Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight.

BACKGROUND: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. METHODS: Bile samples from 20 patients (10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by further bioinformatic analysis. RESULTS: Among the differentially-expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially-expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor (PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APOA-I and APOA-II, were confirmed using enzyme-linked immunosorbent assay. CONCLUSIONS: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.

Cyclosporine A-induced gingival overgrowth in renal transplant patients accompanied by epithelial-to-mesenchymal transition.

OBJECTIVE: To investigate the association between the prevalence of cyclosporin A-induced gingival overgrowth and the expression of the epithelial-to-mesenchymal transition factors in the gingival tissues of renal transplant patients. BACKGROUND: Gingival overgrowth (GO) is a frequent complication in organ transplant patients treated with the immunosuppressant cyclosporin A (CsA). The epithelial-to-mesenchymal transition (EMT) is considered a factor contributing to CsA-induced GO. However, current knowledge on this topic is sparse. METHODS: Sixty-three renal transplant patients were divided into two groups according to the occurrence of GO: those with gingival overgrowth (GO+ group) and those without gingival overgrowth (GO- group). Data on age, sex, and use of immunosuppressant and calcium channel blocker medications, serum creatinine values, peak concentrations of blood CsA, and gingival hyperplasia scores were recorded to identify clinically pathogenic factors. Gingival tissues from five patients with CsA-induced GO and five healthy subjects were selected for histomorphological observation with hematoxylin-eosin staining, Masson staining, and immunohistochemical staining. The mRNA expression of EMT factors was detected with reverse transcription-quantitative PCR. RESULTS: The use of CsA significantly increased the prevalence of GO in renal transplant patients. The expression of α-SMA, SMAD4, and TGM2 was upregulated and that of E-cadherin was downregulated in the gingival tissues of patients with CsA-induced GO compared with those of the corresponding controls. CONCLUSION: Treatment with CsA is closely related to the occurrence of GO in renal transplant patients and EMT plays an important role in CsA-induced gingival tissue hyperplasia.

µ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects.

Human genetic and pharmacological studies have demonstrated that voltage-gated sodium channels (VGSCs) are promising therapeutic targets for the treatment of pain. Spider venom contains many toxins that modulate the activity of VGSCs. To date, only 0.01% of such spider toxins has been explored, and thus there is a great potential for discovery of novel VGSC modulators as useful pharmacological tools or potential therapeutics. In the current study, we identified a novel peptide, µ-TRTX-Ca1a (Ca1a), in the venom of the tarantula Cyriopagopus albostriatus. This peptide consisted of 38 residues, including 6 cysteines, i.e. IFECSISCEIEKEGNGKKCKPKKCKGGWKCKFNICVKV. In HEK293T or ND7/23 cells expressing mammalian VGSCs, this peptide exhibited the strongest inhibitory activity on Nav1.7 (IC50 378 nM), followed by Nav1.6 (IC50 547 nM), Nav1.2 (IC50 728 nM), Nav1.3 (IC50 2.2 µM) and Nav1.4 (IC50 3.2 µM), and produced negligible inhibitory effect on Nav1.5, Nav1.8, and Nav1.9, even at high concentrations of up to 10 µM. Furthermore, this peptide did not significantly affect the activation and inactivation of Nav1.7. Using site-directed mutagenesis of Nav1.7 and Nav1.4, we revealed that its binding site was localized to the DIIS3-S4 linker region involving the D816 and E818 residues. In three different mouse models of pain, pretreatment with Cala (100, 200, 500 µg/kg) dose-dependently suppressed the nociceptive responses induced by formalin, acetic acid or heat. These results suggest that Ca1a is a novel neurotoxin against VGSCs and has a potential to be developed as a novel analgesic.

[The correlation of age with the risk of multiple organ dysfunction syndrome in the elderly patients with congestive heart failure and hypertension].

OBJECTIVE: To study the prediction value of age and congestive heart failure (CHF) for occurrence of multiple organ dysfunction syndrome elderly(MODSE) in old patients with hypertension. METHODS: Medical history of 19,996 cases (aged over 60 year) admitted to PLA General Hospital because of hypertension or developing hypertension during hospital stay from Jan 1993 to Dec 2008 were analyzed retrospectively. According to age the patients were divided into four groups: 60-69 year group; 70-79 year group; 80-89 year group; > or = 90 year older group. The incidence of CHF and the morbidity of MODSE induced by CHF at different ages and different boundary ages were investigated. RESULTS: 1. The incidence of MODSE in CHF cases was higher than that in the non-CHF cases (7.43% versus 3.05%, Chi(2) 195.15, P < 0.01), showing CHF were the important factor in happening of MODSE. 2. The incidence of CHF and the morbidity of MODSE were 10.60% versus 18.88% versus 30.11% versus 60.57%, P <0.05, P < 0.05 and 1.6 versus 7.0 versus 17.08 versus 25.47% , in 60-69 year group; 70-79 year group; 80-89 year group; > or =90 year older group, P < 0.05. Occurrence of CHF and that of MODSE were positively correlated with age (r = 0.696 - 0.987, P < 0.01). High risk population of MODSE induced by CHF were old patients with hypertension above 69 year old. CONCLUSION: The age is valuable for early prediction of MODSE induced by CHF in old patients with hypertension. The distinctly boundary age for the incidence of MODSE induced by CHF in old patients with hypertension is 69.

Association of common polymorphisms in the LRP6 gene with sporadic coronary artery disease in a Chinese population.

BACKGROUND: Genetic factors contribute to the development of coronary artery disease (CAD). Recently, a missense mutation in the low density lipoprotein receptor related protein 6 (LRP6) gene, encoding low density lipoprotein receptor related protein 6, has been implicated in an autosomal dominant form of early-onset CAD. The aim of this study was to determine whether the common variants in LRP6 are associated with sporadic CAD in Chinese. METHODS: A total of 766 CAD patients and 806 healthy controls were included in this study. The presence of angiographic CAD was determined by coronary angiographic analysis. Six signal nucleotide polymorphisms (SNPs) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: A significant association was detected between rs11054731 in LRP6 intron 2 and CAD in our cohort (P = 0.001). The CC genotype and C allele frequency in the case group were 52% and 72%. Using a dominant model of inheritance, the C allele of rs11054731 was shown to be an independent risk factor for CAD with an OR of 1.45 (95%CI: 1.19 - 1.77, P = 0.0002). With the stratification according to the number of affected coronary arteries, an association was observed between rs11054731 and CAD (P = 0.0002). No significant association was observed between any other SNPs and the risk of CAD. CONCLUSION: The C allele of the rs11054731 within the LRP6 gene was associated with increased risk and extent of CAD in Chinese.

[Association study between TNFSF4 and coronary heart disease].

Previous studies suggest that TNFSF4 is a susceptibility gene of atherosclerosis. But case-control association analysis in Swedish population and German population provided inconsistent, even opposite results. In order to explore the relationship between this gene and coronary heart disease (CHD) in Chinese Han population, we collected 498 cases and 509 controls from Qilu hospital of Shandong University and analyzed the association between five single-nucleotide polymorphisms (SNPs) (rs1234314, rs45454293, rs3850641, rs1234313, and rs3861950) of TNFSF4 and CHD. On the basis of using traditional statistical analysis methods based on single SNP and haplotypes, we introduced principal component score-based logistic regression analysis to deal with the data. The results suggested that in Armitage trend test, only rs3861950 was significant, when used the Bonferroni correction, and all of the five SNPs were not statistically significant. In the logistic regression analysis which adjusts the confounding factors, all of the five SNPs were not statistically significant. In haplotype analysis, the frequencies of six haplotypes were significantly different in cases and controls (CTAGT (P=0.0006), CTAAC (P=0.0123), CCAGT (P=0.0004), GTGGT (P=0.0329), GCGAC (P<0.0001), and GCAAC (P=0.0173)). In principal component score-based logistic regression analysis, the first principal component has statistical significance (P=0.0236). These results indicate that TNFSF4 is a susceptibility gene of CHD in Chinese Han population.

Fibrobronchoscopic treatment of foreign body aspiration in children: an experience of 5 years in Hangzhou City, China.

OBJECTIVE: The aims of the study were to evaluate duration of symptoms, clinical manifestation, radiological findings, fibrobronchoscopic findings, and the complications of airway foreign body (FB). METHODS: A retrospective review of 304 children who had airway FB removed via fibrobronchoscopy from January 1997 to June 2003 was conducted in the Children's Hospital of Zhejiang University School of Medicine, China. Two hundred eight boys and 96 girls were included. Their ages ranged from 2 months to 11 years, and the median was 18 months. RESULTS: Three patients died; 81.24% of the patients had a history of FB aspiration, and the most frequent clinical manifestation was paroxysmal coughing (89.25%). Positive radiological findings were found in 90.13% of patients, and the most common type of FB was peanut (35.53%). Serious complication of lung was found in 65 patients, and the associated factors were age, sex, and times of fibrobronchoscopy and location of FB in the right or left lung. CONCLUSIONS: FB aspiration remains a major cause of morbidity and mortality in childhood. Education aimed at increasing diagnostic acumen of the physicians and heightening of public awareness are the most important steps needed to reduce the morbidity and mortality.