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Body mass index and weight loss as risk factors for poor outcomes in patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.
He, X, Ji, J, Liu, C, Luo, Z, Tang, J, Yan, H, Guo, L
Annals of medicine. 2024;(1):2311845
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Abstract
OBJECTIVE The association between nutritional status and prognosis of idiopathic pulmonary fibrosis (IPF) remains unclear. This systematic review and meta-analysis aimed to explore the effect of body mass index (BMI) and weight loss on the prognosis of IPF patients. METHODS We accumulated studies on IPF, BMI, and weight loss from databases including PubMed, Embase, Web of science, Scopus, Ovid and Cochrane Library up to 4 August 2023. Using Cox proportional hazard regression model for subgroup analysis, hazard ratio (HR) and 95% confidence intervals (CI) for BMI in relation to mortality, acute exacerbation (AE), and hospitalization in IPF patients were calculated, and HR, odds ratio (OR), and 95% CI for weight loss corresponding to IPF patient mortality were assessed. Sensitivity analysis was peformed by eliminating every study one by one, and publication bias was judged by Egger's test and trim-and-fill method. RESULTS A total of 34 eligible studies involving 18,343 IPF patients were included in the meta-analysis. The pooled results by univariate Cox regression analysis showed that baseline BMI was a predictive factor for IPF mortality (HR = 0.93, 95%CI = [0.91, 0.94]). Furthermore, the results by the multivariable regression model indicated that baseline BMI was an independent risk factor for predicting IPF mortality (HR = 0.94, 95%CI = [0.91, 0.98]). Weight loss was identified as a risk factor for IPF mortality (HR = 2.74, 95% CI = [2.12, 3.54]; OR = 4.51, 95% CI = [1.72, 11.82]) and there was no predictive value of BMI for acute exacerbation (HR = 1.00, 95% CI= [0.93, 1.07]) or hospitalization (HR = 0.95, 95% CI = [0.89, 1.02]). CONCLUSION Low baseline BMI and weight loss in the course of IPF may indicate a high risk of mortality in patients with IPF, so it is meaningful to monitor and manage the nutritional status of IPF patients, and early intervention should be conducted for low BMI and weight loss.
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Exploring the therapeutic potential of tetrahydrobiopterin for heart failure with preserved ejection fraction: A path forward.
Xia, W, Zhang, M, Liu, C, Wang, S, Xu, A, Xia, Z, Pang, L, Cai, Y
Life sciences. 2024;:122594
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Abstract
A large number of patients are affected by classical heart failure (HF) symptomatology with preserved ejection fraction (HFpEF) and multiorgan syndrome. Due to high morbidity and mortality rate, hospitalization and mortality remain serious socioeconomic problems, while the lack of effective pharmacological or device treatment means that HFpEF presents a major unmet medical need. Evidence from clinical and basic studies demonstrates that systemic inflammation, increased oxidative stress, and impaired mitochondrial function are the common pathological mechanisms in HFpEF. Tetrahydrobiopterin (BH4), beyond being an endogenous co-factor for catalyzing the conversion of some essential biomolecules, has the capacity to prevent systemic inflammation, enhance antioxidant resistance, and modulate mitochondrial energy production. Therefore, BH4 has emerged in the last decade as a promising agent to prevent or reverse the progression of disorders such as cardiovascular disease. In this review, we cover the clinical progress and limitations of using downstream targets of nitric oxide (NO) through NO donors, soluble guanylate cyclase activators, phosphodiesterase inhibitors, and sodium-glucose co-transporter 2 inhibitors in treating cardiovascular diseases, including HFpEF. We discuss the use of BH4 in association with HFpEF, providing new evidence for its potential use as a pharmacological option for treating HFpEF.
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Domain of unknown function (DUF) proteins in plants: function and perspective.
Luo, C, Akhtar, M, Min, W, Bai, X, Ma, T, Liu, C
Protoplasma. 2024;(3):397-410
Abstract
Domains of unknown function (DUFs), which are deposited in the protein family database (Pfam), are protein domains with conserved amino acid sequences and uncharacterized functions. Proteins with the same DUF were classified as DUF families. Although DUF families are generally not essential for the survival of plants, they play roles in plant development and adaptation. Characterizing the functions of DUFs is important for deciphering biological puzzles. DUFs were generally studied through forward and reverse genetics. Some novelty approaches, especially the determination of crystal structures and interaction partners of the DUFs, should attract more attention. This review described the identification of DUF genes by genome-wide and transcriptome-wide analyses, summarized the function of DUF-containing proteins, and addressed the prospects for future studies in DUFs in plants.
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Role of ferroptosis in chronic kidney disease.
Li, S, Han, Q, Liu, C, Wang, Y, Liu, F, Pan, S, Zuo, L, Gao, D, Chen, K, Feng, Q, et al
Cell communication and signaling : CCS. 2024;(1):113
Abstract
Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment. Video Abstract.
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Interventions for Postextubation Dysphagia in Critically Ill Patients: A Systematic Review and Meta-analysis.
Chen, L, Liu, C, Yuan, M, Yin, X, Niu, S, Tang, J, Chen, H, Xiong, B, Feng, X
Dysphagia. 2024
Abstract
OBJECTIVE This review evaluates the efficacy and safety of dysphagia interventions for patients with prolonged endotracheal intubation (⩾48 h) in critical care units. DATA SOURCES We systematically searched PubMed, Cochrane Library, Medline, Embase, OVID, CINAHL, Wanfang (China), CNKI (China), and ProQuest Dissertations for studies published up to December 31, 2023. STUDY SELECTION Inclusion criteria encompassed randomized controlled trials (RCTs), quasi-randomized trials, and cohort studies comparing dysphagia rehabilitation - such as swallowing stimulation, swallowing and respiratory muscle exercise, and neuromuscular electrical stimulation - with standard care or no treatment. The primary outcomes assessed were dysphagia severity, time to resume oral intake, and incidence of aspiration and aspiration pneumonia. DATA EXTRACTION Detailed information on study design, setting, participant demographics, interventions, and outcomes was systematically extracted. DATA SYNTHESIS Our analysis included ten studies with a total of 1031 participants. The findings demonstrate a significant reduction in dysphagia severity, time to oral intake and the risk of aspiration pneumonia, and an improvement in quality of life among patients receiving swallowing therapy. However, no substantial difference was found in nutritional status. Limited data availability necessitated a descriptive presentation of outcomes like the risk of aspiration, ICU/hospital stay duration, pharyngeal/oral residue severity, and intervention-related adverse events. CONCLUSION The current evidence for the effectiveness of dysphagia interventions in critically ill patients with prolonged endotracheal intubation is limited. There is a pressing need for future research, particularly high-quality RCTs employing standardized outcome measures, to substantiate these findings.
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Exposures to drinking water disinfection byproducts and kidney function in Chinese women.
Li, CR, Deng, YL, Miao, Y, Zhang, M, Zeng, JY, Liu, XY, Wu, Y, Li, YJ, Liu, AX, Zhu, JQ, et al
Environmental research. 2024;:117925
Abstract
BACKGROUND Disinfection byproducts (DBPs), the ubiquitous contaminants in drinking water, have been shown to impair renal function in experimental studies. However, epidemiological evidence is sparse. OBJECTIVE To investigate exposures to DBPs in associations with renal function among women. METHODS A total of 920 women from December 2018 to January 2020 were abstracted from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort study in Wuhan, China. Urine samples were gathered at baseline recruitment and analyzed for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. Serum uric acid (UA), creatinine, and estimated glomerular filtration rate (eGFR) were measured as indicators of renal function. Multivariate linear regression and restricted cubic spline (RCS) models were conducted to assess urinary DCAA and TCAA concentrations in associations with renal function indicators. Stratified analyses by age and body mass index (BMI) were also performed. RESULTS We found null evidence of urinary TCAA in associations with renal function indicators. However, elevated urinary DCAA tertiles were related to decreased eGFR (β = -1.78%, 95% CI: 3.21%, -0.36%, comparing the upper vs. lower tertile; P for trend = 0.01). This inverse association still existed when urinary DCAA concentration was treated as a continuous variable, and the dose-response relationship was linear based on the RCS model (P for overall association = 0.002 and P for non-linear associations = 0.44). In the stratified analyses, we found an association of urinary DCAA concentration with decreased UA level among women <30 years but an association with increased UA level among women ≥30 years (P for interaction = 0.04). CONCLUSION Urinary DCAA but not TCAA was associated with impaired renal function among women undergoing assisted reproductive technology.
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Global burden and risk factors of gastritis and duodenitis: an observational trend study from 1990 to 2019.
Liu, Y, Zhang, J, Guo, Y, Tian, S, Wu, Y, Liu, C, Huang, X, Zhang, S, Dong, W
Scientific reports. 2024;(1):2697
Abstract
In recent years, there has been a global trend of aging, which has resulted in significant changes to the burden of gastritis and duodenitis (GD). Using the global burden of disease (GBD) database spanning 1990 to 2019, we evaluated the temporal trends of age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and age-standardized disability-adjusted life years (AS-DALYs) for GD using estimated annual percentage changes (EAPC). Additionally, we examined the burden of GD across various strata, including social demographic index (SDI), age, and sex. Finally, the risk factors linked to the incidence and mortality of GD, utilizing Pearson correlation analysis. In 2019, there were 31 million GD patients globally, a notable increase of 12 million from 1990, while the ASIR, ASDR, and AS-DALYs for GD all showed a decrease. Correlation analysis showed a significant negative relationship between ASIR and SDI. Factors like hand hygiene and vitamin A deficiency had significant positive correlations with ASIR and ASDR in 2019. Over the past thirty years, the burden of GD has increased alongside global population aging. Future efforts should focus on exploring prevention for GD, with special attention to the elderly population in low SDI regions.
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Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma.
Wang, J, Liu, C, Hu, R, Wu, L, Li, C
Frontiers in pharmacology. 2024;:1324140
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and accounts for more than 90% of primary liver cancer. The advent of immune checkpoint inhibitor (ICI)-related therapies combined with angiogenesis inhibition has revolutionized the treatment of HCC in late-stage and unresectable HCC, as ICIs alone were disappointing in treating HCC. In addition to the altered immune microenvironment, abnormal lipid metabolism in the liver has been extensively characterized in various types of HCC. Stains are known for their cholesterol-lowering properties and their long history of treating hypercholesterolemia and reducing cardiovascular disease risk. Apart from ICI and other conventional therapies, statins are frequently used by advanced HCC patients with dyslipidemia, which is often marked by the abnormal accumulation of cholesterol and fatty acids in the liver. Supported by a body of preclinical and clinical studies, statins may unexpectedly enhance the efficacy of ICI therapy in HCC patients through the regulation of inflammatory responses and the immune microenvironment. This review discusses the abnormal changes in lipid metabolism in HCC, summarizes the clinical evidence and benefits of stain use in HCC, and prospects the possible mechanistic actions of statins in transforming the immune microenvironment in HCC when combined with immunotherapies. Consequently, the use of statin therapy may emerge as a novel and valuable adjuvant for immunotherapies in HCC.
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The lipid droplet in cancer: From being a tumor-supporting hallmark to clinical therapy.
Cui, Y, Man, S, Tao, J, Liu, Y, Ma, L, Guo, L, Huang, L, Liu, C, Gao, W
Acta physiologica (Oxford, England). 2024;(3):e14087
Abstract
INTRODUCTION Abnormal lipid metabolism, one of the hallmarks in cancer, has gradually emerged as a novel target for cancer treatment. As organelles that store and release excess lipids, lipid droplets (LDs) resemble "gears" and facilitate cancer development in the body. AIM: This review discusses the life cycle of LDs, the relationship between abnormal LDs and cancer hallmarks, and the application of LDs in theragnostic and clinical contexts to provide a contemporary understanding of the role of LDs in cancer. METHODS A systematic literature search was conducted in PubMed and SPORTDiscus. Retrieve and summarize clinical trials of drugs that target proteins associated with LD formation using the Clinical Trials website. Create a schematic diagram of lipid droplets in the tumor microenvironment using Adobe Illustrator. CONCLUSION As one of the top ten hallmarks of cancer, abnormal lipid metabolism caused by excessive generation of LDs interrelates with other hallmarks. The crosstalk between excessive LDs and intracellular free fatty acids (FFAs) promotes an inflammatory environment that supports tumor growth. Moreover, LDs contribute to cancer metastasis and cell death resistance in vivo. Statins, as HMGCR inhibitors, are promising to be the pioneering commercially available anti-cancer drugs that target LD formation.
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Bioequivalence and Safety Assessment of 2 Formulations of Low-Dose Metformin Hydrochloride under Fasting Conditions in Healthy Chinese Participants: A Randomized Phase 1 Clinical Trial.
Sun, ML, Xu, XW, Liu, C, Tong, YX, Wei, YL, Liu, HJ, Zhang, W, Wang, XH
Clinical pharmacology in drug development. 2024;(3):307-314
Abstract
The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open-label, single-dose, 2-period, 2-sequence crossover, single-center, randomized phase I clinical trial. T and R were considered bioequivalent if the adjusted geometric mean ratios (GMRs) and 90% confidence intervals of the area under the curve (AUC) and maximum concentration (Cmax ) were within the range of 0.8-1.25. Thirty-five participants completed the trial. The T/R adjusted GMRs (95.7% for Cmax , 98.7% for AUC0→t , 98.8% for AUC0→∞ ) were within the acceptable bioequivalence range of 80%-125%. No serious adverse events or suspected or unexpected serious adverse reactions occurred during this trial. The study findings confirmed that generic MH is a well-tolerated and bioequivalent alternative to innovative products under fasting conditions in healthy Chinese participants. (www.chinadrugtrials.org.cn; registration no. CTR20190356).