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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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Safety and efficacy of melatonin supplementation as an add-on treatment for infantile epileptic spasms syndrome: A randomized, placebo-controlled, double-blind trial.
Sun, Y, Chen, J, Shi, X, Li, Z, Wan, L, Yan, H, Chen, Y, Wang, J, Wang, J, Zou, L, et al
Journal of pineal research. 2024;(1):e12922
Abstract
This was a prospective, randomized, double-blind, single-center placebo-controlled trial to assess the efficacy and safety of melatonin as an add-on treatment for infantile epileptic spasms syndrome (IESS). Participants aged 3 months to 2 years with a primary diagnosis of IESS were recruited and assigned to two groups in a 1:1 ratio. Both treatment groups received a combination of adrenocorticotrophic hormone (ACTH) and magnesium sulfate (MgSO4 ) for 2 weeks, and the treatment group also received melatonin (3 mg) between 20:00 and 21:00 daily, 0.5-1 h before bedtime. The study's primary endpoint was the average reduction rate in spasm frequency assessed by seizure diaries. Secondary endpoints included assessment of the response rate, EEG hypsarrhythmia (Kramer score), and psychomotor development (Denver Developmental Screening Test, DDST). Sleep quality was assessed by using the Brief Infant Sleep Questionnaire (BISQ), the Infant Sleep Assessment Scale (ISAS), and actigraphy. Safety parameters were also evaluated. Statistical analyses were conducted on intention-to-treat and per-protocol populations. The trial is registered at Clinicaltrials.gov (ChiCTR2000036208). Out of 119 screened patients, 70 were randomized and 66 completed treatments. In the intention-to-treat population, there were no significant differences in the average percentage reduction of spasm frequency (median [interquartile range, IQR: Q3-Q1], 100% [46.7%] vs. 66.7% [55.3%], p = .288), the 3-day response rate (51.4% vs. 37.1%, p = .229), the 28-day response rate (42.9% vs. 28.6%, p = .212), EEG Kramer scores (2 [3.5] vs. 2 [3], p = .853), or DDST comprehensive months (5 [2.5] vs. 6 [6], p = .239) between the melatonin (n = 35) and placebo (n = 35) groups. However, caregivers reported improved sleep quality after melatonin treatment, with 85.7% reporting regular sleep compared to 42.9% with placebo (42.9%, p < .001). The melatonin group had lower ISAS scores in 4-11-month-old patients compared to the placebo (mean ± SD, 29.3 ± 4.4 vs. 35.2 ± 5.9, p < .001). Moreover, the median (IQR) value of sleep-onset latency was shortened by 6.0 (24.5) min after melatonin treatment, while that in the placebo group was extended by 3.0 (22.0) min (p = .030). The serum melatonin (6:00 h) level (pg/mL) of the children in the melatonin group after treatment was significantly higher than in the placebo group (median [IQR], 84.8 [142] vs. 17.5 [37.6], p < .001). No adverse effects related to melatonin were observed in the study, and there were no significant differences in adverse effects between the melatonin and placebo groups. Although not statistically significant, the results of this randomized clinical trial proved that melatonin supplementation, as an add-on treatment, can improve spasm control rate in the treatment of IESS. For IESS children treated with ACTH, the addition of melatonin was found to improve sleep quality, shorten sleep onset latency, and increase blood melatonin levels. Moreover, it was observed to be a safe treatment option.
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Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials.
Lei, L, Hui, S, Chen, Y, Yan, H, Yang, J, Tong, S
Nutrition journal. 2024;(1):32
Abstract
BACKGROUND Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting outcomes concerning the correlation between soy isoflavone consumption and blood pressure levels. Consequently, a comprehensive meta-analysis of all eligible randomized controlled trials (RCTs) was conducted to explore the influence of soy isoflavones on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. METHODS A thorough search of PubMed, Embase, and the Cochrane Library for relevant literature up to April 30, 2023 was conducted. RCTs involving adults that compared soy isoflavone supplementation with a placebo (the same matrix devoid of soy isoflavone) were included. The combined effect size was presented as the weighted mean difference (WMD) along with 95% confidence interval (CI), employing a fixed-effects model. RESULTS Our meta-analysis included a total of 24 studies involving 1945 participants. The results revealed a significant reduction in both SBP and DBP with soy isoflavone supplementation. Subgroup analyses suggested more pronounced reductions in SBP and DBP for interventions lasting ≥6 months, in individuals receiving mixed-type soy isoflavone, and among patients with metabolic syndrome or prehypertension. However, we did not detect significant nonlinear associations between supplementation dosage and intervention duration concerning both SBP and DBP. The overall quality of evidence was deemed moderate. CONCLUSIONS The current meta-analysis revealed that supplementation with soy isoflavones alone effectively reduces blood pressure. Additional high-quality studies are required to investigate the efficacy of blood pressure reduction through supplementation with an optimal quantity and proportion of soy isoflavone.
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Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.
Guo, W, Zhao, L, Huang, W, Chen, J, Zhong, T, Yan, S, Hu, W, Zeng, F, Peng, C, Yan, H
Cardiovascular diabetology. 2024;(1):118
Abstract
BACKGROUND Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.
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Activating plant immunity: the hidden dance of intracellular Ca2+ stores.
Wang, Q, Cang, X, Yan, H, Zhang, Z, Li, W, He, J, Zhang, M, Lou, L, Wang, R, Chang, M
The New phytologist. 2024
Abstract
Calcium ion (Ca2+) serves as a versatile and conserved second messenger in orchestrating immune responses. In plants, plasma membrane-localized Ca2+-permeable channels can be activated to induce Ca2+ influx from extracellular space to cytosol upon pathogen infection. Notably, different immune elicitors can induce dynamic Ca2+ signatures in the cytosol. During pattern-triggered immunity, there is a rapid and transient increase in cytosolic Ca2+, whereas in effector-triggered immunity, the elevation of cytosolic Ca2+ is strong and sustained. Numerous Ca2+ sensors are localized in the cytosol or different intracellular organelles, which are responsible for detecting and converting Ca2+ signals. In fact, Ca2+ signaling coordinated by cytosol and subcellular compartments plays a crucial role in activating plant immune responses. However, the complete Ca2+ signaling network in plant cells is still largely ambiguous. This review offers a comprehensive insight into the collaborative role of intracellular Ca2+ stores in shaping the Ca2+ signaling network during plant immunity, and several intriguing questions for future research are highlighted.
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The Role of Total White Blood Cell Count in Antipsychotic Treatment for Patients with Schizophrenia.
Zhang, Y, Tao, S, Coid, J, Wei, W, Wang, Q, Yue, W, Yan, H, Tan, L, Chen, Q, Yang, G, et al
Current neuropharmacology. 2024;(1):159-167
Abstract
BACKGROUND Total white blood cell count (TWBCc), an index of chronic and low-grade inflammation, is associated with clinical symptoms and metabolic alterations in patients with schizophrenia. The effect of antipsychotics on TWBCc, predictive values of TWBCc for drug response, and role of metabolic alterations require further study. METHODS Patients with schizophrenia were randomized to monotherapy with risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perphenazine or haloperidol in a 6-week pharmacological trial. We repeatedly measured clinical symptoms, TWBCc, and metabolic measures (body mass index, blood pressure, waist circumference, fasting blood lipids and glucose). We used mixed-effect linear regression models to test whether TWBCc can predict drug response. Mediation analysis to investigate metabolic alteration effects on drug response. RESULTS At baseline, TWBCc was higher among patients previously medicated. After treatment with risperidone, olanzapine, quetiapine, perphenazine, and haloperidol, TWBCc decreased significantly (p < 0.05). Lower baseline TWBCc predicted greater reductions in Positive and Negative Syndrome Scale (PANSS) total and negative scores over time (p < 0.05). We found significant mediation of TWBCc for effects of waist circumference, fasting low-density lipoprotein cholesterol, and glucose on reductions in PANSS total scores and PANSS negative subscale scores (p < 0.05). CONCLUSION TWBCc is affected by certain antipsychotics among patients with schizophrenia, with decreases observed following short-term, but increases following long-term treatment. TWBCc is predictive of drug response, with lower TWBCc predicting better responses to antipsychotics. It also mediates the effects of certain metabolic measures on improvement of negative symptoms. This indicates that the metabolic state may affect clinical manifestations through inflammation.
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Effects of individualized dietary counseling on nutritional status and quality of life in post-discharge patients after surgery for gastric cancer: A randomized clinical trial.
Yan, H, He, F, Wei, J, Zhang, Q, Guo, C, Ni, J, Yang, F, Chen, Y
Frontiers in oncology. 2023;:1058187
Abstract
BACKGROUND Currently, the supporting evidence for dietary counseling is insufficient. The aim of this study is to evaluate the impact of individualized dietary counseling on nutritional outcomes and quality of life (QOL) in patients undergoing surgery for gastric cancer. METHODS This study was a prospective, single-center, randomized controlled trial. The patients after surgery for gastric cancer were randomly assigned (1:1) to the intervention group and the control group. In the intervention group, patients receive individualized dietary counseling based on individual calorie needs and symptom assessment at 24 h before discharge, 14, 21, 30, and 60 days postoperatively. Patients in the control group received routine dietary counseling. The primary endpoint was body mass index (BMI) loss at 30, 60, and 90 days after surgery; the secondary endpoints were calorie and protein intake at 30 and 60 days after surgery, blood parameters, the 90-day readmission rate, and QOL at 90 days after surgery. RESULTS One hundred thirty patients were enrolled; 67 patients were assigned to the intervention group and 63 patients to the control group. Compared with the control group, patients in the intervention group were significantly less BMI loss at 30 days (-0.84 ± 0.65 vs. -1.29 ± 0.83), 60 days (-1.29 ± 0.92 vs. -1.77 ± 1.13), and 90 days (-1.37 ± 1.05 vs. -1.92 ± 1.66) after surgery (all P< 0.05). Subgroups analysis by surgery type showed that the intervention could significantly reduce BMI loss in patients undergoing total and proximal gastrectomy at 30 days (-0.75 ± 0.47 vs. -1.55 ± 1.10), 60 days (-1.59 ± 1.02 vs. -2.55 ± 1.16), and 90 days (-1.44 ± 1.19 vs. -3.26 ± 1.46) after surgery (all P< 0.05). At 60 days after surgery, calorie goals were reached in 35 patients (77.8%) in the intervention group and 14 patients (40.0%) in the control group (P = 0.001), and protein goals were reached in 40 patients (88.9%) in the intervention group and 17 patients (48.6%) in the control group (P< 0.001). Regarding the QOL at 90 days after surgery, the patients in the intervention group had a significantly lower level of fatigue, shortness of breath and stomach pain, better physical function, and cognitive function (P< 0.05). CONCLUSIONS Post-discharge individualized dietary counseling is an effective intervention to reduce post-gastrectomy patient weight loss and to elevate calorie intake, protein intake, and QOL.
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The Interactions between Maternal Iron Supplementation and Iron Metabolism-Related Genetic Polymorphisms on Birth Outcomes: A Prospective Study in Chinese.
Liu, D, Cheng, Y, Qu, P, Zhao, D, Li, S, Zeng, L, Zhu, Z, Qi, Q, Mi, B, Zhang, B, et al
The Journal of nutrition. 2023;(8):2442-2452
Abstract
BACKGROUND The effect of iron supplementation during pregnancy on birth outcomes may vary with maternal genetic background and needs more investigation. OBJECTIVES This prospective study aimed to evaluate the interactions between maternal iron supplementation and iron metabolism-related genetic polymorphisms on birth outcomes. METHODS This was a substudy from a community-based randomized control trial conducted in Northwest China, which included 860 women from the 2 micronutrient supplementation groups (folic acid [FA] and FA + iron group). Maternal peripheral blood, sociodemographic and health-related information, and neonatal birth outcomes were collected. Six single nucleotide polymorphisms in iron metabolism-related genes were genotyped. The alleles associated with decreased iron/hemoglobin status were used as the effect alleles. The genetic risk score (GRS) that reflected the genetic risk of low iron/hemoglobin status was estimated using the unweighted and weighted methods. Generalized estimating equations with small-sample corrections were applied to evaluate the interactions between iron supplementation and SNPs/GRS on birth outcomes. RESULTS There were significant interactions between maternal iron supplementation and rs7385804 (P = 0.009), rs149411 (P = 0.035), rs4820268 (P = 0.031), the unweighted GRS (P = 0.018), and the weighted GRS (P = 0.009) on birth weight. Compared with FA supplementation only, FA + iron supplementation significantly increased birth weight among women with more effect alleles in rs7385804 (β: 88.8 g, 95% CI: 9.2, 168.3) and the GRSs (the highest unweighted GRS, β: 135.5 g, 95% CI: 7.7, 263.4; the highest weighted GRS, β: 145.9 g, 95% CI: 43.4, 248.5); it had a trend of decreasing birth weight and increasing low birth weight risk among women with fewer effect alleles. CONCLUSIONS In our population, maternal genetic background related to iron metabolism plays a significant role in determining the efficacy of iron supplementation. Routine iron supplementation could be more beneficial to fetal weight growth among mothers with higher genetic risk for low iron/hemoglobin status.
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Antibacterial and fluorescent clear aligner attachment resin modified with chlorhexidine loaded mesoporous silica nanoparticles and zinc oxide quantum dots.
Cao, L, Yan, J, Luo, T, Yan, H, Hua, F, He, H
Journal of the mechanical behavior of biomedical materials. 2023;:105817
Abstract
OBJECTIVES To develop an antibacterial and fluorescent clear aligner attachment resin via the incorporation of chlorhexidine loaded pore-expanded mesoporous silica nanoparticles (CHX@pMSN) and amino-silane functionalized zinc oxide quantum dots (aZnOQDs), and to evaluate its antibacterial activity, fluorescence capability, esthetic properties, mechanical performance and biocompatibility. METHODS CHX@pMSN and aZnOQDs were incorporated into the commercial resin composites (Filtek Z350 XT, 3M) at different mass fractions, control group: Filtek; fluorescent attachment resin (FAR): Filtek + 3 wt% aZnOQDs; antibacterial and fluorescent attachment resin (AFAR)-1: Filtek + 3 wt% aZnOQDs + 1 wt% CHX@pMSN; AFAR-2: Filtek + 3 wt% aZnOQDs + 3 wt% CHX@pMSN; AFAR-3: Filtek + 3 wt% aZnOQDs + 5 wt% CHX@pMSN. CHX release, antibacterial activity, fluorescence capability, color change, stain resistance, degree of conversion, depth of cure, polymerization shrinkage, water sorption and solubility, softening in solvent, flexural strength, flexural modulus, shear bond strength, and cytotoxicity were evaluated comprehensively. RESULTS CHX could be continuously released from the AFAR groups for up to 30 days. CFU, MTT, lactic acid production, SEM and CLSM evaluation showed AFAR-2 and AFAR-3 could effectively inhibit S. mutans biofilms even after 1-month aging. Only AFAR-3 showed clinically perceptible color change and all the experimental groups were not more susceptible to staining. AFAR-1 and AFAR-2 could suppress polymerization shrinkage and enhance the resistance to degradation without compromising other properties, including degree of conversion, water sorption and solubility, flexural strength, flexural modulus, and shear bond strength. Depth of cure of all the four experimental groups was significantly decreased (p < 0.05) but still within the ISO standard. CCK-8 assay and live/dead cell staining denied the cytotoxicity of experimental resins. Fluorescence intensity tests showed that FAR and AFAR-2 could emit strong yellowish fluorescence under the excitation of ultraviolet for up to six months. CONCLUSIONS AFRA-2 possessed long-term antibiofilm activity, strong fluorescence capability and satisfying biocompatibility without compromising esthetic and mechanical properties. This study proposed a new strategy for reducing bacteria accumulation around the attachment, which is also promising in helping orthodontists to remove the attachment thoroughly and precisely.
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Ferroptosis in colorectal cancer: a future target?
Yan, H, Talty, R, Aladelokun, O, Bosenberg, M, Johnson, CH
British journal of cancer. 2023;(8):1439-1451
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Abstract
Colorectal cancer (CRC) is the third leading cause of cancer deaths worldwide and is characterised by frequently mutated genes, such as APC, TP53, KRAS and BRAF. The current treatment options of chemotherapy, radiation therapy and surgery are met with challenges such as cancer recurrence, drug resistance, and overt toxicity. CRC therapies exert their efficacy against cancer cells by activating biological pathways that contribute to various forms of regulated cell death (RCD). In 2012, ferroptosis was discovered as an iron-dependent and lipid peroxide-driven form of RCD. Recent studies suggest that therapies which target ferroptosis are promising treatment strategies for CRC. However, a greater understanding of the mechanisms of ferroptosis initiation, propagation, and resistance in CRC is needed. This review provides an overview of recent research in ferroptosis and its potential role as a therapeutic target in CRC. We also propose future research directions that could help to enhance our understanding of ferroptosis in CRC.