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In this paper, we report an elderly patient who had been experiencing poor appetite for one month and yellowing of the skin and sclera for two months before visiting the Department of Geriatrics at Peking Union Medical College Hospital. The patient's blood tests revealed significantly elevated levels of serum total bilirubin, direct bilirubin, and blood sugar. The serum IgG4 level nearly tripled. Abdominal imaging examinations revealed diffuse pancreatic lesions, narrowing of the intrapancreatic segment of the common bile duct, and thickening and marked enhancement of the common hepatic duct, left and right hepatic ducts, and branches. Blood glucose was also significantly elevated during the course of the disease. Moreover, nutritional assessment found that the patient was malnourished. After multidisciplinary discussion, a medium dose of oral methylprednisolone was prescribed to the patient due to his advanced age and multiple chronic conditions. The dose was then quickly reduced while the patient simultaneously received low-dose mycophenolate mofetil (MMF) treatment. As a result, the patient's bilirubin level significantly decreased, jaundice subsided, and his body weight returned to normal with improved physical function. Throughout the diagnosis and treatment process, a multidisciplinary team actively participated in discussions and gradually identified the underlying cause. This exemplifies the crucial role of interdisciplinary collaboration in effectively diagnosing and treating complex illnesses in elderly patients.

The gut microbiota and their metabolites play a critical role in the maintenance of host immune homeostasis. The dysbiosis and gut microbiota-derived metabolites are closely associated with the initiation and development of multiple autoimmune diseases. Among the microbiota metabolites, short-chain fatty acids, tryptophan and its derivatives, and bile acids are the most widely studied. In this review, the metabolic pathway of the microbiota metabolites, their functions in the immune response and the current findings on their correlation with autoimmune diseases are summarized, with the hope of revealing the role of gut microbiota-derived metabolites on the pathogenesis of autoimmune diseases.

Primary Sjögren's syndrome (pSS) is a prevalent autoimmune disorder wherein CD4+ T cells play a pivotal role in its pathogenesis. However, the underlying mechanisms driving the hyperactivity of CD4+ T cells in pSS remain poorly understood. This study aimed to investigate the potential role of immunometabolic alterations in driving the hyperactivity of CD4+ T cells in pSS. We employed Seahorse XF assay to evaluate the metabolic phenotype of CD4+ T cells, conducted flow cytometry to assess the effector function and differentiation of CD4+ T cells and measured the level of intracellular reactive oxygen species (ROS). Additionally, transcriptome sequencing, PCR, and Western blotting were utilized to examine the expression of glycolytic genes. Our investigation revealed that activated CD4+ T cells from pSS patients exhibited elevated aerobic glycolysis, rather than oxidative phosphorylation, resulting in excessive production of IFN-γ and IL-17A. Inhibition of glycolysis by 2-Deoxy-D-glucose reduced the expression of IFN-γ and IL-17A in activated CD4+ T cells and mitigated the differentiation of Th1 and Th17 cells. Furthermore, the expression of glycolytic genes, including CD3E, CD28, PIK3CA, AKT1, mTOR, MYC, LDHA, PFKL, PFKFB3, and PFKFB4, was upregulated in activated CD4+ T cells from pSS patients. Specifically, the expression and activity of LDHA were enhanced, contributing to an increased level of intracellular ROS. Targeting LDHA with FX-11 or inhibiting ROS with N-acetyl-cysteine had a similar effect on reversing the dysfunction of activated CD4+ T cells from pSS patients. Our study unveils heightened aerobic glycolysis in activated CD4+ T cells from pSS patients, and inhibition of glycolysis or its metabolite normalizes the dysfunction of activated CD4+ T cells. These findings suggest that aerobic glycolysis may be a promising therapeutic target for the treatment of pSS. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and closely associated with the immune system. Emerging evidence suggests that blood immune cell phenotypes in patients with LUAD may undergo alterations. Nevertheless, the limited amount of relevant research makes it difficult to understand the causal links between LUAD and changes in the immune cells. This study aimed to reveal the potential causal relationships between 731 immune cell phenotypes and LUAD. Methods: A bidirectional two‐sample Mendelian randomization (MR) analysis was used to clarify causal relationships. Four types of immune phenotypes, absolute cell counts, relative cell counts, median fluorescence intensities (MFIs) of surface antigens, and morphological parameters, were investigated in this study. Heterogeneity tests, horizontal pleiotropy tests, and leave‐one‐out analyses were performed to validate the reliability of our study. Results: A total of 26 immune cell characteristics were identified as contributing to the occurrence of LUAD. Memory B cells, IgD−CD38br cells, CD4+ regulatory T cells (Tregs), and plasmacytoid dendritic cells (DCs) may play a role in the development of LUAD. Through reverse MR, our study discovered that the presence of LUAD also induced changes in the expression levels of 16 immune cell traits involving specific surface markers and various types of immune cells, some of which pertain to antigen presentation and immune activation processes. Conclusion: Our study demonstrated causal links between several immune cell phenotypes and LUAD, thereby providing indications of the potentially oncogenic physiological state and early screening biomarkers for future research. [ABSTRACT FROM AUTHOR]

Background: The identification of biomarkers predicting the treatment response of rheumatoid arthritis (RA) is important. [68 Ga]Ga-FAPI-04 showed markedly increased uptake in the joints of patients with RA. The purpose of this study is to investigate whether [68 Ga]Ga-FAPI-04 PET/CT can be a predictor of treatment response in RA. Results: Nineteen patients diagnosed with RA in the prospective cohort study were finally enrolled. Both total synovitis uptake (TSU) and metabolic synovitis volume (MSV) in [68 Ga]Ga-FAPI-04 and [18F]FDG PET/CT of the responders were significantly higher than those in non-responders according to Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) response criteria at 3-months' follow-up (P < 0.05). The PET joint count (PJC) detected in [68 Ga]Ga-FAPI-04 and [18F]FDG PET/CT were also significantly higher in CDAI responders than non-responders (P = 0.016 and 0.045, respectively). The clinical characteristics of disease activity at baseline did not show significant difference between the responders and non-responders, except CRP (P = 0.035 and 0.033 in CDAI and SDAI response criteria, respectively). The baseline PJCFAPI, TSUFAPI and MSVFAPI > cutoff values in [68 Ga]Ga-FAPI-04 PET/CT successfully discriminated CDAI and SDAI responders and non-responders at 3-months' follow-up. Conclusion: [68 Ga]Ga-FAPI-04 uptake at baseline were significantly higher in early responders than those in non-responders. Trial registration ClinicalTrials. NCT04514614. Registered 13 August 2020, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000A4PN&selectaction=Edit&uid=U0001JRW&ts=2&cx=-x9t7cp [ABSTRACT FROM AUTHOR]

Summary: Different raw rice and starters will affect the quality of Chinese rice wine (CRW). This study focused on the quality (flavour components, total phenolic content and antioxidant capacity) between Hong Qu japonica rice wine and Wheat Qu glutinous rice wine. Free amino acids and volatile compounds were analysed respectively. Total phenolic content was compared using Folin–Ciocalteu methods and antioxidant activity using DPPH, ABTS+ and FRAP methods. The results indicated that total free amino acid content of CRW ranged from 0.959 ± 0.09 to 3.229 ± 0.24 g L−1. About 65 volatile compounds were obtained in wine samples, mainly including alcohols, esters, aldehydes, acids, phenols and ethers. Isopentanol, isobutanol, phenylethyl alcohol, ethyl lactate, diethyl succinate, benzaldehyde, furfural and 2,4‐ditert‐butylphenol were the prominent aroma components in samples. Total phenolic content in samples ranged from 0.27 ± 0.00 to 0.45 ± 0.01 mg GAE mL−1. Experimental samples showed different radical scavenging capacity and ferric‐reducing capacity. These results proved that japonica rice wine with Hong Qu had abundant flavour components and strongest antioxidant capacity, the brewing raw material can be better developed in the production of CRW. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by B cell hyperactivation and hypergrammaglobulinemia. Currently, the role of metabolic pathways in the B cells of pSS patients is poorly defined. Here, we showed that upon cytosine phosphate‐guanine (CpG)/sCD40L/IL‐4 stimulation, B cells proportionally increased glycolysis and oxygen consumption, and compared with B cells from healthy controls (HCs), B cells from pSS patients exhibited higher glycolysis capacity and maximal oxidative respiration (OXPHOS). We also found that glucose transporter 1 (GLUT1) expression in B cells from pSS patients was significantly higher than that in B cells from HCs. Treatment with 2‐deoxy‐d‐glucose (2‐DG) inhibited the activation of B cells in pSS patients. Both 2‐DG and Metformin inhibited the proliferation, formation of plasma/plasmablasts and decreased the IgG and IgM levels in the supernatants of B cells from pSS patients. Furthermore, inhibition of mTORC1 by rapamycin had an effect similar to that of 2‐DG, suppressing B cell activation, proliferation and antibody production. Taken together, we demonstrated that B cells from pSS patients are more metabolically active than those from HCs and suggested that the mTORC1‐GLUT1 glycolysis pathways were the major drivers of B cell hyperactivation and autoantibody production in pSS patients. [ABSTRACT FROM AUTHOR]

Objectives To explore the survival and risk factors for cancer occurrence after SLE (SLE-CA). Methods Patients with cancer diagnosed after SLE in Peking Union Medical College Hospital between January 2006 and September 2017 were recruited and followed. Data regarding medication-related and disease-related factors and survival were collected and compared with matched controls. Logistic regressions were applied to identify risk factors. The Kaplan–Meier method with a log-rank test was performed to evaluate survival. Results Forty-five SLE-CA patients and 128 controls were included, with the most common cancer site being the female genital system. SLE-CA patients were exposed to a higher cumulative dosage of CYC, with less mucocutaneous and haematologic involvement and higher anti-dsDNA positivity. At the time of cancer diagnosis, SLE-CA patients had lower SLEDAI 2000 (SLEDAI-2K), tended to achieve Definitions of Remission in SLE remission and minimal disease activity, but had higher SLICC/ACR Damage Index. Multivariable analysis identified high dosage of CYC [odds ratio (OR) 1.027, 95% CI 1.008, 1.046; P  = 0.005] and low SLEDAI-2K at cancer diagnosis (OR 0.756, 95% CI 0.579, 0.986; P  = 0.039) as risk factors. Mucocutaneous (OR 0.330, 95% CI 0.110, 0.991; P  = 0.048) and haematologic involvement (OR 0.304, 95% CI 0.103, 0.902; P  = 0.032) were negatively associated with cancer occurrence after SLE. The 5- and 10-year survival rates in SLE-CA patients were 95.2% and 92.1%, respectively. No significant difference of survival was observed between SLE-CA patients and controls (P  = 0.177). Conclusion High dosage of CYC and disease-related factors (low SLEDAI-2K, less mucocutaneous and haematologic involvement) were related factors for cancer occurrence after SLE, while no survival difference was observed. [ABSTRACT FROM AUTHOR]