Integration of microbiomics, metabolomics, and transcriptomics reveals the therapeutic mechanism underlying Fuzheng-Qushi decoction for the treatment of lipopolysaccharide-induced lung injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng-Qushi decoction (FZQS) is a practical Chinese herbal formula for relieving cough and fever. Therefore, the action and specific molecular mechanism of FZQS in the treatment of lung injury with cough and fever as the main symptoms need to be further investigated. AIMS OF THE STUDY: To elucidate the protective effects of FZQS against lung injury in mice and reveal its potential targets and key biological pathways for the treatment of lung injury based on transcriptomics, microbiomics, and untargeted metabolomics analyses. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was used to induce a mouse model of lung injury, followed by the administration of FZQS. ELISA was used to detect IL-1ß, IL-6, IL-17A, IL-4, IL-10, and TNF-α, in mouse lung tissues. Macrophage polarization and neutrophil activation were measured by flow cytometry. RNA sequencing (RNA-seq) was applied to screen for differentially expressed genes (DEGs) in lung tissues. RT-qPCR and Western blot assays were utilized to validate key DEGs and target proteins in lung tissues. 16S rRNA sequencing was employed to characterize the gut microbiota of mice. Metabolites in the gut were analyzed using untargeted metabolomics. RESULTS: FZQS treatment significantly ameliorated lung histopathological damage, decreased pro-inflammatory cytokine levels, and increased anti-inflammatory cytokine levels. M1 macrophage levels in the peripheral blood decreased, M2 macrophage levels increased, and activated neutrophils were inhibited in mice with LPS-induced lung injury. Importantly, transcriptomic analysis showed that FZQS downregulated macrophage and neutrophil activation and migration and adhesion pathways by reversing 51 DEGs, which was further confirmed by RT-qPCR and Western blot analysis. In addition, FZQS modulated the dysbiosis of the gut microbiota by reversing the abundance of Corynebacterium, Facklamia, Staphylococcus, Paenalcaligenes, Lachnoclostridium, norank_f_Muribaculaceae, and unclassified_f_Lachnospiraceae. Meanwhile, metabolomics analysis revealed that FZQS significantly regulated tryptophan metabolism by reducing the levels of 3-Indoleacetonitrile and 5-Hydroxykynurenine. CONCLUSION: FZQS effectively ameliorated LPS-induced lung injury by inhibiting the activation, migration, and adhesion of macrophages and neutrophils and modulating gut microbiota and its metabolites.

68 Ga-FAPI-RGD PET/CT Detected Skull Metastasis Better Than 18 F-FDG in a Patient With Radioiodine-Refractory Differentiated Thyroid Cancer.

ABSTRACT: A 60-year-old woman underwent resection of a right humeral tumor 1 year ago, and postoperative pathology indicated metastatic papillary thyroid cancer. She had her first 131 I treatment after a total thyroidectomy. Subsequent whole-body imaging after 131 I administration revealed 131 I-avid metastases in the left parietal bone. These metastases were observed to be larger during her second 131 I treatment, conducted 6 months later. Consequently, the patient was diagnosed with radioiodine-refractory differentiated thyroid cancer. 68 Ga-FAPI-RGD PET/CT demonstrated higher tracer uptake and clearer lesion boundaries compared with 18 F-FDG PET/CT. This suggests that 177 Lu-FAPI-RGD could potentially serve as a treatment option for radioiodine-refractory differentiated thyroid cancer.

Enzymatic Acylation of Black Rice Anthocyanins and Evaluation of Antioxidant Capacity and Stability of Their Derivatives.

In this study, the structure of the anthocyanin fractions isolated from black rice (Oryza sativa L.) was modified by the enzyme catalysis method using caffeic acid as an acyl donor. At the same time, the effects of the acylation on the lipophilicity, antioxidant activity, and stability of black rice anthocyanins were comprehensively evaluated. The structural analyses of acylated derivatives based on ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, ultra-high-performance liquid chromatography-high-resolution mass spectrometry, and thermogravimetric analysis revealed that caffeic acid was efficiently grafted onto the anthocyanins of black rice through an acylated reaction, while the acylation binding site was on glucoside. When the mass ratios of anthocyanins to caffeic acid were 1:1, the A319/AVis-max value of acylated anthocyanins reached 6.37. Meanwhile, the lipophilicity of acylated derivatives was enhanced. The antioxidant capacity (DPPH and FRAP) and stability (thermal, pH, and light stability) were significantly increased. Overall, the study results provide deeper insights into controlling anthocyanin homeostasis in food processing, broadening the application of colored grain products.

Identifying potential biomarkers of idiopathic pulmonary fibrosis through machine learning analysis.

Idiopathic pulmonary fibrosis (IPF) is the most common and serious type of idiopathic interstitial pneumonia, characterized by chronic, progressive, and low survival rates, while unknown disease etiology. Until recently, patients with idiopathic pulmonary fibrosis have a poor prognosis, high mortality, and limited treatment options, due to the lack of effective early diagnostic and prognostic tools. Therefore, we aimed to identify biomarkers for idiopathic pulmonary fibrosis based on multiple machine-learning approaches and to evaluate the role of immune infiltration in the disease. The gene expression profile and its corresponding clinical data of idiopathic pulmonary fibrosis patients were downloaded from Gene Expression Omnibus (GEO) database. Next, the differentially expressed genes (DEGs) with the threshold of FDR < 0.05 and |log2 foldchange (FC)| > 0.585 were analyzed via R package "DESeq2" and GO enrichment and KEGG pathways were run in R software. Then, least absolute shrinkage and selection operator (LASSO) logistic regression, support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF) algorithms were combined to screen the key potential biomarkers of idiopathic pulmonary fibrosis. The diagnostic performance of these biomarkers was evaluated through receiver operating characteristic (ROC) curves. Moreover, the CIBERSORT algorithm was employed to assess the infiltration of immune cells and the relationship between the infiltrating immune cells and the biomarkers. Finally, we sought to understand the potential pathogenic role of the biomarker (SLAIN1) in idiopathic pulmonary fibrosis using a mouse model and cellular model. A total of 3658 differentially expressed genes of idiopathic pulmonary fibrosis were identified, including 2359 upregulated genes and 1299 downregulated genes. FHL2, HPCAL1, RNF182, and SLAIN1 were identified as biomarkers of idiopathic pulmonary fibrosis using LASSO logistic regression, RF, and SVM-RFE algorithms. The ROC curves confirmed the predictive accuracy of these biomarkers both in the training set and test set. Immune cell infiltration analysis suggested that patients with idiopathic pulmonary fibrosis had a higher level of B cells memory, Plasma cells, T cells CD8, T cells follicular helper, T cells regulatory (Tregs), Macrophages M0, and Mast cells resting compared with the control group. Correlation analysis demonstrated that FHL2 was significantly associated with the infiltrating immune cells. qPCR and western blotting analysis suggested that SLAIN1 might be a signature for the diagnosis of idiopathic pulmonary fibrosis. In this study, we identified four potential biomarkers (FHL2, HPCAL1, RNF182, and SLAIN1) and evaluated the potential pathogenic role of SLAIN1 in idiopathic pulmonary fibrosis. These findings may have great significance in guiding the understanding of disease mechanisms and potential therapeutic targets in idiopathic pulmonary fibrosis.

Primary Pancreatic Lymphoma Masquerading as Carcinoma on 18 F-FDG PET/CT.

ABSTRACT: A 76-year-old man with yellowish discoloration of sclera and skin for 2 months was referred to 18 F-FDG PET/CT for metabolic characterization of the mass in the pancreas. The images showed intense FDG uptake in the head of the pancreas, as well as a lymph nodal mass in the hepatic hilar region, which was consistent with pancreatic malignancy. Histopathologic findings showed characteristic findings of diffuse large B-cell lymphoma with no evidence of adenocarcinoma.

Multiform-based Baduanjin exercise prevention and treatment for idiopathic pulmonary fibrosis: study protocol for a randomized controlled trial.

INTRODUCTION: In this study, we will combine the traditional Baduanjin with Yijin Jing and Wuqinxi to create an optimized Baduanjin exercise program with three different forms (vertical, sitting, and horizontal) to adapt to idiopathic pulmonary fibrosis (IPF) patients in vairous stages of the disease. The purpose of this study is to explore and compare the therapeutic effects of this multi-form Baduanjin, traditional Baduanjin, and resistance training on lung function and limb motor function in IPF patients. The goal of this study is to prove a novel optimal exercise prescription strategy of Baduanjin exercise for improving and protecting lung function in IPF patients. METHODS/DESIGN: A single-blind and randomized controlled trial is used to conduct this study, while the randomization list will be generated using a computerized random number generator and opaque sealed envelopes with group allocation will be prepared. It will be strictly followed to blind the outcome assessors. and until the experiment's conclusion, participants won't know which group they are enrolled in. Patients between the ages of 35 and 80 who have stable diseases and have not regularly practiced Baduanjin exercise in the past will be included. They are divvied up into the following five groups at random: (1) The conventional care group (control group, CG), (2) The traditional Baduanjin exercise group (TG), (3) The modified Baduanjin exercise group (IG), (4) The resistance exercise group (RG) (5) The modified Baduanjin exercise combined with resistance exercise group (IRG). Those CG participants only received the usual treatment, while TC, IG, and RG participants exercised 1 h twice a day for 3 months. MRG participants will have a 3-month intervention with 1 h of Modified Baduanjin Exercise and 1 H of Resistance Training for each day. Every week, all groups underwent will supervis one-day training, with the exception of the control group. The Pulmonary Function Testing (PFT), HRCT, and 6MWT are the main outcome variables. The St. George Respiratory Questionnaire and mMRC are used as secondary outcome measures. DISCUSSION: This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. Because it consists of three forms, including vertical, sitting, and horizontal, it is more adaptable to the various disease stages and actual situations of IPF patients and may compensate for the shortcomings of conventional pulmonary rehabilitation and traditional Baduanjin. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055559 . Registered on 12 January 2022.

Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia.

Deficit schizophrenia (DS) patient is a homogenous subtype of schizophrenia that includes primary and enduring negative symptoms. This study aimed to compare the differences in cognitive functioning and plasma levels of C-reactive protein (CRP) and inflammatory cytokines among DS patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). A total of 141 schizophrenia patients and 67 HCs were included in this study. The schizophrenia patients were divided into DS (N= 51) and NDS (N=90) groups based on the Proxy for the Deficit Syndrome Scale (PDS). The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the clinical symptoms and cognitive performances, respectively. The plasma level of CRP, IL-1ß, Il-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ were measured using enzyme-linked immunosorbent assays (ELISAs). Our results showed that DS patients had the worst cognitive performance, especially in the immediate memory, attention, and language dimensions, compared to the NDS and HC groups. Compared to the HCs group, DS patients had higher levels of CRP, IL-1ß, IL-6, IL-8, IFN-γ, and total proinflammatory cytokines, and NDS patients had higher levels of IL-1ß, IFN-γ, and proinflammatory cytokines. We also found that CRP levels were significantly increased in DS patients compared to NDS patients. Moreover, stepwise logistic regression analysis revealed that CRP is an independent risk factor for DS. Sex stratification analysis showed significant differences in almost all cytokines in female samples but not in male samples. The significant differences in cognitive performance and inflammatory components among groups suggest that deficit syndrome is an independent endophenotype of schizophrenia patients with unique immune-inflammatory features, but may have sex characteristics.

Association Between SIRT1, Cytokines, and Metabolic Syndrome in Schizophrenia Patients With Olanzapine or Clozapine Monotherapy.

Objective: Previous studies consistently showed the interaction between Sirtuin 1 (SIRT1) and immune inflammation is significantly related to metabolic abnormalities, but their role in the pathogenesis of metabolic syndrome caused by second-generation antipsychotics (SGAs) in schizophrenia patients largely remains unknown. Hence, the present study aimed to fill this gap. Methods: A total of 54 schizophrenia patients with olanzapine or clozapine monotherapy [metabolic syndrome (MetS)/non-MetS patients, 27/27] and 67 healthy subjects were recruited in the present study. The Positive and Negative Syndrome Scale was used, and the plasma levels of SIRT1, interleukin 6 (IL-6), IL-8, IL-10, and tumor necrosis factor α (TNF-α) were measured. Results: The results showed that schizophrenia patients treated with olanzapine or clozapine (both MetS and non-MetS groups) had significantly higher plasma levels of IL-6, IL-10, and TNF-α compared to normal controls (all P < 0.05). Moreover, the MetS patients exhibited markedly lower plasma levels of SIRT1 and higher plasma levels of IL-6 than non-MetS patients and normal controls (all P < 0.05). However, there were no significant differences in IL-8 levels between groups. Our correlation analysis showed that SIRT1 was significantly correlated with diastolic blood pressure, triglyceride, and high-density lipoprotein cholesterol in schizophrenia patients. The stepwise logistic regression analysis further identified the IL-6 × SIRT1 (ß = -0.463, t = 10.040, P = 0.002) as the influencing factor for the MetS in the patients. Conclusion: Our preliminary findings suggest that SIRT1 interacted with inflammatory cytokines associated with MetS in schizophrenia patients treated with SGA monotherapy.