[An epidemiologic study on functional constipation among adult communities in Shanghai].

OBJECTIVE: To determine the prevalence and risk factors of functional constipation (FC) by using Rome III criteria in the local adult communities. METHODS: A stratified randomized and community-based study by multi-stage cluster sampling was employed. A household survey was conducted from April to May 2010. All of the participants were interviewed face-to-face by filling out the self-administered questionnaires which based on Rome III criteria for the diagnosis of FC. Self-rating anxiety scale (SAS), self-rating depression scale (SDS) and Athens insomnia scale (AIS) were carried out to evaluate the psychological characteristics and qualities of sleep. RESULTS: A total of 7648 subjects fulfilled the questionnaires, with the response rate as 90.0%. 211 patients met the Rome III criteria, including 90 males and 121 females. The adjusted prevalence rates of FC were 2.5% in males, 3.3% in females and with an overall rate as 2.9%. The ratio of men to women was 1:1.32, with significant difference between males and females (P=0.043). The most common group was in the 18-29 year-olds (χ2=37.359, P=0.000). FC patients were more likely to be detected in the group with normal BMI (χ2=16.087, P=0.002), having received high education (χ2=27.604, P=0.000), being intelectuals (χ2=6.922, P=0.031) and divorced (χ2=22.000, P=0.000) than in other groups. Multivariate analysis showed that excessive intake of high-fat food was significantly associated with the presence of FC (odds ratio as 1.253, P=0.000), whereas foods with high-fiber (odds ratio as 0.854, P=0.029) might serve as protective factors. Significant differences between FC groups and control groups were found in the incidence of anxiety (with odds ratio as 2.583, P=0.000) and insomnia (odds ratio as 2.443, P=0.000). CONCLUSION: The prevalence of FC in adult communities in Shanghai Songjiang district was not higher than that in other parts of the communities. Excessive intake of high-fat food, anxiety and insomnia might be risk factors for FC and foods with high-fiber contents might serve as protective factors.

Functional gastrointestinal disorders among adolescents with poor sleep: a school-based study in Shanghai, China.

PURPOSE: This study aimed to determine whether functional gastrointestinal disorders are more common among adolescents with self-reported poor sleep. METHODS: Junior middle school and senior high school students (n = 1,362) were recruited from schools in Shanghai. Students completed two questionnaires: the questionnaire for irritable bowel syndrome (IBS) in adolescents and the Pittsburgh Sleep Quality Index. RESULTS: The prevalence of poor sleep was 34.29% [95% confidence interval (CI) = 31.77-36.81] and there was no significant difference between genders (P = 0.991). The tendency towards poor sleep increased with age, with age group yielding a significant effect (P = 0.001). In junior middle school and senior high school students, the propensity towards poor sleep was 30.10% (95% CI = 27.08-33.12%) and 42.11% (95% CI = 37.67-46.55%), respectively. Among students with poor sleep, the prevalence of IBS was 19.70% (95% CI = 16.09-23.31). After adjusting for age, sex, night pain, and psychological factors, IBS was significantly more common in students with poor sleep (odds ratio = 1.92; 95% CI = 1.07-2.58). CONCLUSION: We conclude that IBS is prevalent in students with poor sleep. Poor sleep was independently associated with IBS among adolescents in Shanghai China.

Prevalence and associated factors of functional gastrointestinal disorders and bowel habits in Chinese adolescents: a school-based study.

OBJECTIVES: In the present study, we explored the prevalence rates and association factors of functional gastrointestinal disorders and the most common modes and frequencies of bowel habit among a cohort of Chinese adolescents. PATIENTS AND METHODS: A stratified, randomized study based on cross-sectional data was performed using cluster sampling, which recruited 3671 students in Shanghai, China. All of the students were requested to complete a questionnaire. RESULTS: Overall, 88.05% ±â€Š0.28% of students had a bowel movement frequency of between 1 of 2 times per day and once every 2 days. Female students were found to have a lower bowel frequency than boys (P < 0.01). The prevalence of irritable bowel syndrome (IBS), functional constipation, and functional diarrhea were 19.89%, 24.93%, and 5.42%, respectively. Certain factors adjusted for age and sex were significantly associated with IBS (P < 0.05), including gastrointestinal tract infection (odds ratio [OR] 2.26), abuse of analgesics (OR 1.25), air swallowing to terminate hiccups (OR 1.28), fatigue (OR 1.15), and depression (OR 1.36). Other factors that were adjusted for age and sex, such as fried food (OR 1.68), air swallowing to terminate hiccups (OR 1.21), anxiety (OR 1.12), and depression (OR 1.57), were significantly associated with the presence of functional constipation (P < 0.05). CONCLUSION: : Our findings suggest that normal bowel frequency among Chinese urban adolescents may be defined as between 1 or 2 bowel movements per day and once every 2 days. IBS, functional constipation, and diarrhea are common disorders among this adolescent group.

[Effect of silencing connective tissue growth factor on the liver fibrosis in rats].

OBJECTIVE: To investigate the anti-fibrogenesis property of intraportal vein small interfering RNA (siRNA) injection targeting connective tissue growth factor (CTGF) in a rat model of liver fibrosis induced by carbon tetrachloride (CCl4) and its effect on hepatic stellate cell (HSC) activation. METHODS: 24 male rats were randomly divided into four group. rats received CCl4 by subcutaneous injections every three days for 6 consecutive weeks, and meantime they also obtained either siRNA targeting CTGF (as CTGF siRNA group), saline (as model group) or a control siRNA (as control siRNA group) by intraportal vein injection to rats liver at the same approach. Other rats received saline intraportal vein injection for 6 weeks (as normal control group). The expressions of CTGF and a-SMA protein were detected by Western blot. Hepatic histology was evaluated by HE staining and Sirius red staining. The collagen staining areas were measured quantitatively using a computer-aided manipulator with slight modifications. The number of active HSC were evaluated by immunohistochemistry. RESULTS: Six weeks after CCl4 injection, prominent upregulations were observed in the expressions of CTGF and a-SMA protein in saline or control siRNA-treated rats livers. In rats with CTGF siRNA treatment, the protein expressions of CTGF and a-SMA in liver decreased by 95%+/-2% and 86%+/-11% (F=21.234 and 12.473, P<0.01) respectively, the number of active HSC in liver decreased by 76%+/-9% (F=9.179, P<0.01) as compared to the model group. The attenuation of liver fibrosis was also observed in rats with CTGF siRNA treatment. CONCLUSION: Intraportal vein siRNA injection targeting CTGF could significantly inhibit CTGF gene expression in rats, thereby attenuate liver fibrosis by decreasing the number of active HSCs.

Preservation of basal AcSDKP attenuates carbon tetrachloride-induced fibrosis in the rat liver.

BACKGROUND & AIMS: N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an endogenous tetrapeptide which has antifibrogenic effects at physiological concentrations in various tissues. AcSDKP is produced locally in the liver, however, little is known about its biological effect in this organ. We hypothesize that basal levels of endogenous AcSDKP decrease during the development of liver fibrosis and preservation of basal AcSDKP attenuates liver fibrosis. METHODS: Endogenous levels of AcSDKP in the liver were measured by enzyme immunoassay after 2, 6, and 10 weeks of carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. Subcutaneous osmotic pump infusion of vehicle or AcSDKP (800 microg/kg/day) was administered to CCl(4)-treated rats for 8 weeks to study the effect of exogenous AcSDKP on liver fibrosis. The effect of AcSDKP on profibrogenic properties of hepatic stellate cells was studied in vitro. RESULTS: Endogenous AcSDKP was significantly decreased in the liver of CCl(4)-treated rats. Chronic AcSDKP infusion preserved basal levels of AcSDKP and reduced liver injury, inflammation, fibrosis, and profibrogenic transforming growth factor-beta signaling. This was demonstrated by decreased aminotransferase serum levels, CD45 positive cells, collagen accumulation, alpha-smooth muscle actin positivity, transforming growth factor-beta1, phosphorylated Smad2/3 protein, increased bone morphogenetic protein-7, and phosphorylated Smad1/5/8. Further, AcSDKP exerts antifibrogenic effects on hepatic stellate cells (HSCs) by downregulation of HSC activation in vitro. CONCLUSIONS: Maintaining physiological levels of AcSDKP is critical in negatively regulating the development of fibrosis in chronic liver injury. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.

Therapeutic effect of transplanting beta(2)m(-)/Thy1(+) bone marrow-derived hepatocyte stem cells transduced with lentiviral-mediated HGF gene into CCl(4)-injured rats.

BACKGROUND: beta(2)m(-)/Thy1(+) bone marrow-derived hepatocyte stem cells (BDHSCs) isolated from the bone marrow of cholestatic rats by magnetic bead cell sorting consistently express characteristics of both stem and liver cells. These stem cells may be good vehicles for gene transfer. Administration of exogenous hepatocyte growth factor (HGF) may be potentially useful for the treatment of liver fibrosis. Because lentiviral vectors integrate stably into the host-cell genome of nondividing and dividing cells, it may efficiently transfect beta(2)m(-)/Thy1(+) BDHSCs in vitro and secrete high-level HGF consistently. Transplantation of beta(2)m(-)/Thy1(+) BDHSCs transduced with lentiviral vectors containing the HGF gene may reduce liver fibrosis in rats. METHODS: Lentiviral vectors expressing HGF were constructed and used to transduce beta(2)m(-)/Thy1(+) BDHSCs sorted from cholestatic rats in vitro. Transduction efficiency was evaluated and then these cells were transplanted into rats through the portal vein. Liver function as well as histological and immunohistochemical examinations were carried out to assess the therapeutic efficacy on liver fibrosis. RESULTS: We demonstrated that high-level exogenous HGF was detected in supernatants after beta(2)m(-)/Thy1(+) BDHSCs were transfected with lentiviral vectors expressing HGF. Transplantation of transduced beta(2)m(-)/Thy1(+) BDHSCs significantly enhanced liver function and attenuated liver fibrosis in vivo. CONCLUSIONS: The present study indicates that transplantation of beta(2)m(-)/Thy1(+) BDHSCs overexpressing the HGF gene may offer a novel approach for promoting liver function and reverse liver fibrosis.

[Effect of interleukin 10 gene-modified bone marrow-derived liver stem cells transplantation on hepatic inflammatory response and liver regeneration in hepatic fibrosis rats].

OBJECTIVE: To explore effect of interleukin 10 (IL-10) gene-modified bone marrow-derived liver stem cells (BDLSCs) transplantation on hepatic inflammatory response and liver regeneration in rats with liver fibrosis. METHODS: 50 female Wistar rats were randomly divided into 4 groups: (1) control group: 10 rats were subcutaneously injected with olive oil for 8 weeks; (2) fibrosis groups: 16 rats were subcutaneously injected with carbon tetrachloride (CCl4) for 8 weeks to induce liver fibrosis; (3) BDLSC group: 12 rats were subcutaneously injected with CCl4 for 8 weeks, and were transplanted with 2 x 10(5) BDLSC at week 4; (4) BDLSC/IL-10 group: 12 rats were subcutaneously injected with CCl4 for 8 weeks, and were transplanted with 2 x 10(5) IL-10 gene-modified BDLSC at week 4. IL-10 and tumor necrosis factor alpha (TNFa) in liver tissues were detected by ELISA. HE stained liver tissues were observed under light microscope. The expression of hepatocyte growth factor (HGF) was quantified by real-time RT-PCR, and the expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry. RESULTS: The ratio of IL-10/TNFa in fibrosis group (0.05+/-0.01) was lower than that in control group (0.26+/-0.04) (P < 0.01). Transplantation of untreated BDLSCs did not improve the ratio (P > 0.05), however, transplantation of IL-10 modified BDLSCs improved the ratio significantly (P < 0.01). Severe inflammatory response and fibrosis were observed in fibrosis group. Inflammatory response was alleviated to some extent in the BDLSC group, and the histopathology of BDLSC/IL-10 group was not significantly different from that of the control group. Compared to the control group, the expression of HGF mRNA and PCNA protein was increased in the fibrosis group (P < 0.01). The expression of HGF and PCNA was further increased by BDLSCs or IL-10 modified BDLSCs transplantation. Compared to BDLSCs, IL-10 gene-modified BDLSCs were more potent to induce the expression of HGF and PCNA. CONCLUSION: Transplantation of IL-10 gene-modified BDLSCs can alleviate hepatic inflammatory response and promote liver regeneration in hepatic fibrosis rats.

Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells.

In our previous studies, we identified miR-16 as being downregulated during activation of hepatic stellate cells (HSCs) by microarray hybridization. However, the roles and related mechanisms of miR-16 in HSCs are not understood. In this study, The miRNA RNAi technique was used to analyze the effects of miR-16 on biological properties of HSCs in vitro. The lentiviral vector encoding miR-16 was constructed and transfected. Furthermore, the expression level of miR-16 was measured by real-time PCR. Cellular growth and proliferation capacity were assayed using the cell counting kit-8 (CCK-8). The apoptosis rate and cell-cycle distribution were measured by flow cytometry. Cell morphological characteristics were identified by phase-contrast microscopy, fluorescence microscopy and electron microscopy. The underlying mechanisms related to the changes in biological properties were assessed. The identity of the recombinant plasmid was confirmed by restriction endonuclease analysis and DNA sequencing. Virus titer was 10(8) > ifu/m. Restoring the intracellular miRNAs by miR-16 administration greatly reduced the expression levels of cyclin D1 (CD1). Cell-cycle arrest and typical features of apoptosis were detected in activated HSCs treated with pLV-miR-16. Our results indicate that transduction of miR-16 offers a feasible approach to significantly inhibit HSC proliferation and increase the apoptosis index. Thus, targeted transfer of miR-16 into HSC may be useful for the treatment of hepatic fibrosis.

Changes in microRNAs associated with hepatic stellate cell activation status identify signaling pathways.

Activation of hepatic stellate cells (HSCs), which is regulated by multiple signal transduction pathways, is the key event in liver fibrosis. Moreover, members of these pathways are important targets for microRNAs (miRNAs). To better understand the critical pathways of HSC activation, we performed comprehensive comparative bioinformatics analysis of microarrays of quiescent and activated HSCs. Changes in miRNAs associated with HSC activation status revealed that 13 pathways were upregulated and 22 pathways were downregulated by miRNA. Furthermore, mitochondrial integrity, based on highly upregulated Bcl-2 and downregulated caspase-9, was confirmed in HSCs and fibrotic livers by immnofluorescence assay, quantitative RT-PCR, and western blot analysis. These findings provide in vitro and in vivo evidence that the mitochondrial pathway of apoptosis plays a significant role in the progression of liver fibrogenesis via HSC activation.

miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: An essential role for apoptosis.

BACKGROUND/AIMS: To reveal the microRNA (miRNA) expression profile and related roles in rat HSCs during activation. METHODS: miRNA expression profiling was analyzed in quiescent and in culture-activated HSCs by microarray. The differentially expressed miRNAs, as verified by RT-PCR, were subjected to gene ontology (GO) analysis. Furthermore, the effects of miR-16 and miR-15b on the apoptosis of activated HSCs were investigated by Hoechst 33258, TUNEL staining and annexin-V/PI labeling flow cytometry. The underlying mechanism related to Bcl-2 and caspases was assessed. RESULTS: The upregulated and downregulated miRNAs in activated HSCs were 12 miRNAs and 9 miRNAs, respectively. The differential expression of miR-16, -15b, -122, -138, -143, and -140 was validated. High-enrichment GOs containing apoptosis-related targeted genes and miRNA-gene networks characterized by Bcl-2, which was targeted by the miR-15/16 family, uncovered the critical role of miR-16 and miR-15b in apoptosis. Restoring the intracellular miRNAs by miR-16 and miR-15b administration greatly reduced Bcl-2, and increased the expression of caspases 3, 8, and 9. Significantly elevated rates of apoptosis were then induced in activated HSCs. CONCLUSIONS: The activation of HSCs relate to 21 miRNAs. Among these, mir-15b and miR-16 may be essential for apoptosis by targeting Bcl-2 and the caspase signaling pathway.

[Risk factors of irritable bowel syndrome in adolescents in China].

OBJECTIVE: To explore the risk factors for irritable bowel syndrome (IBS) among school adolescents in China. METHOD: A stratified, randomized study by cluster sampling was conducted, which recruited 51,956 students from high and primary schools in Chinese cities. All students were requested to fill in a questionnaire. RESULT: (1) Factors including class (odds ratio 1.12), excessive intake of pepper (odds ratio 1.17), fried (odds ratio 1.08) and starch-based foods (odds ratio 1.06), gastrointestinal tract infection (odds ratio 2.66), abuse of analgesic (odds ratio 1.49), inheritance (odds ratio 1.83), fatigue (odds ratio 1.32) and repression (odds ratio 1.45) were significantly associated with the presence of IBS (P < 0.05). High protein food (odds ratio 0.90) was a protective factor. CONCLUSION: Different food intake, gastrointestinal tract infection, abuse of analgesic, inheritance and psychological factors might be related to development of IBS in the students of the cities involved in this study.

[Effects of gene-transfected bone marrow-derived liver stem cell transplantation on accumulation of extracellular matrix in rats with liver fibrosis].

OBJECTIVE: To explore the effects of urokinase-type plasminogen activator (uPA) gene-modified bone marrow-derived stem cell (BDLSC) transplantation on accumulation of extracellular matrix (ECM) in hepatic tissue in liver fibrosis. METHODS: BDLSCs obtained from 10 male Fisher344 rats were transfected by adenovirus-mediated human uPA (AduPA) in vitro. Twenty-seven female rats were randomly divided into 3 equal groups to undergo subcutaneous injection of carbon tetrachloride to establish liver fibrosis models and then randomly divided into 3 equal groups: model group injected with normal saline via caudal vein, BDLSC group injected with 2 x 10(6) BDLSCs via caudal vein, and BDLSC-uPA group injected with 2 x 10(6) AduPA-transfected BDLSCs. Eight weeks later the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), and ECM levels, i.e., hyaluronic acid, laminin (LN), and procollagen III (PC III), were detected. Then the rats were killed with their livers taken out. The hydroxyproline (Hyp) content of the liver was detected by alkaline hydrolysis. RT-PCR was used to examine the expression of collagen I and III (COLI and COLIII), matrix metalloproteinases-2, 3, and 9 (MMP-2, 3, and 9), and tissue inhibitor of metalloproteinase-1 and 2 (TIMP-1 and 2). RESULTS: Compared with those of the model group the levels of ALT, AST, and TBIL of the BDLSC-uPA group were all significantly lower, and the ALB level was higher (all P < 0.05). The ECM levels of BDLSC-uPA group were all significantly lower than those of the model group or BDLSC group too (all P < 0.05). Hyp content of the liver decreased dramatically. The mRNA expression levels of COLI and COLIII of the liver of the BDLSC-uPA group were significantly lower (38.9 +/- 2.7, 8.5 +/- 1.6), and the mRNA expression levels of MMP-2, -3, and MMP-9 mRNA (157.5 +/- 32.6, 105.5 +/- 14.6, 187.5 +/- 22.8) were significantly higher than those of the model group or BDLSC group (all P < 0.05), but no significant differences were observed in the mRNA expression of TIMP-1 and 2 mRNA between the 3 groups (all P > 0.05). CONCLUSION: uPA gene-modified BDLSC transplantation improves the liver function and suppresses the hepatic fibrosis in liver cirrhosis through up-regulating the expression of MMPs and promoting the degradation of ECM.

[Effects of silencing connective tissue growth factor on rat transforming growth factor beta/Smads signal].

OBJECTIVE: To investigate the effects of small interfering RNA targeting connective tissue growth factor (CTGF) on rat transforming growth factor beta (TGF beta)/Smads signal pathway. METHODS: Chemically synthetic siRNA targeting CTGF was transfected into HSC T6 and then they were injected into rat livers through their intraportal veins. At the same time these rats also received CCl4 subcutaneously every three days for 6 consecutive weeks. Untreated HSC T6 or/and rats with random siRNA treatment served as controls. Total RNA or/and protein in HSC T6 and rat hepatic tissues were extracted. The expressions of CTGF and TGF beta 1, Smad2, 3 and 7 genes were detected by reverse transcription-polymerase chain reaction (RT-PCR) and/or Western blot. RESULTS: CTGF siRNA significantly reduced the expression of CTGF protein in HSC T6. At 48 h after CTGF siRNA treatment, the down-regulation of CTGF protein was the most significant, up to 94%+/-4% (t=46.196, P less than 0.01), but the expressions of TGF beta 1, Smad2, 3 and 7 mRNA showed no differences in HSC T6 compared with the blank controls. Six weeks after CCl4 injections, prominent up-regulations were observed in the gene expressions of CTGF and TGF beta 1 in saline control or siRNA-treated rat livers. Administering CTGF siRNA for six weeks markedly attenuated the induction of CTGF and TGF beta 1 genes; the expressions of CTGF and TGF beta 1 protein decreased by 95%+/-2% (F=21.234, P less than 0.01) and 74%+/-8% (F=13.464, P less than 0.05), respectively, whereas Smad2, 7 protein expressions were not affected. CONCLUSION: Silencing the CTGF gene can suppress the TGF beta /Smads signal pathway in rat livers.

Transplantation of urokinase-type plasminogen activator gene-modified bone marrow-derived liver stem cells reduces liver fibrosis in rats.

BACKGROUND: Bone marrow-derived liver stem cells (BDLSCs) are very robust cells that can differentiate into liver epithelial cells. These stem cells are promising targets for gene therapy treatment of liver diseases. Liver fibrosis results from chronic liver damage characterized by an accumulation of extracellular matrix (ECM) and levels of urokinase-type plasminogen activator (uPA) play an important role in ECM degradation. In the present study, we investigated the therapeutic effects of uPA gene-modified BDLSC transplantation on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: BDLSCs were obtained from the bone marrow of cholestatic rats. These stem cells were selected and proliferated in medium containing 5% cholestatic serum. BDLSCs transfected with adenovirus-mediated human urokinase-plasminogen activator were transplanted into rats with CCl(4)-induced hepatic fibrosis. Liver function and the area of hepatic fibrosis were correlated with the development and prognosis of hepatic fibrosis. RESULTS: Hepatocyte-like colony-forming units were formed by bone marrow cells after 2 weeks in culture. In the uPA gene-modified BDLSC group, the areas of hepatic fibrosis were smaller and liver function was markedly ameliorated compared to controls. The expression of alpha-smooth muscle actin protein, transforming growth factor-beta1 protein and collagen types I and III mRNA were downregulated. By contrast, the levels of matrix metalloproteinases-2, -3 and -9 mRNA, hepatic growth factor mRNA and proliferating cell nuclear antigen protein increased. CONCLUSIONS: Transplantation of uPA gene-modified BDLSCs may suppress hepatic fibrosis and ameliorate liver function.

[Effect of silencing connective tissue growth factor on rat liver fibrosis and the accumulation of extracellular matrix].

OBJECTIVE: To investigate the anti-fibrogenesis property of intraportal vein injection of small interfering RNA targeting connective tissue growth factor (CTGF) in a rat model of liver fibrosis and its effect on the accumulation of extracellular matrix (ECM). METHODS: Thirty male rats were randomly divided into five groups. Some rats received CCl4 subcutaneously every three days for 6 consecutive weeks, and in the meantime they also received either siRNA targeting CTGF (preventive group), saline (model group) or siRNA (siRNA control group) by intraportal vein injections. Other rats received CCl4 by subcutaneous injection for 2 weeks, followed by CCl4 and CTGF siRNA intraportal vein injection for 4 more weeks (as treatment group). The expressions of CTGF and type I and III collagen genes were detected by means of reverse transcription-polymerase chain reaction (RT-PCR) and/or Western blot respectively. Hepatic histology was evaluated by HE and Sirius red stained sections. The collagen staining areas were measured quantitatively using a computer-aided manipulator with slight modifications. Serum procollagen type III and hyaluronic acid were determined by radioimmunoassay. RESULTS: Six weeks after CCl4 injection, prominent upregulation of gene expressions of CTGF, type I and III collagen, and laminin in saline or siRNA-treated rat livers were observed. The expressions of CTGF at mRNA and protein level and type I and III collagen at mRNA level were markedly reduced in rats with CTGF siRNA treated for four or six weeks. Expressions of CTGF at mRNA and protein levels decreased by 76%+/-8%, 80%+/-3% (F = 68.630) and 95%+/-2%, 93%+/-3% (F = 21.234, P < 0.01); type I and III collagen and laminin at mRNA levels decreased by 74%+/-8%, 78%+/-8%, 31%+/-7% and 57%+/-6%, 59%+/-10%, 43%+/-9% (F = 24.219, 16.315, 9.716, P < 0.01) compared with rats in the model group at 72 h. The CTGF siRNA treatment markedly reduced serum levels of procollagen type III and hyaluronic acid and the degrees of liver fibrosis. CONCLUSION: Intraportal vein siRNA injection targeting CTGF could significantly inhibit CTGF gene expression in rats, thereby attenuating liver fibrosis by reducing ECM accumulation.

[An epidemiologic study of functional bowel disorders in adolescents in China].

OBJECTIVE: To explore the most common bowel frequency and the prevalence rates of functional bowel disorders among adolescents in China. METHODS: A questionnaire survey was conducted among 51,956 students from high and primary schools in 6 Chinese cities distributed in the whole China collected by stratified, randomized, cluster sampling to study the epidemiology of functional bowel disorders. RESULTS: (1) 88.05% +/- 0.28% of the students had bowel frequency between 1 - 2 times/day and 1 time/two days. Girl students were found to have a lower bowel frequency than boy students (P < 0.01). (2) The prevalence rates of irritable bowel syndrome, chronic constipation, and chronic diarrhea were 20.19% (10 490), 25.92% (13 467), and 8.77% (4557) respectively. CONCLUSION: (1) The normal bowel frequency among adolescents in China may be defined as bowel movements between 1 - 2 times per day and 1 time per two days. (2) Irritable bowel syndrome, chronic constipation and chronic diarrhea are common disorders among the adolescents in China.

[An epidemiologic study of irritable bowel syndrome among adolescents in China].

OBJECTIVE: To explore the prevalence of irritable bowel syndrome (IBS) and its distribution characteristics among adolescents in China. METHODS: A stratified and randomized study by cluster sampling was employed, the study recruited 51 956 students from high and primary schools in different Chinese cities. All students were requested to fill in a questionnaire. RESULTS: The prevalence of IBS in China was 53.5% according to the Manning criterion and 20.2% according to the Rome II criterion. The prevalence in male and female students showed no significant difference (P>0.05), but there was higher prevalence of IBS in high school students. The prevalence of IBS was 53.3% according to the Manning criterion and 19.6% according to the Rome II criterion in south China. The prevalence of IBS was 51.2% according to the Manning criterion and 18.9% according to the Rome II criterion in North China. The prevalence of IBS was 58.0% according to the Manning criterion and 23.4% according to the Rome II criterion in west China. CONCLUSION: IBS is a common disorder among the adolescents and the prevalence of IBS is increasing with increase of age in adolescents.

Modified synthetic siRNA targeting tissue inhibitor of metalloproteinase-2 inhibits hepatic fibrogenesis in rats.

BACKGROUND/AIMS: Fibrosis occurs in most chronic liver injuries and results from changes in the balance between synthesis and degradation of extracellular matrix (ECM) components. Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) are known to regulate the ECM turnover. We investigate the effect of modified synthetic small interfering RNA (siRNA) targeting TIMP-2 in rat model of liver fibrosis. METHODS: Rat hepatic fibrosis was induced by CCl4 for 8 weeks. After the 2-week CCl4 injection period, rats in the three siRNA groups simultaneously received a different dosage (0.05, 0.1 and 0.2 mg.kg(-1), respectively) of modified synthetic siRNA targeting TIMP-2 via the tail vein every 3 days for 6 weeks. The pathological changes in liver tissues were observed by light microscopy and transmission electron microscopy. Portal vein pressure and proliferating cell nuclear antigen were measured. Expression of TIMP-2, MMP-2, MT1-MMP, MMP-13, hepatocyte growth factor, collagen type I, collagen type III and alpha-SMA were evaluated by quantitative real-time polymerase chain reaction or Western blotting or gelatin zymography. RESULTS: Modified synthetic siRNA targeting TIMP-2 induced a dose-dependent inhibition of the TIMP-2 expression in the rat model of liver fibrosis with a similar trend in MMP-2 and MT1-MMP, but an increase in MMP-13. Rats administered siRNA targeting TIMP-2 showed promotion of ECM degradation, reduction in activated hepatic stellate cells and enhancement of hepatocyte regeneration. Furthermore, portal hypertension was also ameliorated after treatment with siRNA targeting TIMP-2. CONCLUSIONS: Knock-down of TIMP-2 expression attenuates CCl4-induced liver fibrosis and is a potential pharmacological target for gene therapy in liver fibrosis.