Jin Hua Chen

The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial.

Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 10(9) cfu Bifobacterium bifidum A218, 10(9) cfu Bifidobacterium catenulatum A302, 10(9) cfu Bifidobacterium longum A101, and 10(9) cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.

Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis

Background Some oral probiotics have been shown to prevent necrotizing enterocolitis (NEC) and decrease mortality effectively in preterm very low birth weight (PVLBW) infants. However, it is unclear whether a single probiotic or a mixture of probiotics is most effective for the prevention of NEC. Objective A meta-analysis was conducted by reviewing the most up to date literature to investigate whether multiple strains probiotics are more effective than a single strain in reducing NEC and death in PVLBW infants. Data sources Relevant studies were identified by searches of the MEDLINE, EMBASE, and Cochrane CENTRAL databases, from 2001 to 2016. Data extraction and synthesis The inclusion criteria were randomized controlled trials of any enteral probiotic supplementation that was initiated within the first 7 days and continued for at least 14 days in preterm infants (≤ 34 weeks’ gestation) and/or those of a birth weight ≤1500 g. Results A total of 25 trials (n = 7345 infants) were eligible for inclusion in the meta-analysis using a fixed-effects model. Multiple strains probiotics were associated with a marked reduction in the incidence of NEC, with a pooled OR of 0.36 (95% CI, 0.24–0.53; P < .00001). Single strain probiotic using Lactobacillus species had a borderline effect in reducing NEC (OR of 0.60; 95% CI 0.36–1.0; P = .05), but not mortality. Multiple strains probiotics had a greater effectiveness in reducing mortality and were associated with a pooled OR of 0.58 (95% CI, 0.43–0.79; P = .0006). Trials using single strain of Bifidobacterium species and Saccharomyces boulardii did not reveal any beneficial effects in terms of reducing NEC or mortality. Conclusion This updated report found that multiple strains probiotics appear to be the most feasible and effective strategy for the prevention of NEC and reduction of mortality in PVLBW neonates. Further clinical trials should focus on which probiotic combinations are most effective.

Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan.

Kawasaki disease (KD) is an acute, inflammatory, and self-limited vasculitis affecting infants and young children. Coronary artery aneurysm (CAA) formation is the major complication of KD and the leading cause of acquired cardiovascular disease among children. To identify susceptible loci that might predispose patients with KD to CAA formation, a genome-wide association screen was performed in a Taiwanese KD cohort. Patients with both KD and CAA had longer fever duration and delayed intravenous immunoglobulin treatment time. After adjusting for these factors, 100 susceptibility loci were identified. Four genes were identified from a single cluster of 35 using the Ingenuity Pathway Analysis (IPA) Knowledge Base. Silencing KCNQ5, PLCB1, PLCB4, and PLCL1 inhibited the effect of lipopolysaccharide-induced endothelial cell inflammation with varying degrees of proinflammatory cytokine expression. PLCB1 showed the most significant inhibition. Endothelial cell inflammation was also inhibited by using a phospholipase C (PLC) inhibitor. The single nucleotide polymorphism rs6140791 was identified between PLCB4 and PLCB1. Plasma PLC levels were higher in patients with KD and CC+CG rs6140791genotypes, and these genotypes were more prevalent in patients with KD who also had CAA. Our results suggest that polymorphism of the PLCB4/B1 genes might be involved in the CAA pathogenesis of KD.

Association between GRIN3A Gene Polymorphism in Kawasaki Disease and Coronary Artery Aneurysms in Taiwanese Children

Kawasaki disease (KD) is pediatric systemic vasculitis with the classic complication of coronary artery aneurysm (CAA). It is the leading cause of acquired cardiovascular diseases in children. Some severe cases present with multi-organ involvement or neurological dysfunction. To identify the role of the glutamate receptor, ionotropic, N-methyl-d-aspartate 3A (GRIN3A) in KD, we investigated genetic variations in GRIN3A in a Taiwanese cohort of 262 KD patients (76 with and 186 without CAA complications). We used univariate and multivariate regression analyses to identify the associations between clinical characteristics and GRIN3A genetic variations in KD. According to univariate regression analysis, CAA formation in KD was significantly associated with fever duration (p < 0.0001), first Intravenous immunoglobulin (IVIG) used (days after day one of fever) (p < 0.0001), and the GRIN3A (rs7849782) genetic variant (p < 0.001). KD patients with GG+GC genotype showed a lower rate of developing CAA (GG+GC genotype: odds ratio = 0.26; 95% CI = 0.14–0.46). Significant associations were identified between KD with CAA complication and the GRIN3A (rs7849782) genetic variant by using multivariate regression analysis. Specifically, significant correlations were observed between KD with CAA complications and the presence of GG+GC genotypes for the GRIN3A rs7849782 single-nucleotide polymorphism (full model: odds ratio = 0.25; 95% CI = 0.14–0.46). Our results suggest that a polymorphism of the GRIN3A gene may play a role in KD pathogenesis.

Chinese Herbal Medicine Treatment Improves the Overall Survival Rate of Individuals with Hypertension among Type 2 Diabetes Patients and Modulates In Vitro Smooth Muscle Cell Contractility

Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients.

Gustatory changes in patients with chronic otitis media, before and after middle-ear surgery.

OBJECTIVE We investigated gustatory changes in patients with chronic otitis media, before and after middle-ear surgery. METHODS This prospective study included 38 patients with unilateral chronic otitis media. We used taste testing solutions to evaluate each patients taste function. Intra-operative assessments of the chorda tympani nerve were also compared and analysed. RESULTS Patients with chronic otitis media had significantly worse ipsilateral perception of sour, bitter and salty tastes. In patients with good intra-operative preservation of the chorda tympani nerve, there was significant improvement in gustatory function one month post-operatively, compared with the pre-operative baseline. In patients who sustained intra-operative chorda tympani nerve injury, one month post-operative gustatory function was the same as the pre-operative baseline. CONCLUSION Middle-ear surgery for chronic otitis media not only treats the ear but also improves gustatory function in the majority of patients. In patients with intra-operative injury to the chorda tympani nerve, post-operative taste decline is only temporary.

Association of Promoter Genetic Variants in Interleukin-10 and Kawasaki Disease With Coronary Artery Aneurysms

Kawasaki disease (KD) is an acute, self‐limited vasculitis in infants and young children. Interleukin‐10 (IL‐10) is a potent cytokine that exerts pleiotropic effects on immunoregulation and inflammation. Elevated IL‐10 serum levels have been reported in the KD patients.

Coronary artery aneurysms occurrence risk analysis between Kawasaki disease and LRP1B gene in Taiwanese children

Background: Kawasaki disease (KD) is an acute and systemic vasculitis. Its complications in coronary artery aneurysms (CAA) make KD one of the leading causes of acquired cardiovascular diseases in childhood. Low density lipoprotein receptor-related protein 1B (LRP1B) is abundantly expressed in the medial layer of coronary arteries and involved in endothelium inflammations. Purpose: We aimed to identify the role of LRP1B in CAA formation during KD progression. Methods: we investigated genetic variations in LRP1B in a Taiwanese cohort of 258 KD patients (83 with CAA and 175 without CAA complications). We used univariate and multivariate regression analyses to identify the associations between LRP1B genetic variations and KD patients. Results: CAA formation in KD was significantly associated with the LRP1B (rs6707826) genetic variant (p = 0.007). By using multivariate regression analysis, significant correlations were observed between KD with CAA complications and the presence of the TT+TG genotypes for the LRP1B rs6707826 single-nucleotide polymorphism (full model: odds ratio = 2.82; 95% CI = 1.33–5.78). Conclusion: Our results suggest that genetic polymorphism of LRP1B gene may be used as a genetic marker for the diagnosis and prognosis of the CAA formation in KD and contribute to genetic profiling studies for personalized medicine.

Characteristics of Chinese herbal medicine usage in ischemic heart disease patients among type 2 diabetes and their protection against hydrogen peroxide-mediated apoptosis in H9C2 cardiomyoblasts

Evidence for long-term use of Chinese herbal medicine (CHM) as an adjuvant treatment in patients with type 2 diabetes (T2D) remains limited. This study aimed to assess the frequency of use, utilization patterns, and therapeutic effects of adjuvant CHM for ischemic heart disease (IHD) in patients with T2D in Taiwan. We identified 4620 IHD patients with T2D. After matching for age, gender, and insulin use, 988 subjects each were allocated to a CHM group and a non-CHM group. There were no differences in baseline characteristics except for comorbidities. The CHM group contained more cases with chronic obstructive pulmonary disease, hepatitis, ulcer disease, and hyperlipidemia. The cumulative survival probability was higher in CHM users than in matched non-CHM users aged 60 years or older (P < .0001, log rank test) regardless of gender (P = .0046 for men, P = .0010 for women, log rank test). Among the top 12 CHM combinations, Shu-Jing-Huo-Xue-Tang and Shao-Yao-Gan-Cao-Tang (13.6%) were the most common. This dual combination improved antiapoptotic activity in H2O2-exposed H9C2 cells by enhancing phosphorylation of glycogen synthase kinase-3β and p38 mitogen-activated protein kinase and could increase the survival of myocardial cells. Our study suggests that adjuvant CHM therapy may increase the survival probability and provides a comprehensive list for future investigations of the safety and efficacy of CHM for IHD patients with T2D.

Genetic variants of glutamate receptor gene family in Taiwanese Kawasaki disease children with coronary artery aneurysms

BackgroundPatients with Kawasaki disease (KD), a pediatric systemic vasculitis, may develop coronary artery aneurysm (CAA) as a complication. To investigate the role of glutamate receptors in KD and its CAA development, we performed genetic association studies.Methods and resultsWe examined the whole family of glutamate receptors by genetic association studies in a Taiwanese cohort of 262 KD patients. We identified glutamate receptor ionotropic, kainate 1 (GRIK1) as a novel susceptibility locus associated with CAA formation in KD. Statistically significant differences were noted for factors like fever duration, 1st Intravenous immunoglobulin (IVIG) used time (number of days after the first day of fever) and the GRIK1 (rs466013, rs425507, and rs38700) genetic variants. This significant association persisted even after using multivariate regression analysis (Full model: for rs466013: odds ratio =2.12; 95% CI =1.22-3.65; for rs425507: odds ratio =2.16; 95% CI =1.26-3.76; for rs388700: odds ratio =2.16; 95% CI =1.26-3.76).ConclusionsWe demonstrated that GRIK1 polymorphisms are associated CAA formation in KD, even when adjusted for fever duration and IVIG used time, and may also serve as a genetic marker for the CAA formation in KD.