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Background Cardiopulmonary exercise testing (CPET) is essential for assessing the maximal exercise capacity of patients with chronic obstructive pulmonary disease (COPD) and for developing rehabilitation prescriptions. Body composition has been shown to be associated with CPET results, which is complex, time-consuming, contraindicated, and risky, and cannot be performed in some COPD patients, whereas body composition analysis is simple and fast. Objective This paper focuses on the correlation between body composition and CPET in patients with COPD, and provides a basis for predicting maximal exercise capacity, formulating rehabilitation prescriptions, and rational nutritional support for patients with COPD who are unable to complete cardiopulmonary exercise testing. Methods Stable COPD patients were enrolled in the outpatient respiratory clinic of China-Japan Friendship Hospital between July 2021 and March 2022, and were sequentially subjected to body composition measurements and CPET with continuous incremental loading, and the test results were analyzed to assess the relationship between body composition and CPET results, and to analyze the value of the body composition indexes in predicting the results of CPET. Results Seventy-seven eligible patients with stable COPD completed body composition measurement and exercise cardiopulmonary exercise testing. Correlation analysis showed that body fat percentage (BFP) was negatively correlated with peak metabolic equivalents (peakMETs) (P

Objective To investigate the effect of tumor-infiltrating B cells on the therapeutic efficacy of programmed death ligand-1 [PD-(L)1] inhibitors and elucidate the potential mechanisms. Methods Based on immunotherapy cohorts for melanoma patients in public databases, the relationship of B cells with progression-free survival (PFS) and response to immune checkpoint inhibitors treatment was analyzed. TC-1 and B16-OVA cells were implanted subcutaneously and in the liver in 6-8-week-old female C57BL/6 mice to establish tumor xenograft models. The effect of B cell clearance on PD-(L)1 therapy was compared. Flow cytometry was performed on the 15th day of TC-1 tumor microenvironment (TME) to confirm the number, function and phenotypic changes of T cells. Flow cytometry and quantitative real-time polymerase chain reaction (qPCR) were used to detect B cell surface molecules and cytokines. Results Based on ERP105482 data from the ICBatlas public database, high CD19 expression in the tumors was associated with longer PFS in melanoma patients (753 vs 95 d, HR=0.3, 95%CI: 0.13~0.65, P=0.003). B cells were significantly enriched in immunotherapy-responsive patients (P=0.01). In a mouse TC-1 liver-loaded tumor model, PD-(L)1 antibody treatment reduced tumor mass (P < 0.01), whereas B-cell clearance attenuated the therapeutic efficacy. B cells enhanced PD-(L)1 antibody treatment by promoting T cell infiltration and function, and the treatment resulted in changes in B cell subsets, as evidenced by an increase in PD-1 low-expressing subsets (P < 0.01). Conclusion After PD-(L)1 treatment, a decrease in PD-1 expression on B cell subsets might be one of the potential mechanisms by which B cells enhance the efficacy of PD-(L)1 therapy.

Gastric precancerous lesions (GPL) are a special histopathological stage before the occurrence of gastric cancer. Effective treatment of GPL is the key to preventing its progression to gastric cancer. GPL has a high level of inflammation in gastric mucosa, and a large number of inflammatory cells, inflammatory factors and inflammatory mediators are metabolized at a high level, which increases oxygen consumption and leads to the formation of a hypoxia microenvironment in gastric mucosa at the GPL stage, which is conducive to the initiation of mitochondrial autophagy and glucose metabolism reprogramming. As a conserved biological process, mitochondrial autophagy exists in various tissues and cells of the body. It can form autophagosome to wrap mitochondria with damaged functions and bind with lysosomes to digest and reuse target mitochondria. Appropriate autophagy level can prevent excessive proliferation of GPL heterotype cells and inhibit the progress of GPL. However, mitochondrial autophagy activity is inhibited during the course of GPL, and the activity of glycometabolic reprogramming into glycolysis is increased during GPL. Glycolysis is a way of energy metabolism in the hypoxia state of cells, which can accelerate the energy supply of cells and the proliferation of abnormal cells, and thus accelerate the deterioration of GPL. Some evidences suggest that there may be a mutually restricting relationship between mitochondrial autophagy and glycolysis reprogramming. The inhibition of autophagy in GPL can increase glycolysis activity on the one hand, while the increase of autophagy inhibits glycolysis activity on the other hand. At present, the specific relationship and mechanism of autophagy and glycolysis are not clear, however, the complex pathological environment of GPL gastric mucosa composed of hypoxia, bacterial infection, inflammation, oxidative stress, activation disorder of signal molecules and other factors may be the key to the low autophagy level and high glycolysis activity. Hypoxia-inducible factor 1α (HIF-1α), which is involved in hypoxia adaptation, is stably expressed in gastric mucosa at the GPL stage and acts as a switch to initiate autophagy and glycolysis. However, HIF-1α seems to be more involved in the regulation of glycolysis in the pathological process of GPL. The cause of this change may be related to the above-mentioned pathological factors. H. pylori infection, activation of phosphoinositide 3-kinase (PI3K)/protein kinase (AKT)/mammalian target of rapamycin (mTOR) pathway and other factors inhibit autophagy. However, the continuous accumulation of reactive oxygen species (ROS) after autophagy inhibition and the aggravation of inflammation caused by H. pylori infection can promote a series of signal interactions and synergies among nuclear factor kappa-B (NF-Κb), signal transducer and activator of transcription 3 (STAT3) and PI3K/AKT/mTOR signaling pathways, and thus indirectly affect HIF-1α to promote glycolysis or directly improve glycolysis level. HIF-1α may be more involved in the activation of glycolysis due to the regulation of GPL pathological microenvironment and its upstream complex signals, thus unable to fully activate BNIP-3 mediated hypoxia-initiated autophagy, leading to the down-regulation or inhibition of autophagy level, and the inhibition of autophagy indirectly promotes the improvement of glycolysis level, forming a vicious cycle, and ultimately leading to the deterioration of GPL. This article reviewed the research progress of hypoxia-induced mitochondrial autophagy and glucose metabolism reprogramming in gastric precancerous lesions.

Abstract Stroke is a group of major diseases that cause death or disability in adults, with high incidence and lack of available therapeutic strategies. Although traditional Chinese medicine (TCM) has continuously achieved good effects in the therapy of stroke while there is still not convincing due to the limitation of blood–brain permeability, as well as the individual differences in usage and dosage. With the improvement of nanotechnology, TCM nanopreparation has gradually become a research hotspot in various fields due to its advantages in permeating the blood–brain barrier, targeting delivery, enhancing sustained‐release drug delivery, changing the distribution in the body, and improving bioavailability. Zeolitic imidazolate framework‐8 (ZIF‐8) is an ideal nano‐drug delivery system for adsorption, catalysis, and drug loading, which is a biocompatible metal–organic framework framed by 2‐methylimidazole and zinc ions. At present, ZIF‐8 was wildly used in the treatment of ischemic stroke. However, challenges remain persists for its clinical application, such as preparation technology, detection technology in vivo, targeting specificity, safety and stability, and so forth. Therefore, more efforts need to overcome the above problems to develop the application of TCM nanopreparations in the therapy of ischemia/reperfusion in the future.

Aim: We aimed to investigate the long‐term influence of a diet and/or exercise intervention on long‐term mortality and cardiovascular disease (CVD) events. Methods: The Da Qing Diabetes Prevention Study had 576 participants with impaired glucose tolerance (IGT) randomized to diet‐only, exercise‐only and diet‐plus‐exercise intervention group and control group. The participants underwent lifestyle interventions for 6 years. The subsequent Da Qing Diabetes Prevention Outcome Study was a prospective cohort study to follow‐up the participants for up to 24 years after the end of 6‐year intervention. In total, 540 participants completed the follow‐up, while 36 subjects lost in follow‐up. Cox proportional hazards analysis was applied to assess the influence of lifestyle interventions on targeted outcomes. Results: Compared with controls, the diet‐only intervention in people with IGT was significantly associated with a reduced risk of all‐cause death [hazard ratio (HR) 0.77, 95% confidence interval (CI) (0.61‐0.97)], CVD death [HR 0.67, 95% CI (0.46‐0.97)] and CVD events [HR 0.72, 95% CI (0.54‐0.96)]. The diet‐plus‐exercise intervention was significantly associated with a decreased risk of all‐cause death [HR 0.64, 95% CI (0.48‐0.84)], CVD death [HR 0.54, 95% CI (0.30‐0.97)] and CVD events [HR 0.68, 95% CI (0.52‐0.90)]. Unexpectedly, the exercise‐only intervention was not significantly associated with the reduction of any of these outcomes, although there was a consistent trend towards reduction. Conclusions: A diet‐only intervention and a diet‐plus‐exercise intervention in people with IGT were significantly associated with a reduced risk of all‐cause death, CVD death and CVD events, while an exercise‐only intervention was not. It suggests that diet‐related interventions may have a potentially more reliable influence on long‐term vascular complications and mortality. [ABSTRACT FROM AUTHOR]

Background: High medication burdens are common in patients with chronic obstructive pulmonary disease (COPD). This study aimed to explore the associations of medication regimen complexity index (MRCI) with medication adherence and clinical outcomes among patients with acute exacerbations of COPD (AECOPD) after hospital discharge. Methods: Data were obtained from a nationwide cohort study of inpatients with AECOPD in China. MRCI scores were calculated using the medication list 30 days after discharge and separated into COPD-specific and non-COPD MRCI scores. Medication adherence was measured by the withdrawal rate of COPD or inhaled long-acting bronchodilators 6 months after discharge. Clinical outcomes included re-exacerbations and COPD-related readmissions during the 30-day to 6-month follow-up period. The associations of MRCI with medication withdrawal and clinical outcomes were evaluated using univariate and multivariate logistic regressions. Potential covariates included sociodemographic factors, year of COPD diagnosis, post-bronchodilator percentage predicted forced expiratory volume in 1 s, mMRC score, CAT score, and comorbidities. Results: Among the 2853 patients included, the median total MRCI score was 7 [interquartile range (IQR), 7−13]. A high MRCI score (>7) was presented in 1316 patients (46.1%). Of the MRCI score, 91% were COPD specific. The withdrawal rates of the COPD and inhaled long-acting bronchodilators were 24.2% and 24.4%, respectively. Re-exacerbation and COPD-related readmission rates were 10.2% and 7.5%, respectively. After adjusting for covariates, patients with high total MRCI scores were less likely to discontinue COPD drugs [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.52−0.74] and inhaled long-acting bronchodilators (OR, 0.68; 95%CI, 0.57−0.81); conversely, these patients were more likely to experience re-exacerbation (OR, 1.64; 95% CI, 1.27−2.11) and readmission (OR, 1.57; 95% CI, 1.17−2.10). Conclusion: MRCI scores were relatively low among post-hospitalized patients with AECOPD in China. Higher MRCI scores were positively associated with adherence to COPD or inhaled medications, and risk of re-exacerbation and readmission. Registration: ClinicalTrials.gov identifier: NCT02657525. [ABSTRACT FROM AUTHOR]

Amentoflavone (AF) is a natural multifunctional biflavonoid that has been revealed to possess multiple biological activities, including anticancer activity. Here, this work focused on exploring the functions and mechanism of AF in gastric cancer (GC). Levels of genes and proteins were examined by quantitative real‐time PCR and western blotting. Cell proliferation and cell death were analyzed using cell counting kit‐8, colony formation, and lactate dehydrogenase (LDH) release assay, respectively. Cell ferroptosis was evaluated by detecting the levels of malondialdehyde (MDA), reduced glutathione (GSH), Fe2+, and intracellular reactive oxygen species (ROS). The binding between miR‐496 and activating transcription factor 2 (ATF2) was confirmed by using dual‐luciferase reporter assay. Murine xenograft assay was conducted for in vivo experiments. The results showed that AF suppressed the proliferation and induced ferroptotic cell death in GC cells. MiR‐496 expression was decreased in GC tissues and cells, and AF treatment increased miR‐496 expression level in GC cells. Functionally, miR‐496 inhibition reversed the inhibitory effects of AF on GC cell proliferation and promoting effects on ferroptotic cell death. Mechanistically, ATF2 was targeted by miR‐496. ATF2 expression was increased in GC tissues and cells, which was decreased by AF treatment and subsequently rescued by miR‐496 downregulation in GC cells. Moreover, miR‐496 overexpression suppressed the proliferation and induced ferroptotic cell death in GC cells via targeting ATF2. In all, AF suppressed the proliferation and induced ferroptotic cell death in GC cells via miR‐496/ATF2 axis, indicating a novel therapeutic approach for GC patients. [ABSTRACT FROM AUTHOR]