Comparison of the effects of probiotics, rifaximin, and lactulose in the treatment of minimal hepatic encephalopathy and gut microbiota.

Background: Minimal hepatic encephalopathy (MHE) is an early stage in the pathogenesis of hepatic encephalopathy. Intestinal microbiota is involved in the pathogenesis of hepatic encephalopathy and has become an important therapeutic target. Since there is no unified treatment principle for MHE, this study was conducted to determine the safety and efficacy of different intestinal microecological modulators in the treatment of MHE, and to explore the potential mechanism through intestinal microbiota analysis. Methods: Patients with liver cirrhosis were screened for MHE using psychometric hepatic encephalopathy score test. Patients diagnosed with MHE were enrolled and received probiotics, rifaximin, or lactulose for 4 weeks. Adverse events were recorded. The psychometric hepatic encephalopathy score test was performed after treatment. Samples of blood and stool were collected at entry and 4 weeks. Blood samples were analyzed to assess blood ammonia, liver, kidney, and hemostatic functions. Stool microbiota were sequenced to confirm changes in microbial composition. Results: Of 323 patients with liver cirrhosis, 74 patients were diagnosed with MHE. In all, 54 patients were enrolled and 52 who agree to follow-up were included in analysis. The recovery rates of MHE patients received probiotics, rifaximin, and lactulose were 58.8% (20/34), 45.5% (5/11), and 57.1% (4/7), respectively. Probiotics and rifaximin improved liver function in MHE patients to a certain extent. Taxonomic compositions of gut microbiota in MHE patients were distinct from healthy people before treatment; the differences were significantly reduced after treatment, and the gut microbiota gradually resembled the structure of healthy individuals. We found that the relative abundance of specific taxa associated with anti-inflammatory and good cognitive functions was increased in MHE patients after treatment. Accordingly, metabolic pathways in MHE patients were altered before and after treatment. Downregulated pathways after probiotics treatment included glycometabolism and degradation of aromatic compounds. After lactulose treatment, degradation pathways of arginine and ornithine showed a downward trend. Conclusion: Probiotics, rifaximin, and lactulose are safe and effective in the treatment of MHE, and improve the composition of gut microbiota to some extent.

Growth surveillance indices and Kashin-Beck Disease in children.

Selenium, manganese, and calcium are necessary elements for maintaining normal growth and skeleton formation. Kashin-Beck disease mostly occurs in children, resulting in deformities, dwarfism, and disabilities. Selenium deficiency was considered a risk factor in China, while manganese was reportedly involved in it in Russia. Single-element regulation cannot be used in diagnosis because of unclear boundaries in patients compared to healthy individuals. In this study, new indices of elements were designed to predict the status of disease. MS (Mn/Se), CS (Ca'/Se), and MC (Mn/Ca') values were designed, and prediction formulas were generated by comparing healthy children with those with Kashin-Beck disease via multiple linear regression analysis and discriminant analysis. In the disease group, 42.86% of patients had positive MS, CS, and MC values, and 57.14% of patients had positive MS and CS values. In the treatment group, the patients presented improved indices. In the prediction group, subjects with negative clinical criteria features were predicted by new indices, and 26.67% of them presented with positive MS, CS, and MC values, whereas 40.00% had positive MS and CS values. The 3D model of MS, CS, and MC refers to the setup of elements. The MS, CS, and MC indices are helpful in disease prediction, diagnosis, prognosis, and surveillance. The distribution model of the indices could serve in the growth surveillance of children.

Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis.

BACKGROUND AND AIMS: Rifaximin has been recommended as a prophylactic drug for hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). This study aims to explore whether low-dose rifaximin can prevent overall complications and prolong survival in cirrhotic patients. METHODS: In this multi-centre randomized open-labelled prospective study, 200 patients with decompensated cirrhosis were randomly assigned at a ratio of 1:1. Patients in rifaximin group were administered 400 mg rifaximin twice daily for 6 months, and all other therapeutic strategies were kept unchanged in both groups as long as possible. The primary efficacy endpoints were the incidence of overall complications and liver transplantation-free survival. The secondary endspoints were the incidence of each major cirrhosis-related complication, as well as the Child-Pugh score and class. RESULTS: The major baseline characteristics were similar in the two groups except for HE. The cumulative incidence and frequency of overall complications were significantly lower in rifaximin group than in the control group (p < 0.001). Though liver transplantation-free survival was not significantly different between the two groups, subgroup analysis showed rifaximin markedly prolonged liver transplantation-free survival in patients with Child-Pugh score ≥ 9 (p = 0.007). Moreover, rifaximin markedly reduced the episodes of ascites exacerbation (p < 0.001), HE (p < 0.001) and gastric variceal bleeding (EGVB, p = 0.031). The incidence of adverse events was similar in the two groups. CONCLUSION: Low-dose rifaximin significantly decreases the occurrence of overall complications, leading to prolonged survival in patients with advanced stages of cirrhosis in this trail. Further study should be carried out to compare the effect of this low-dose rifaximin with normal dose (1200 mg/day) rifaximin in preventing cirrhosis-related complications. CLINICAL TRIAL NUMBER: NCT02190357.

Cytoskeleton remodeling and oxidative stress description in morphologic changes of chondrocyte in Kashin-Beck disease.

Kashin-Beck disease (KBD) is a kind of deformity disease involved in cytoskeleton and inner homeostasis regulation. The enrichment analysis of bioprocess, networks, and related disease set were performed. The development regulation, metabolic process, and apoptosis were important procession in KBD; it revealed the up-regulated process in removal of superoxide radicals, glycolysis and glucose catabolic process, regulation of cytoskeleton rearrangement and phagosome in antigen presentation. Morphological changes of KBD chondrocyte were investigated by transmission electronic microscopy compare with the normal one. The ultrastructure of KBD chondrocyte referred to oxidative stress and metabolic dysfunction has been found.

MALDI-TOF-MS serum protein profiling for developing diagnostic models and identifying serum markers for discogenic low back pain.

BACKGROUND: The identification of the cause of chronic low back pain (CLBP) represents a great challenge to orthopedists due to the controversy over the diagnosis of discogenic low back pain (DLBP) and the existence of a number of cases of CLBP of unknown origin. This study aimed to develop diagnostic models to distinguish DLBP from other forms of CLBP and to identify serum biomarkers for DLBP. METHODS: Serum samples were collected from patients with DLBP, chronic lumbar disc herniation (LDH), or CLBP of unknown origin, and healthy controls (N), and randomly divided into a training set (n = 30) and a blind test set (n = 30). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed for protein profiling of these samples. After the discriminative ability of two most significantly differential peaks from each two groups was assessed using scatter plots, classification models were developed using differential peptide peaks to evaluate their diagnostic accuracy. The identity of peptides corresponding to three representative differential peaks was analyzed. RESULTS: The fewest statistically significant differential peaks were identified between DLBP and CLBP (3), followed by CLBP vs. N (5), DLBP vs. N (9), LDH vs. CLBP (20), DLBP vs. LDH (23), and LDH vs. N (43). The discriminative ability of two most significantly differential peaks was poor in classifying DLBP vs. CLBP but good in classifying DLBP vs. LDH. The accuracy of models for classification of DLBP vs. CLBP was not very high in the blind test (forecasting ability, 67.24%; sensitivity, 70%), although a higher accuracy was observed for classification of DLBP vs. LDH and LDH vs. N (forecasting abilities, ~90%; sensitivities, >90%). A further investigation of three representative differential peaks led to the identification of two peaks as peptides of complement C3, and one peak as a human fibrinogen peptide. CONCLUSIONS: Our findings benefit not only the diagnosis of CLBP but also the understanding of the differences between different forms of DLBP. The ability to distinguish between different causes of CLBP and the identification of serum biomarkers may be of great value to diagnose different causes of DLBP and predict treatment efficacy.

[Impact of evening exercise on college students' sleep quality].

OBJECTIVE: To investigate the impact of college students' evening exercise on their sleep quality, so as to provide a scientific basis for college students to choose an appropriate method of exercise and improve their sleep quality. METHODS: From September to October in 2012, Multi-stage cluster random sampling method was used to select the 5997 college students in Anhui province. The status of college students' exercise and their sleep quality were investigated by the general situation questionnaire, Physical activity rating scale-3(PARS-3), Rating of perceived exertion(RPE) and Pittsburgh sleep quality index(PSQI). Kruskal-Wallis test was used to analyze the impact of evening exercise on sleep quality and multivariate unconditional logistic regression was used to analyze the factors of sleep quality in evening excise students. RESULTS: The median of PSQI total score among 5806 college students was 5 and 1030(17.7%) students had poor sleep quality. The median of the PSQI scores was the same (5 points) for evening exercise group, daytime exercise group,daytime and evening exercise group and non-exercise group (1406, 1514, 1244, 1642 respectively). The difference was not statistically significant (χ(2) = 2.80, P = 0.42). Compared to non-exercise population, the OR (95%CI) value of evening exercise' impact on sleep quality was 0.90(0.73-1.10). Compared to very light evening exercise, the OR (95%CI) value of moderate and large amount of evening exercise' impact on sleep quality was 0.58 (0.44-0.75) and 0.67 (0.48-0.93) respectively; Compared to other sports, the OR (95%CI) value of badminton, rope skipping and jogging' impact on sleep quality was 0.72 (0.55-0.93), 0.38 (0.21-0.70) and 0.76 (0.60-0.95) respectively and they were all protective factors of sleep quality. Compared to small exercise intensity, the OR (95%CI) value of moderate, vigorous and very vigorous exercise intensity' impact on sleep quality was 1.68 (1.13-2.52), 2.38 (1.48-3.83) and 3.18 (1.72-5.90) respectively and they were harmful factors of sleep quality. CONCLUSION: There was no impact of evening exercise on sleep quality for college students. Type of sports should be adequately chosen for evening exercise. College students can take moderate and large amount of evening exercise but should avoid activities of vigorous intensity.

[Study on the relationship between college students' physical quality and the quality of sleep].

OBJECTIVE: The author wants to investigate the relationship between college students' physical quality and the quality of sleep. METHODS: Stratified cluster sampling method is used, and invites a total of 2981 Anhui college students to take part in the questionnaire study, the Pittsburgh sleep quality index (PSQI) and physical test, in order to survey the sleep quality and physical quality of college students. The physical quality and sleep quality are analyzed by the multiple factor non conditional logistic regression analysis methods. RESULTS: PSQI scores of the 2744 students are (5.378 ± 2.492), 477 people (17.4%) have poor sleep quality. The endurance, speed, strength quality scores are (75.850 ± 13.279), (69.760 ± 16.422), (66.278 ± 18.709) points. Logistic regression analysis shows that excellent endurance (OR = 0.418) is a protective factor of sleep quality. CONCLUSION: The improvement of endurance may improve sleep quality.

Proteomic changes in articular cartilage of human endemic osteoarthritis in China.

Kashin-Beck disease (KBD) is a chronic endemic osteochondropathy with unclear pathogenesis. It is a degenerative disease similar to osteoarthritis, but with different manifestations of cartilage damage. The aim of this investigation was to show the protein changes in KBD cartilage and to identify the candidate proteins in order to understand the pathogenesis of the disease. Proteins were extracted from the media of primary cell cultures of KBD and normal chondrocytes, and separated by two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). MALDI-TOF/TOF analysis revealed statistically significant differences in 27 proteins from KBD chondrocyte cultures, which consisted of 17 up-regulated and ten down-regulated proteins. The results were further validated by Western blot analysis. The proteins identified are mainly involved in cellular redox homeostasis and stress response (MnSOD, Hsp27, Peroxiredoxin-1, and Cofilin-1), glycolysis (PGK-1, PGM-1, α-enolase), and cell motility and cytoskeletal organization (Actin, Calponin-2, and Keratin). These KBD-associated proteins indicate that cytoskeletal remodeling, glycometabolism, and oxidative stress are abnormal in KBD articular cartilage.

Comparative analysis of gene expression profiles between primary knee osteoarthritis and an osteoarthritis endemic to Northwestern China, Kashin-Beck disease.

OBJECTIVE: To investigate the differences in gene expression profiles of adult articular cartilage from patients with Kashin-Beck disease (KBD) versus those with primary knee osteoarthritis (OA). METHODS: The messenger RNA expression profiles of articular cartilage from patients with KBD, diagnosed according to the clinical criteria for KBD in China, were compared with those of cartilage from patients with OA, diagnosed according to the Western Ontario and McMaster Universities OA Index. Total RNA was isolated separately from 4 pairs of the KBD and OA cartilage samples, and the expression profiles were evaluated by Agilent 4x44k Whole Human Genome density oligonucleotide microarray analysis. The microarray data for selected transcripts were confirmed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification. RESULTS: For 1.2 x 10(4) transcripts, corresponding to 58.4% of the expressed transcripts, 2-fold changes in differential expression were revealed. Expression levels higher in KBD than in OA samples were observed in a mean + or - SD 6,439 + or - 1,041 (14.6 + or - 2.4%) of the transcripts, and expression levels were lower in KBD than in OA samples in 6,147 + or - 1,222 (14.2 + or - 2.8%) of the transcripts. After application of the selection criteria, 1.85% of the differentially expressed genes (P < 0.001 between groups) were detected. These included 233 genes, of which 195 (0.4%) were expressed at higher levels and 38 (0.08%) were expressed at lower levels in KBD than in OA cartilage. Comparisons of the quantitative RT-PCR data supported the validity of our microarray data. CONCLUSION: Differences between KBD and OA cartilage exhibited a similar pattern among all 4 of the pairs examined, indicating the presence of disease mechanisms, mainly chondrocyte matrix metabolism, cartilage degeneration, and apoptosis induction pathways, which contribute to cartilage destruction in KBD.

5-aminosalicylic acid in combination with nimesulide inhibits proliferation of colon carcinoma cells in vitro.

AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5-ASA, nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining, respectively. RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 micromol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t=5.122, P<0.05; t=3.086, P<0.05, respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 micromol/L) or nimesulide (100 micromol/L) for 12-96 h, which showed an obvious time-effect relationship (t=6.149, P<0.05; t=4.159, P<0.05, respectively). At the concentration of 10-500 micromol/L, the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t=18.156, P<0.001; t=19.983, P<0.001, respectively), while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t=6.828, P<0.05; t=14.024, P<0.05, respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dose-dependent and time-dependent manner (t=5.448, P<0.05; t=4.428, P<0.05, respectively). CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.