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1.
Association between BMI and Efficacy of SGLT2 Inhibitors in Patients with Heart Failure or at Risk of Heart Failure: A Meta-Analysis Based on Randomized Controlled Trials.
Zhou, Y, Dai, M, Huang, T, Chen, B, Xiang, Z, Tang, J, Zheng, M, Guo, L
Cardiology. 2024;(2):104-116
Abstract
INTRODUCTION This meta-analysis aimed to investigate the effect of SGLT2 inhibitors on the prognosis of patients with heart failure (HF) or at risk of HF across different body mass index (BMI). METHODS We searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials comparing SGLT2 inhibitors with placebo in patients with HF or at risk of HF and extracted relevant data up to April 2023 for meta-analysis. RESULTS A total of 29,500 patients were enrolled in the selected five studies. The results showed that patients treated with SGLT2 inhibitors had lower HF hospitalization (HHF) or cardiovascular (CV) mortality compared to those taking placebo (hazard ratio [HR] = 0.73, p < 0.001). Patients taking SGLT2 inhibitors also had a lower all-cause mortality rate than those taking placebo (HR = 0.85, p = 0.017). In BMI subgroup analysis, the HHF rate in the experimental group was lower than that in the control group at BMI ≤24.9 kg/m2, 25.0-29.9 kg/m2, and ≥30.0 kg/m2. There was no significant difference in CV mortality between the two groups at BMI ≤24.9 kg/m2 (HR = 0.91, p = 0.331) and 25.0-29.9 kg/m2 (HR = 0.92, p = 0.307). However, when the BMI was ≥30.0 kg/m2, CV mortality with SGLT2 inhibitors was lower than in the control group (HR = 0.79, p = 0.002). When patients had a BMI ≤24.9 kg/m2 (HR = 0.85, p = 0.033) and 25.0-29.9 kg/m2 (HR = 0.83, p = 0.046), the all-cause mortality was lower in the experimental group than in the control group. However, there was no significant difference between the 2 groups in patients with a BMI ≥30.0 kg/m2 (HR = 0.87, p = 0.094). CONCLUSION SGLT2 inhibitors improve the prognosis in patients with HF or at risk of HF. This effect is affected by BMI.
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2.
Divergent rhizosphere and non-rhizosphere soil microbial structure and function in long-term warmed steppe due to altered root exudation.
Yu, Y, Zhou, Y, Janssens, IA, Deng, Y, He, X, Liu, L, Yi, Y, Xiao, N, Wang, X, Li, C, et al
Global change biology. 2024;(1):e17111
Abstract
While there is an extensive body of research on the influence of climate warming on total soil microbial communities, our understanding of how rhizosphere and non-rhizosphere soil microorganisms respond to warming remains limited. To address this knowledge gap, we investigated the impact of 4 years of soil warming on the diversity and composition of microbial communities in the rhizosphere and non-rhizosphere soil of a temperate steppe, focusing on changes in root exudation rates and exudate compositions. We used open top chambers to simulate warming conditions, resulting in an average soil temperature increase of 1.1°C over a span of 4 years. Our results showed that, in the non-rhizosphere soil, warming had no significant impact on dissolved organic carbon concentrations, compositions, or the abundance of soil microbial functional genes related to carbon and nitrogen cycling. Moreover, soil microbial diversity and community composition remained largely unaffected, although warming resulted in increased complexity of soil bacteria and fungi in the non-rhizosphere soil. In contrast, warming resulted in a substantial decrease in root exudate carbon (by 19%) and nitrogen (by 12%) concentrations and induced changes in root exudate compositions, primarily characterized by a reduction in the abundance in alcohols, coenzymes and vitamins, and phenylpropanoids and polyketides. These changes in root exudation rates and exudate compositions resulted in significant shifts in rhizosphere soil microbial diversity and community composition, ultimately leading to a reduction in the complexity of rhizosphere bacterial and fungal community networks. Altered root exudation and rhizosphere microbial community composition therefore decreased the expression of functional genes related to soil carbon and nitrogen cycling. Interestingly, we found that changes in soil carbon-related genes were primarily driven by the fungal communities and their responses to warming, both in the rhizosphere and non-rhizosphere soil. The study of soil microbial structure and function in rhizosphere and non-rhizosphere soil provides an ideal setting for understanding mechanisms for governing rhizosphere and non-rhizosphere soil carbon and nitrogen cycles. Our results highlight the distinctly varied responses of soil microorganisms in the rhizosphere and non-rhizosphere soil to climate warming. This suggests the need for models to address these processes individually, enabling more accurate predictions of the impacts of climate change on terrestrial carbon cycling.
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3.
Heartache and Heartbreak: An Observational and Mendelian Randomization Study.
Cai, D, Xia, M, Chen, X, Yagi, K, Xu, L, Wang, B, Wang, Y, Zhou, Y, Liu, J
Global heart. 2024;(1):19
Abstract
BACKGROUND Depression has a significant effect on cardiovascular disease (CVD), but uncertainties persist regarding which modifiable risk factors mediate the causal effects. We aim to determine whether depression is causally linked to CVD and which modifiable risk factors play potential mediating roles. METHODS We used a two-sample Mendelian randomization (MR) approach and NHANES 2007-2018 data to estimate the effects of depression on various CVD cases and investigated 28 potential mediators of the association between depression and CVD. RESULTS The results of our MR analysis indicated that genetically determined depression was associated with increased risk of several CVD, including coronary heart disease (odds ratio (OR) = 1.14; 95% confidence interval (CI): 1.05,1.22), myocardial infarction (OR = 1.19; 95% CI, 1.09,1.31), atrial fibrillation (OR = 1.14; 95% CI, 1.06,1.22), and stroke (OR = 1.13; 95% CI, 1.05,1.22). However, there was no causal association between depression and heart failure. Four out of 28 cardiometabolic risk factors, including hyperlipidemia, hypertension, diabetes, and prescription opioid use, were identified as mediators of the association between depression and various CVDs. Observational association analyses from NHANES data yielded consistent results. CONCLUSION Our findings demonstrated that depression has a causal detrimental effect on various CVDs. Four causal mediators (hyperlipidemia, hypertension, diabetes, and prescription opioid use) were screened to explain the causal effect. Implementing targeted management strategies for these risk factors may be warranted to mitigate the public health burden of CVD among individuals with depression.
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4.
Organismal Function Enhancement through Biomaterial Intervention.
Tian, F, Zhou, Y, Ma, Z, Tang, R, Wang, X
Nanomaterials (Basel, Switzerland). 2024;(4)
Abstract
Living organisms in nature, such as magnetotactic bacteria and eggs, generate various organic-inorganic hybrid materials, providing unique functionalities. Inspired by such natural hybrid materials, researchers can reasonably integrate biomaterials with living organisms either internally or externally to enhance their inherent capabilities and generate new functionalities. Currently, the approaches to enhancing organismal function through biomaterial intervention have undergone rapid development, progressing from the cellular level to the subcellular or multicellular level. In this review, we will concentrate on three key strategies related to biomaterial-guided bioenhancement, including biointerface engineering, artificial organelles, and 3D multicellular immune niches. For biointerface engineering, excess of amino acid residues on the surfaces of cells or viruses enables the assembly of materials to form versatile artificial shells, facilitating vaccine engineering and biological camouflage. Artificial organelles refer to artificial subcellular reactors made of biomaterials that persist in the cytoplasm, which imparts cells with on-demand regulatory ability. Moreover, macroscale biomaterials with spatiotemporal regulation characters enable the local recruitment and aggregation of cells, denoting multicellular niche to enhance crosstalk between cells and antigens. Collectively, harnessing the programmable chemical and biological attributes of biomaterials for organismal function enhancement shows significant potential in forthcoming biomedical applications.
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5.
Tenapanor in Chinese ESRD patients with hyperphosphatemia on haemodialysis: a randomised, phase 3 trial.
Gan, L, Xing, L, Xu, Y, Zhou, L, Jiang, H, Sun, X, Guan, T, Luo, P, Wang, J, Sun, F, et al
Clinical kidney journal. 2024;(1):sfad216
Abstract
BACKGROUND The efficacy and safety of tenapanor has not been confirmed in Chinese end-stage renal disease (ESRD) patients with hyperphosphatemia on haemodialysis (HD). METHODS This was a randomised, double blind, phase 3 trial conducted at 26 dialysis facilities in China (https://www.chictr.org.cn/index.aspx; CTR20202588). After a 3-week washout, adults with ESRD on HD with hyperphosphatemia were randomised (1:1) using an interactive web response system to oral tenapanor 30 mg twice a day or placebo for 4 weeks. The primary endpoint was the change in mean serum phosphorous level from baseline to the endpoint visit (day 29 or last serum phosphorus measurement). Efficacy was analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drug. RESULTS Between 5 March 2021 and 8 June 2022, 77 patients received tenapanor and 73 received placebo. Tenapanor treatment (n = 75) resulted in a significantly greater least squares (LS) mean reduction in serum phosphate at the endpoint visit versus placebo (n = 72): LS mean difference -1.17 mg/dl (95% CI -1.694 to -0.654, P < .001). More patients receiving tenapanor achieved a serum phosphorous level <5.5 mg/dl at the endpoint visit (44.6% versus 10.1%). The most common treatment-related adverse event was diarrhoea [tenapanor 28.6% (22/77), placebo 2.7% (2/73)], which was mostly mild and led to treatment discontinuation in two patients receiving tenapanor. CONCLUSIONS Tenapanor significantly reduced the serum phosphorous level versus placebo in Chinese ESRD patients on HD and was generally well tolerated.
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6.
Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis.
Cao, L, An, Y, Liu, H, Jiang, J, Liu, W, Zhou, Y, Shi, M, Dai, W, Lv, Y, Zhao, Y, et al
BMC medicine. 2024;(1):101
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.
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7.
Nanotechnology Reprogramming Metabolism for Enhanced Tumor Immunotherapy.
Zhou, Y, Yuan, J, Xu, K, Li, S, Liu, Y
ACS nano. 2024;(3):1846-1864
Abstract
Mutation burden, hypoxia, and immunoediting contribute to altered metabolic profiles in tumor cells, resulting in a tumor microenvironment (TME) characterized by accumulation of toxic metabolites and depletion of various nutrients, which significantly hinder the antitumor immunity via multiple mechanisms, hindering the efficacy of tumor immunotherapies. In-depth investigation of the mechanisms underlying these phenomena are vital for developing effective antitumor drugs and therapies, while the therapeutic effects of metabolism-targeting drugs are restricted by off-target toxicity toward effector immune cells and high dosage-mediated side effects. Nanotechnologies, which exhibit versatility and plasticity in targeted delivery and metabolism modulation, have been widely applied to boost tumor immunometabolic therapies via multiple strategies, including targeting of metabolic pathways. In this review, recent advances in understanding the roles of tumor cell metabolism in both immunoevasion and immunosuppression are reviewed, and nanotechnology-based metabolic reprogramming strategies for enhanced tumor immunotherapies are discussed.
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8.
Key candidate genes and pathways in T lymphoblastic leukemia/lymphoma identified by bioinformatics and serological analyses.
Ren, Y, Liang, H, Huang, Y, Miao, Y, Li, R, Qiang, J, Wu, L, Qi, J, Li, Y, Xia, Y, et al
Frontiers in immunology. 2024;:1341255
Abstract
T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL) is an uncommon but highly aggressive hematological malignancy. It has high recurrence and mortality rates and is challenging to treat. This study conducted bioinformatics analyses, compared genetic expression profiles of healthy controls with patients having T-ALL/T-LBL, and verified the results through serological indicators. Data were acquired from the GSE48558 dataset from Gene Expression Omnibus (GEO). T-ALL patients and normal T cells-related differentially expressed genes (DEGs) were investigated using the online analysis tool GEO2R in GEO, identifying 78 upregulated and 130 downregulated genes. Gene Ontology (GO) and protein-protein interaction (PPI) network analyses of the top 10 DEGs showed enrichment in pathways linked to abnormal mitotic cell cycles, chromosomal instability, dysfunction of inflammatory mediators, and functional defects in T-cells, natural killer (NK) cells, and immune checkpoints. The DEGs were then validated by examining blood indices in samples obtained from patients, comparing the T-ALL/T-LBL group with the control group. Significant differences were observed in the levels of various blood components between T-ALL and T-LBL patients. These components include neutrophils, lymphocyte percentage, hemoglobin (HGB), total protein, globulin, erythropoietin (EPO) levels, thrombin time (TT), D-dimer (DD), and C-reactive protein (CRP). Additionally, there were significant differences in peripheral blood leukocyte count, absolute lymphocyte count, creatinine, cholesterol, low-density lipoprotein, folate, and thrombin times. The genes and pathways associated with T-LBL/T-ALL were identified, and peripheral blood HGB, EPO, TT, DD, and CRP were key molecular markers. This will assist the diagnosis of T-ALL/T-LBL, with applications for differential diagnosis, treatment, and prognosis.
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9.
Early enteral nutrition versus early supplemental parenteral nutrition in patients undergoing major abdominal surgery: a secondary analysis of 2 randomized clinical trials.
Gao, X, Zhang, Y, Qi, X, Xiao, Y, Gao, T, Jin, G, Wang, K, Zhou, Y, Chi, Q, Yang, H, et al
The American journal of clinical nutrition. 2024;(4):1036-1043
Abstract
BACKGROUND The effect of early isoenergetic feeding routes [early enteral nutrition (E-EN) or early supplemental parenteral nutrition (E-SPN)] on the outcome of patients undergoing major abdominal surgery is controversial. OBJECTIVES The aim of this study was to investigate the impact of early isoenergetic EN compared with early isoenergetic SPN on nosocomial infections in patients undergoing major abdominal surgery. METHODS This study is a secondary, post hoc analysis of data from 2 open-label randomized clinical trials. Participants were recruited from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and with Nutritional Risk Screening 2002 score ≥3. All eligible patients were categorized into 2 groups based on their achievement of the 100% energy target on postoperative day (POD) 3: the E-EN group (n = 199) and the E-SPN group (n = 115). The primary outcome was the incidence of nosocomial infections between POD 3 and hospital discharge. RESULTS In total, 314 patients [mean (SD) age, 59.2 (11.4) y; 113 (36.0%) females] were included. Patients in the E-EN group showed no significant difference in nosocomial infections compared with those in the E-SPN group {17/199 [8.5%] compared with 10/115 [8.7%], risk difference, 0.2% [95% confidence interval (CI): -6.3, 6.6]}. The hematological nutritional status of the E-EN group showed a significant improvement at discharge compared with the E-SPN group (albumin: 38.0 ± 6.0 g/L compared with 35.5 ± 7.6 g/L; mean difference, -2.5 g/L; 95% CI: -4.0, -1.0 g/L; prealbumin: 200.0 ± 8.0 mg/L compared with 158.4 ± 38.1 mg/L; mean difference, -41.6 mg/L; 95% CI: -41.7, -36.1 mg/L). Other indicators were comparable between groups. CONCLUSION E-EN compared with isoenergetic SPN may not be associated with a reduced rate of nosocomial infection in patients undergoing major abdominal surgery, but may be associated with improved hematological nutritional status. TRIAL REGISTRATION NUMBER This trial was registered at clinicaltrials.gov as NCT03115957 (https://clinicaltrials.gov/ct2/show/NCT03115957) and NCT03117348 (https://clinicaltrials.gov/ct2/show/NCT03117348).
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10.
The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.
Zhuang, Q, Liao, A, He, Q, Liu, C, Zheng, C, Li, X, Liu, Y, Wang, B, Liu, S, Zhang, Y, et al
Journal of gastroenterology and hepatology. 2024;(4):658-666
Abstract
BACKGROUND AND AIM Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.