Yinzhihuang attenuates ANIT-induced intrahepatic cholestasis in rats through upregulation of Mrp2 and Bsep expressions.

BACKGROUND: The treatment of intrahepatic cholestasis has been limited, and development of an effective drug is needed. Clinical studies have shown that Yinzhihuang (YZH), a traditional Chinese decoction, enhances bilirubin clearance. The goal of this study was to determine the protective effect of YZH on experimental intrahepatic cholestasis in young rats and to explore its underlying molecular mechanisms. METHODS: Intrahepatic cholestasis in rats was induced by α-naphthylisothiocyanate (ANIT) on days 1 and 8. The rats received YZH, ursodeoxycholic acid (UDCA), or vehicle for 9 d and were killed on either day 3 or day 10. Serum biomarkers, liver histology, and the distribution of protein and mRNA expression of Mrp2 and Bsep were analyzed. RESULTS: YZH treatment resulted in decreased levels of serum biomarkers except γ-glutamyl transpeptidase, attenuated liver histological injuries, increased protein expressions of Mrp2 and Bsep, and upregulated expressions of Mrp2 and Bsep mRNAs. The effects of YZH on serum biomarkers (aminotransferase, alanine aminotransferase, and direct bilirubin), liver histology, and Mrp2 mRNA expressions were significantly greater and earlier than those of UDCA. CONCLUSION: Our results suggest that YZH has protective effect against ANIT-induced intrahepatic cholestasis in rats, through upregulation of Mrp2 and Bsep expressions.

Short-term effects of meteorological factors on pediatric hand, foot, and mouth disease in Guangdong, China: a multi-city time-series analysis.

BACKGROUND: Literature shows inconsistency in meteorological effects on Hand, foot, and mouth disease (HFMD) in different cities. This multi-city study aims to investigate the meteorological effects on pediatric HFMD occurrences and the potential effect modification by geographic factors. METHODS: Based on daily time-series data in eight major cities in Guangdong, China during 2009-2013, mixed generalized additive models were employed to estimate city-specific meteorological effects on pediatric HFMD. Then, a random-effect multivariate meta-analysis was conducted to obtain the pooled risks and to explore heterogeneity explained by city-level factors. RESULTS: There were a total of 400,408 pediatric HFMD cases (children aged 0-14 years old) with an annual incidence rate of 16.6 cases per 1,000 children, clustered in males and children under 3 years old. Daily average temperature was positively associated with pediatric HFMD cases with the highest pooled relative risk (RR) of 1.52 (95 % CI: 1.30-1.77) at the 95th percentile of temperature (30.5 °C) as compared to the median temperature (23.5 °C). Significant non-linear positive effects of high relative humidity were also observed with a 13 % increase (RR = 1.13, 95 % CI: 1.00-1.28) in the risk of HFMD at the 99th percentile of relative humidity (86.9 %) as compared to the median value (78 %). The effect estimates showed geographic variations among the cities which was significantly associated with city's latitude and longitude with an explained heterogeneity of 32 %. CONCLUSIONS: Daily average temperature and relative humidity had non-linear and delayed effects on pediatric HFMD and the effects varied across different cities. These findings provide important evidence for comprehensive understanding of the climatic effects on pediatric HFMD and for the authority to take targeted interventions and measures to control the occurrence and transmission of HFMD.

The impact of relative humidity and atmospheric pressure on mortality in Guangzhou, China.

OBJECTIVE: Although many studies have examined the effects of ambient temperatures on mortality, little evidence is on health impacts of atmospheric pressure and relative humidity. This study aimed to assess the impacts of atmospheric pressure and relative humidity on mortality in Guangzhou, China. METHODS: This study included 213,737 registered deaths during 2003-2011 in Guangzhou, China. A quasi-Poisson regression with a distributed lag non-linear model was used to assess the effects of atmospheric pressure/relative humidity. RESULTS: We found significant effect of low atmospheric pressure/relative humidity on mortality. There was a 1.79% (95% confidence interval: 0.38%-3.22%) increase in non-accidental mortality and a 2.27% (0.07%-4.51%) increase in cardiovascular mortality comparing the 5th and 25th percentile of atmospheric pressure. A 3.97% (0.67%-7.39%) increase in cardiovascular mortality was also observed comparing the 5th and 25th percentile of relative humidity. Women were more vulnerable to decrease in atmospheric pressure and relative humidity than men. Age and education attainment were also potential effect modifiers. Furthermore, low atmospheric pressure and relative humidity increased temperature-related mortality. CONCLUSION: Both low atmospheric pressure and relative humidity are important risk factors of mortality. Our findings would be helpful to develop health risk assessment and climate policy interventions that would better protect vulnerable subgroups of the population.

[Extraintestinal dissemination of rotavirus in immunodeficient mice].

OBJECTIVE: To investigate the extraintestinal dissemination of rotavirus (RV) in immunodeficient mice. METHODS: Immunodeficiency mouse model was established by injection of cyclophosphamide into the abdominal cavities of normal mice, then to which RV was administered either orally or intra-abdominally. The pathological changes in the organs were observed by light microscopy and RV was detected by in situ hybridization and PCR. RESULTS: Small intestinal villi, gastric lamina propria and cardiac myocytes exhibited pathological changes in the mice with oral RV administration. Besides these changes, the mice with intra-abdominal RV injection showed changes in the liver and kidneys. The intestinal villi of the mice with oral RV were RV positive by in situ hybridization. Positive results of RV in in situ PCR detection were found in the intestinal villi, intestinal gland cells, epithelial cells of the proximal convoluted tubules and collecting tubes in the kidney of the mice taken RV orally, and in the intestinal villi, kidneys, liver, heart and pancrease of mice with intra-abdominal RV injection. CONCLUSION: Immunodeficiency may be the important factor for inducing and aggravating the infection and extraintestinal dissemination of RV.

[Epidemiological and clinical analysis of Mycoplasma pneumoniae infection in children with acute respiratory tract infection].

OBJECTIVE: To summarize the epidemiology and clinical characteristics of Mycoplasma pneumoniae (MP) infection in children with acute respiratory tract infection (ARI) in Guangzhou. METHODS: MP was detected using an indirect immunofluorescent method in 2084 children with ARI. The relations between MP infection rate and the gender, age, season, site of infection and wheezing diseases were analyzed. RESULTS: A total of 433 children (20.8%) were positive for MP, including 222 boys (19.8%) and 211 girls (21.9%) without significant difference in the infection rate between the genders (P>0.05). In 0- to 3-year-old group, 106 children were positive for MP (15.0%), while in 3- to 5-year-old group and 5- to 14-year-old group, 163 (25.2%) and 164 (22.5%) were positive, respectively, showing a significant difference in the infection rate between the 3 groups (P<0.05). The MP infection rate was 18.0% in January to March, 25.1% in April to June, 17.7% in July to September, and 20.5% in October to December, showing significant differences between the periods (P<0.05). No significant difference was found in the infection rate between children with acute upper respiratory tract infection (URI) and those with lower respiratory tract infection (LRI) (P>0.05). Among the children with LRI, those having wheezing disease had significantly higher MP positivity rate than those without wheezing. CONCLUSION: MP is a common causative agent for ARI in children. MP infection is not related to gender and infection site, but to age and season. Children over 3 years old are vulnerable to MP infection. MP infection can be associated with wheezing in LRI.

[Factors triggering extraintestinal infection of rotavirus].

OBJECTIVE: To investigate the role of immunodeficiency and intestinal mixed infection on inducing extraintestinal dissemination of rotavirus (RV). METHODS: Immunodeficiency was induced in healthy Kunming mice by introperitoneal injection of cyclophosphamide, and RV was administered either orally or via intraperitoneal injection. In another group, toxigenic E. coli and human RV were given sequentially by intragastric administration to induce mixed infection. Three days later the organs of the mice were taken for pathological examination, and RV was detected by in situ PCR and hybridization. In children with or without viremia of rotavirus, blood tests for levels of tumor necrosis factor alpha (TNF-alpha), interleukin-2 (IL-2) and 7 trace elements (zinc, iron, copper, lead, calcium, manganese, and magnesium) were performed. RESULTS: In immunodeficient mice, pathological changes were found in the small intestinal villus, gastric lamina propria and the cardiac cells of mice taking RV orally, and the mice with intraperitoneal RV injection showed additional liver and kidney pathologies. In mice with mixed infections, pathological changes occurred in the intestines, livers and kidneys. In situ hybridization detected RV in the intestinal villus of immunodeficient mice with oral RV administration, and in the intestinal villus and kidneys of the mice with mixed infections. In situ PCR revealed the presence of RV in the intestinal villus, intestinal gland cells, epithelial cells of the proximal convoluted tubules and collecting tubes in the kidneys of immunodeficient mice taking RV orally, in the intestinal villus, kidneys, livers, hearts and pancreases of those with RV injection, and in the intestines, kidneys, and livers of the mice with mixed infection. Children with rotavirus viremia had TNF-alpha level in comparison with those free of rotavirus viremia, and the majority of the former children showed disorder in trace elements. CONCLUSION: Immunodeficiency, mixed infection and malnutrition can be important factors contributing to or exacerbating RV infection and extraintestinal RV dissemination.

[Ultrastructural changes of the extraintestinal organs of newborn mice with human rotavirus infection].

OBJECTIVE: To investigate the ultrastructural changes of the extraintestinal organs of newborn mice with human retrovirus (RV) infection to probe into the mechanism and clinical diagnose and therapy of extraintestinal RV infection. METHODS: Human RV was inoculated into the abdominal cavity of the newborn mice, and the ultrastructural changes of the heart, lung, livers, and kidneys of the infected and control mice were observed by transmission electron microscope. RESULTS: The mice with intraabdominal RV injection showed pathological changes of the cells in the small intestinal villus, liver, and kidneys. Shortened small intestinal villus, nuclear membrane disorganization, massive vacuolization, mitochondrial swelling and rough endoplasmic reticulum dilation were observed in the cells of the small intestinal. In the liver of the mice, marked mitochondrial swelling and agglutination, cell nucleus pyknosis or collapse, presence of numerous lipid droplets and vacuoles were seen in the liver cells, with lymphocyte and plasmacyte infiltration. Obvious dilatation and shedding of the microvillus were seen in cholangioles. The mitochondria of the proximal convoluted renal tubule showed mild swelling, but the cells in the heart and lung did not display obvious changes. CONCLUSION: The small intestinal villi were highly susceptible to RV infection, and systemic spread of human RV may cause damage of various extraintestinal organs especially the liver, which can also be susceptible to RV.