEMσπ polarization force field (ABEEMσπ PFF) to accurately describe the intermolecular and intramolecular interactions. Taking the experiment and quantum chemical method as the benchmark, a series of properties of base pair-amino acid residue systems, DNA and DNA-protein interaction systems were calculated and compared with those of other force fields. We have done a tremendous amount of tasks in testing, calibrations, and analyses. The ABEEMσπ PFF not only explicitly gives the position and the partial charge of lone-pair electrons but also introduces a function kHB to fit special electrostatic interactions in hydrogen bond interaction regions. Therefore, it can accurately simulate the polarization effect and charge transfer of hydrogen bond interactions, especially for charged systems and sulfur-containing systems, such as the binding energy between amino acid and base pairs (24-28 kcal/mol), which is induced by charge transfer. The RMSD of ABEEMσπ PFF is 1.18 kcal/mol, whereas the RMSD of Amber OL15 is 8.21 kcal/mol. The relative positions of the amino acid residue have significantly changed, and the hydrogen bonds were broken when simulated by fixed charge force fields. In addition, owing to refitting the reasonable torsional parameters, the geometric structures optimized by ABEEMσπ PFF were well consistent with those of the M06-2X/6-311++G** method, but the simulations by fixed force fields have a large rotation of methyl and distortion of the plane of the base pair. After extensive MD simulation with four test DNAs and a DNA-protein system, we conclude that ABEEMσπ PFF shows better agreement when compared to experimental structures, which illustrates the reliability of our model and the transferability of the parameters.