-
1.
Roxadustat and Oral Iron Absorption in Chinese Patients with Anemia of Chronic Kidney Disease: A Randomized, Open-Label, Phase 4 Study (ALTAI).
Wu, H, Cheng, H, Wang, C, Yao, L, Qin, S, Zuo, L, Hu, Z, Zhang, C, Wu, Y, Hofherr, A, et al
Advances in therapy. 2024;(3):1168-1183
-
-
Free full text
-
Abstract
INTRODUCTION Anemia of chronic kidney disease (CKD) has a high incidence and is associated with many disease conditions. Iron dysmetabolism is an important contributor to anemia in CKD patients. METHODS ALTAI, a randomized, active-controlled, phase 4 trial, investigated the efficacy of roxadustat versus recombinant human erythropoietin (rHuEPO) on gastrointestinal iron absorption in patients with anemia of CKD (stage 4/5). The primary endpoint was change from baseline to day 15 in gastrointestinal iron absorption (serum iron area under the concentration-time curve; AUC0-3h) following single-dose oral iron. RESULTS Twenty-five patients with a mean age of 55.1 years were randomized 1:1 to roxadustat (n = 13) or rHuEPO (n = 12). Baseline iron profiles were similar between treatment groups. Change from baseline to day 15 in serum iron AUC0-3h was not statistically significantly different between the roxadustat and rHuEPO groups. Mean (SD) change from baseline in serum iron AUC0-3h was 11.3 (28.2) g × 3 h/dl in the roxadustat group and - 0.3 (9.7) g × 3 h/dl in the rHuEPO group. Roxadustat treatment was associated with decreased hepcidin and also increased transferrin, soluble transferrin receptor, and total iron-binding capacity (TIBC), with nominal significance. The proportion of patients experiencing one or more adverse events was 38.5% when treated with roxadustat and 16.7% with rHuEPO. CONCLUSIONS The study showed no significant difference between roxadustat and rHuEPO in iron absorption but was underpowered because of recruitment challenges. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT04655027.
-
2.
Effects and plasma proteomic analysis of GLP-1RA versus CPA/EE, in combination with metformin, on overweight PCOS women: a randomized controlled trial.
Liao, M, Li, X, Zhang, H, Zhou, L, Shi, L, Li, W, Shen, R, Peng, G, Zhao, H, Shao, J, et al
Endocrine. 2024;(1):227-241
-
-
Free full text
-
Abstract
PURPOSE Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS. METHODS In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-μg ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2-1.8 mg/day) +Met (1500 mg/day) for 12 weeks. The clinical effectiveness and adverse effects were evaluated, followed by plasma proteomic analysis and verification of critical biomarkers by ELISA. RESULTS Eighty(80%) patients completed the study. Both interventions improved menstrual cycle, polycystic ovaries, LH(luteinizing hormone) and HbA1c(hemoglobin A1c) levels after the 12-week treatment. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI (Body Mass Index), and waist circumference, FBG(fasting blood glucose), AUCI(area under curve of insulin),TC (Total Cholesterol), IL-6(Interleukin-6) and improving insulin sensitivity, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in improving hyperandrogenemia, including T(total testosterone), LH, LH/FSH(Luteinizing hormone/follicle-stimulating hormone), SHBG(sex hormone-binding globulin) and FAI (free androgen index). By contract, GLP-1RA+Met group only improved LH. Plasma proteomic analysis revealed that the interventions altered proteins involved in reactive oxygen species detoxification (PRDX6, GSTO1, GSTP1, GSTM2), platelet degranulation (FN1), and the immune response (SERPINB9). CONCLUSIONS Both CPA/EE+Met and GLP-1RA + Met treatment improved reproductive functions in overweight PCOS women. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI, and waist, and improving metabolism, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in reducing hyperandrogenemia. The novel plasma biomarkers PRDX6, FN1, and SERPINB9, might be indicators and targets for PCOS treatment. TRIAL REGISTRATION CLINICALTIALS. GOV TRIAL NO NCT03151005. Registered 12 May, 2017, https://clinicaltrials.gov/ct2/show/NCT03151005 .
-
3.
Does an antihypertensive diet cost more? Analysis from the Chinese Heart-Healthy diet trial.
Guo, Y, Su, D, Chen, H, Ding, Y, Zhang, S, Sun, H, Chen, D, Yin, W, Li, X, Zeng, G
Public health nutrition. 2024;(1):e73
-
-
Free full text
-
Abstract
OBJECTIVE To determine whether the Chinese heart-healthy diet (Sichuan cuisine version) (CHH diet-SC) was more expensive than the conventional Sichuan diet and explore the food groups and nutrients that mainly affected the cost of CHH diet-SC. DESIGN Cost analysis of 4-week intervention diets in the Sichuan center representing southwestern China in the CHH diet study. SETTING A multicentre, parallel-group, single-blind, randomised feeding trial evaluating the efficacy of lowering blood pressure with the cuisine-based CHH diet. PARTICIPANTS Totally, fifty-three participants with hypertension aged 25-75 years in the Sichuan center were randomised into the control group (n 26) or the CHH diet-SC group (n 27). RESULTS The CHH diet-SC was more expensive than the control diet (¥27·87 ± 2·41 v. ¥25·18 ± 2·79 equals $3·90 ± 0·34 v. $3·52 ± 0·39, P < 0·001), and the incremental cost-effectiveness ratio for a 1-mm Hg systolic blood pressure reduction was ¥9·12 ($1·28). Intakes and the cost of seafood, dairy products, fruits, soybeans and nuts, whole grains and mixed beans were higher for the CHH diet-SC than for the control diet (P < 0·001). Intakes of vitamin B1, vitamin B6, vitamin C, Mg and phosphorus were positively correlated with the cost (P < 0·05). CONCLUSIONS The CHH diet-SC costs more than the conventional Sichuan diet, partly due to the high cost of specific food groups. Positive correlations between the intakes of vitamin B1, vitamin B6, vitamin C, Mg, phosphorus and the dietary cost could be a direction to adjust the composition within the food groups to reduce the cost of the CHH diet-SC.
-
4.
[Parecoxib sodium down-regulates CXCL8-CXCR1/2 to improve inflammatory microenvironment and promote patient recovery following laparoscopic radical resection of rectal cancer].
Wu, R, Liu, R, Zhang, Y, Li, X
Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 2024;(2):363-369
Abstract
OBJECTIVE To study the effect of parecoxib sodium on tumor microenvironment in patients undergoing laparoscopic radical resection of rectal cancer. METHODS Sixty patients undergoing laparoscopic surgery for radical rectal cancer resection were randomized into test group and control group (n=30). The patients in test control group received intravenous injections of 40 mg parecoxib sodium at the time of anesthesia induction, immediately after and at 12 h after the surgery, and those in the control group were injected with an equal volume of physiological saline at the same time points. Plasma levels of IL-6, TNF-α, and CXCL8 of the patients were measured using ELISA, and expressions of CXCL8, CXCR1, and CXCR2 in the peripheral blood mononuclear cells (PBMCs) were detected with Western blotting. Postoperative VAS scores and gastrointestinal reactions and disease regression at 6 months after the operation were recorded. RESULTS Compared with the control patients, the patients in the test group showed significantly reduced plasma levels of IL-6, TNF-α, and CXCL8 (P < 0.05) and milder elevations of CXCL8, CXCR1, and CXCR2 proteins in PBMCs (P < 0.05) with significantly lower VAS scores at 12 h and 24 h after the operation (P < 0.05) and lower postoperative incidence of adverse gastrointestinal reactions (P < 0.05). At 6 months after the operation, the number of patients with metastasis or tumor recurrence was significantly smaller in the test group than in the control group (P>0.05). CONCLUSION Parecoxib sodium can improve the inflammatory microenvironment to promote patient recovery after laparoscopic radical resection of rectal cancer possibly through a mechanism that down-regulates CXCL8-CXCR1/2 expressions in the PBMCs.
-
5.
DNA Methylation Near CPT1A and Changes in Triglyceride-rich Lipoproteins in Response to Weight-loss Diet Interventions.
Li, X, Shao, X, Xue, Q, Kou, M, Champagne, CM, Koseva, BS, Heianza, Y, Grundberg, E, Bazzano, LA, Bray, GA, et al
The Journal of clinical endocrinology and metabolism. 2023;(8):e542-e549
-
-
Free full text
-
Abstract
CONTEXT Carnitine palmitoyltransferase-1A, encoded by the CPT1A gene, plays a key role in the oxidation of long-chain fatty acids in the mitochondria and may be important in triglyceride metabolism. Previous work has shown that high fat intake was negatively associated with CPT1A methylation and positively associated with CPT1A expression. OBJECTIVE We aim to investigate the association of DNA methylation (DNAm) at the CPT1A gene with reductions in triglycerides and triglyceride-rich lipoproteins (TRLs) in response to weight-loss diet interventions. METHODS The current study included 538 White participants, who were randomly assigned to 1 of 4 diets varying in macronutrient components. We defined the regional DNAm at CPT1A as the average methylation level over CpGs within 500 bp of the 3 triglyceride-related DNAm sites. RESULTS Dietary fat intake significantly modified the association between baseline DNAm at CPT1A and 2-year changes in total plasma triglycerides, independent of concurrent weight loss. Among participants assigned to a low-fat diet, a higher regional DNAm level at CPT1A was associated with a greater reduction in total plasma triglycerides at 2 years (P = .01), compared with those assigned to a high-fat diet (P = .64) (P interaction = .018). Further investigation on lipids and apolipoproteins in very low-density lipoprotein (VLDL) revealed similar interaction patterns for 2-year changes in VLDL-triglycerides, VLDL-cholesterol, and VLDL-apolipoprotein B (P interaction = .009, .002, and .016, respectively), but not for VLDL-apoC-III (P interaction = .36). CONCLUSION Participants with a higher regional DNAm level at CPT1A benefit more in long-term improvement in triglycerides, particularly in the TRLs and related apolipoproteins when consuming a low-fat weight-loss diet.
-
6.
The Effectiveness of an eHealth Family-Based Intervention Program in Patients With Uncontrolled Type 2 Diabetes Mellitus (T2DM) in the Community Via WeChat: Randomized Controlled Trial.
Feng, Y, Zhao, Y, Mao, L, Gu, M, Yuan, H, Lu, J, Zhang, Q, Zhao, Q, Li, X
JMIR mHealth and uHealth. 2023;:e40420
Abstract
BACKGROUND Intervention based on family support and risk perception can enhance type 2 diabetes mellitus (T2DM) patients' self-care activities. In addition, eHealth education is considered to improve family members' support for patients with T2DM. However, there is little evidence from rigorously designed studies on the effectiveness of an intervention combining these approaches. OBJECTIVE This randomized controlled trial (RCT) aimed to assess the effectiveness of an eHealth family-based health education intervention for patients with T2DM to improve their glucose control, risk perception, and self-care behaviors. METHODS This single-center, 2-parallel-group RCT was conducted between 2019 and 2020. Overall, 228 patients were recruited from Jiading District, Shanghai, and randomly divided into intervention and control groups. The intervention group received an eHealth family intervention based on community management via WeChat, whereas the control group received usual care. The primary outcome was the glycated hemoglobin (HbA1c) level of the patients with T2DM, and the secondary outcomes were self-management behavior (general and specific diet, exercise, blood sugar testing, foot care, and smoking), risk perception (risk knowledge, personal control, worry, optimism bias, and personal risk), and family support (supportive and nonsupportive behaviors). A 2-tailed paired-sample t test was used to compare the participants at baseline and follow-up within the control and intervention groups. An analysis of covariance was used to measure the intervention effect. RESULTS In total, 225 patients with T2DM were followed up for 1 year. After intervention, they had significantly lower HbA1c values (β=-.69, 95% CI -0.99 to -0.39; P<.001). They also had improved general diet (β=.60, 95% CI 0.20 to 1.00; P=.003), special diet (β=.71, 95% CI 0.34 to 1.09; P<.001), blood sugar testing (β=.50, 95% CI 0.02 to 0.98; P=.04), foot care (β=1.82, 95% CI 1.23 to 2.42; P<.001), risk knowledge (β=.89, 95% CI 0.55 to 1.24; P<.001), personal control (β=.22, 95% CI 0.12 to 0.32; P<.001), worry (β=.24, 95% CI 0.10 to 0.39; P=.001), optimism bias (β=.26, 95% CI 0.09 to 0.43; P=.003), and supportive behaviors (β=5.52, 95% CI 4.03 to 7.01; P<.001). CONCLUSIONS The eHealth family-based intervention improved glucose control and self-care activities among patients with T2DM by aiding the implementation of interventions to improve T2DM risk perceptions among family members. The intervention is generalizable for patients with T2DM using health management systems in community health centers. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR1900020736; https://www.chictr.org.cn/showprojen.aspx?proj=31214.
-
7.
Probiotics intervention in preventing conversion of impaired glucose tolerance to diabetes: The PPDP follow-on study.
Yan, Q, Hu, W, Tian, Y, Li, X, Yu, Y, Li, X, Feng, B
Frontiers in endocrinology. 2023;14:1113611
-
-
-
Free full text
Plain language summary
Compared with normal glucose tolerance, people with prediabetes, especially impaired glucose tolerance (IGT), have a higher risk of developing type 2 diabetes mellitus (T2DM). Early intervention can significantly reduce the probability of developing T2DM in the IGT population. The aim of this study was to observe the effect of early probiotic intervention on the conversion of T2DM after 6 years. This study was a follow-on study of the Probiotics Prevention Diabetes Program (PPDP) Study. A total of 39 non-T2DM patients agreed to continue with the follow up of glucose metabolism for the following 4 years. Results showed that supplementation with active probiotics of Bifidobacterium, Lactobacillus acidophilus and Enterococcus faecalis is safe, although it does not reduce the risk of IGT conversion to diabetes mellitus. Authors conclude that more clinical and laboratory studies using large samples and long-term observation are needed to explore the effects of different probiotic strains on IGT.
Abstract
OBJECTIVES The purpose of this study was to assess the incidence of type 2 diabetes mellitus (T2DM) after 6 years in patients with IGT who received early probiotic intervention in the Probiotics Prevention Diabetes Program (PPDP) trial. METHODS 77 patients with IGT in the PPDP trial were randomized to either probiotic or placebo. After the completion of the trial, 39 non-T2DM patients were invited to follow up glucose metabolism after the next 4 years. The incidence of T2DM in each group was assessed using Kaplan-Meier analysis. The 16S rDNA sequencing technology was used to analyze gut microbiota's structural composition and abundance changes between the groups. RESULTS The cumulative incidence of T2DM was 59.1% with probiotic treatment versus 54.5% with placebo within 6 years, there was no significant difference in the risk of developing T2DM between the two groups (P=0.674). CONCLUSIONS Supplemental probiotic therapy does not reduce the risk of IGT conversion to T2DM. CLINICAL TRIAL REGISTRATION https://www.chictr.org.cn/showproj.aspx?proj=5543, identifier ChiCTR-TRC-13004024.
-
8.
Effect of synbiotic supplementation on immune parameters and gut microbiota in healthy adults: a double-blind randomized controlled trial.
Li, X, Hu, S, Yin, J, Peng, X, King, L, Li, L, Xu, Z, Zhou, L, Peng, Z, Ze, X, et al
Gut microbes. 2023;15(2):2247025
-
-
-
Free full text
-
Plain language summary
The gut microbiota is involved in regulating immunity and synbiotics, that is combinations of pro- and prebiotics, may therefore modulate immunity via the gut microbiota. The aim of this randomised, double-blind, placebo-controlled trial was to evaluate the immune-modulatory effects of a synbiotic supplement (containing Bifidobacterium lactis HN019, Lactobacillus rhamnosus HN001 and fructo-oligosaccharide) in healthy adults. Outcome measures included C-reactive protein (CRP, an inflammatory marker), various pro- and anti-inflammatory cytokines, stool and salivary secretory IgA (sIgA), leukocytes, microbial stool analysis and occurrence, duration, and severity of upper respiratory tract infections (URTI). Compared to the control group, a significant reduction in the inflammatory markers CRP and interferon-gamma and an increase in the anti-inflammatory interleukin-10 and stool sIgA were observed in the supplementation group. There were no differences in types of leukocytes or URTIs between groups. Significant favourable changes in microbiome analysis were observed in the supplemented group which correlated with the observed improvements in inflammatory markers. These changes were dependent on the baseline composition of the microbiome. No adverse events were reported. The authors conclude that the data show that synbiotics are of benefit to healthy adults and support the concept of personalised supplementation.
Abstract
Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.
-
9.
Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study.
Wang, C, Sun, W, Dalbeth, N, Wang, Z, Wang, X, Ji, X, Xue, X, Han, L, Cui, L, Li, X, et al
Arthritis research & therapy. 2023;(1):164
Abstract
BACKGROUND Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied. OBJECTIVES This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate. METHODS A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 μmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints. RESULTS Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups. CONCLUSION The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT. TRIAL REGISTRATION This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749.
-
10.
Establishment and validation of a prognostic nomogram for long-term low vision after diabetic vitrectomy.
Guo, H, Wang, Z, Nie, Z, Zhang, X, Wang, K, Duan, N, Bai, S, Li, W, Li, X, Hu, B
Frontiers in endocrinology. 2023;:1196335
Abstract
PURPOSE We aimed to evaluate the risk factors and develop a prognostic nomogram of long-term low vision after diabetic vitrectomy. METHODS This retrospective study included 186 patients (250 eyes) that underwent primary vitrectomy for proliferative diabetic retinopathy with a minimum follow-up period of one year. Patients were assigned to the training cohort (200 eyes) or validation cohort (50 eyes) at a 4:1 ratio randomly. Based on a cutoff value of 0.3 in best-corrected visual acuity (BCVA) measurement, the training cohort was separated into groups with or without low vision. Univariate and multivariate logistic regression analyses were performed on preoperative systemic and ocular characteristics to develop a risk prediction model and nomogram. The calibration curve and the area under the receiver operating characteristic curves (AUC) were used to evaluate the calibration and discrimination of the model. The nomogram was internally validated using the bootstrapping method, and it was further verified in an external cohort. RESULTS Four independent risk factors were selected by stepwise forward regression, including tractional retinal detachment (β=1.443, OR=4.235, P<0.001), symptom duration ≥6 months (β=0.954, OR=2.595, P=0.004), preoperative BCVA measurement (β=0.540, OR=1.716, P=0.033), and hypertension (β=0.645, OR=1.905, P=0.044). AUC values of 0.764 (95% CI: 0.699-0.829) in the training cohort and 0.755 (95% CI: 0.619-0.891) in the validation cohort indicated the good predictive ability of the model. CONCLUSION The prognostic nomogram established in this study is useful for predicting long-term low vision after diabetic vitrectomy.