Berberine Enhances Intestinal Mucosal Barrier Function by Promoting Vitamin D Receptor Activity.

OBJECTIVE: To evaluate if berberine can act on vitamin D receptors (VDR) and thereby regulate the expression of tight junction proteins (TJPs) in irritable bowel syndrame-diarrhea-predominant (IBS-D) rats. METHODS: The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical stimulation. After modeling, the model was evaluated and rats were divided into the control group and berberine treatment groups (0.85, 1.7 and 3.4 mg/kg, once a day for 2 weeks). The distal colon was obtained and colonic epithelial cells (CECs) were isolated and cultured after IBS-D model evaluation. The vitamin D receptor response element (VDRE) reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE promoter. VDR overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair, and to determine which region of VDR plays a role in berberine-regulated intestinal TJPs. RESULTS: The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner (P<0.05). The activity of VDRE promoter was also effectively promoted by berberine (P<0.05). Berberine increased the expression of TJPs in IBS-D CECs (P<0.05). VDR expression was significantly increased after transfection of different domains of VDR when compared to normal control and basic plasmid groups (all P<0.05). RT-qPCR and Western blot results showed that compared with the blank group, expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups (all P<0.05). Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1 (P<0.05). CONCLUSION: Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity, and the main site of action is the N-terminal region of VDR.

Yangzheng Sanjie decoction regulates proliferation and apoptosis of gastric cancer cells by enhancing let-7a expression.

AIM: To explore the let-7a-mediated anti-cancer effect of Yangzheng Sanjie decoction (YZSJD) in gastric cancer (GC) cells. METHODS: YZSJD-containing serum (YCS) was prepared using traditional Chinese medicine serum pharmacology methods. After YCS treatment, cell proliferation and apoptosis were assessed by cell counting kit-8 assay and flow cytometry, respectively, and miRNA expression profiles were determined using qPCR arrays. Let-7a expression was examined by in situ hybridization in GC tissues and by qPCR in GC cells. c-Myc protein expression was detected by immunohistochemistry in GC tissues, and by Western blot in cell lines. RESULTS: YZSJD significantly inhibited proliferation and induced apoptosis in AGS and HS-746T GC cells. After treatment with YCS, the miRNA expression profiles were altered and the reduced let-7a levels in both cell lines were up-regulated, accompanied by a decrease in c-Myc expression. Moreover, decreased let-7a expression and increased c-Myc expression were observed during the progression of gastric mucosa cancerization. CONCLUSION: YZSJD inhibits proliferation and induces apoptosis of GC cells by restoring the aberrant expression of let-7a and c-Myc.

Multi-host model and threshold of intermediate host Oncomelania snail density for eliminating schistosomiasis transmission in China.

Schistosomiasis remains a serious public health issue in many tropical countries, with more than 700 million people at risk of infection. In China, a national integrated control strategy, aiming at blocking its transmission, has been carried out throughout endemic areas since 2005. A longitudinal study was conducted to determine the effects of different intervention measures on the transmission dynamics of S. japonicum in three study areas and the data were analyzed using a multi-host model. The multi-host model was also used to estimate the threshold of Oncomelania snail density for interrupting schistosomiasis transmission based on the longitudinal data as well as data from the national surveillance system for schistosomiasis. The data showed a continuous decline in the risk of human infection and the multi-host model fit the data well. The 25th, 50th and 75th percentiles, and the mean of estimated thresholds of Oncomelania snail density below which the schistosomiasis transmission cannot be sustained were 0.006, 0.009, 0.028 and 0.020 snails/0.11 m(2), respectively. The study results could help develop specific strategies of schistosomiasis control and elimination tailored to the local situation for each endemic area.

Role of microRNA-7 in digestive system malignancy.

There are several malignancies of the digestive system (including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwide. MicroRNA (miR)-7 is abundant in the pancreas, playing an important role in pancreatic development and endocrine function. Expression of miR-7 is downregulated in digestive system malignancies compared with normal tissue. Although there are contrasting results for miR-7 expression, almost all research reveals that miR-7 is a tumor suppressor, by targeting various genes in specific pathways. Moreover, miR-7 can target different genes simultaneously in different malignancies of the digestive system. By acting on many cytokines, miR-7 is also involved in many gastrointestinal inflammatory diseases as a significant carcinogenic factor. Consequently, miR-7 might be a biomarker or therapeutic target gene in digestive system malignancies.

Traditional Chinese medicine versus western medicine as used in China in the management of rheumatoid arthritis: a randomized, single-blind, 24-week study.

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.

Spatial-temporal variations of Schistosoma japonicum distribution after an integrated national control strategy: a cohort in a marshland area of China.

BACKGROUND: Schistosomiasis transmission is typically focal. Understanding spatial variations of Schistosoma infections and their associated factors is important to help to invent site-specific intervention strategies. METHODS: A five-year longitudinal study was carried out prospectively in 12 natural villages, Guichi district of Anhui province. A GIS-based spatial analysis was conducted to identify geographic distribution patterns of schistosomiasis infections at the household scale. RESULTS: The results of the spatial autocorrelation analysis for 2005 showed that there were significant spatial clusters of human infections at the household level, and these results were in agreement with that of the spatial scan statistic. As prevalence of infections in humans decreased over the course of control, the spatial distribution of these infections became less heterogeneous. CONCLUSIONS: The findings imply that it may be necessary to re-assess risk factors of S. japonicum transmission over the course of control and to adjust accordingly control measures in the communities.

[Molluscicidal effects of nano-silver biological molluscicide and niclosamide].

OBJECTIVE: To evaluate the molluscicidal effect of a novel nano-silver biological molluscicide in the field and its toxicity to other aquatic organisms. METHODS: A marshland of the Qiupu River was selected as the study site. Four 1 m3 pools were excavated. Four groups, including 300 g/m3 and 600 g/m3 nano-silver biological molluscicide groups, a 2 g/m3 50% niclosamide group, and a natural water (control) group were assigned to the four pools which had 100 Oncomelania hupensis snails and 100 crucian seedlings. The molluscicidal effects and toxicity to the aquatic organisms were observed. RESULTS: The snail death rates were 100% and crucian seedling death rates were 6% in the 600 g/m3 nano-silver biological molluscicide group and 300 g/m3 nano-silver biological molluscicide group in 7 days and 14 days. The snail death rate was 100% in the niclosamide group in 7 days, and the crucian seedling death rate was 100% in the niclosamide group in 3 days. The snail death rates were 7% and 14% in the control group in 7 and 14 days respectively, and the crucian seedling death rate was 22% in the control group. CONCLUSIONS: The novel nano-silver biological molluscicide possesses an excellent molluscicidal capability and non-toxicity to the other aquatic organisms. Therefore, it may become a new, efficient and environment-friendly bio-molluscicide for extensive application.

[Evaluation on the effect of comprehensive control strategy of schistosomiasis with emphasis on infection source control in Anhui province].

OBJECTIVE: To evaluate the effect of comprehensive control strategy of schistosomiasis with emphasis on infection source control in Anhui province. METHODS: Forty endemic villages in Guichi district, Chizhou city, Anhui province were selected as national pilot villages in the years from 2006 to 2008, and another 10 provincial pilot villages were respectively selected from 10 highly endemic villages in 7 cities in 2007. The comprehensive infection source control measures, including "replace cattle with machines", "raise livestock in pens", "improve the sanitary toilets", "supply safe water " and so on were carried out among the above pilot villages. At the end of 2008, 13 national pilot villages and 6 provincial pilot villages were selected to investigate the popularity of schistosomiasis, and the effect of the comprehensive control strategy in those villages were compared. RESULTS: After implementing the comprehensive control strategy, the infectious rate of schistosomiasis in national pilot villages decreased from 4.57% (487/10 659) to 1.76% (147/8370), with the reduction rate at 61.49%, whose difference showed statistical significance (χ(2) = 115.16, P < 0.01); and the density of infected snails decreased from 0.0067/0.1 m(2) to 0.0008/0.1 m(2), the infectious rate of snails decreased from 0.28% to 0.04%, whose reduction rates were 88.06% and 85.71% respectively. While as to the provincial pilot villages, the infectious rate of schistosomiasis decreased from 1.27% (54/4254) to 0.21% (14/6592), with the reduction rate at 83.46%, whose difference showed statistical significance (χ(2) = 94.57, P < 0.01); and the density of infected snails decreased from 0.0025/0.1 m(2) to 0.0003/0.1 m(2), the infection rate of snails decreased from 0.13% to 0.05%, whose reduction rates were 88.00% and 61.54% respectively. CONCLUSION: The comprehensive control strategy with emphasis on infection source control implemented in marshland and lake regions can effectively control the transmission of schistosomiasis.

[Investigation on prevalent trends and analysis of control period among floating population in schistosomiasis endemic areas of Guichi District].

OBJECTIVE: To understand the characteristics of the floating population infected with Schistosoma japonicum, so as to provide the evidence for constituting and optimizing control strategy. METHODS: By the cluster random sampling method, six highly endemic villages from the different endemic types in Guichi District were selected as the research areas . The basic information and infected status of the floating population were surveyed by questionnaires and examination between 2000 and 2009. RESULTS: The time when the floating population returned to their homes mainly focused on Spring Festival between 2000 and 2009, and more than 83% of people returned. The infection rate of the floating population was similar to or more than that of the local residents. During the ten years, the reduction of the infection rates in the floating populations (from 5.29% to 2.63%) was consistent with the reduction of the infection rates in the local residents (from 5.28% to 2.68%). However, the reduction of the infection rates in the floating population who worked in the non-endemic areas was more than that in the local residents. CONCLUSION: Spring Festival is the optimal time for detecting and treating schistosomiasis in the floating population.

An integrated strategy for transmission control of Schistosoma japonicum in a marshland area of China: findings from a five-year longitudinal survey and mathematical modeling.

In 2004 an aggressive plan was instituted aiming to achieve nationwide transmission control of schistosomiasis by 2015. Here, we report a longitudinal study on the control of schistosomiasis in Anhui province, China. Using a mathematical model, we compared the effects of different control strategies implemented in the study area. During the 5-year study period, a 60.8% reduction in human prevalence was observed from 2005 (7.95%) to 2009 (3.1%), and snail infection decreased from 0.063% in 2005 to zero in 2009. Results of the model agree well with the first 3-year field observations and suggest continuous decrease in human infections in the last 2 years, whereas the last 2-year field observations indicated that human infections appeared to be stable even with continuous control. Our findings showed that the integrated control strategy was effective, and we speculated that other factors besides bovines might contribute to the local transmission of the disease.

[Comparison of cost between two ways of skin grafting in the treatment of patients with extensive deep burn].

OBJECTIVE: To evaluate the economic significance of Meek skin grafting and automicrografting combined with large piece of allogenous skin (micrografting in brief) in the treatment of patients with extensive deep burn. METHODS: Twenty-four patients with extensive deep burn admitted to the First Affiliated Hospital of Wenzhou Medical College were divided into Meek skin grafting group and micrografting group, with 12 patients in each group. Statistical comparison between Meek skin grafting group and micrografting group in respect of wound healing time, consumption of each special dressing, total cost of hospitalization, rehabilitation cost during convalescence was made. Then the cost and effect value was compared between two groups. RESULTS: The wound healing time, consumption of each special dressing, total cost of hospitalization and rehabilitation cost in Meek skin grafting group was (14.4 +/- 1.9) d, yen(16 590 +/- 521), yen(421 628 +/- 145), yen(39 571 +/- 225), respectively, and that in micrografting group was (25.6 +/- 4.2) d, yen (136 441 +/- 356), yen(539 526 +/- 686), yen(55 853 +/- 794), respectively. The difference between two groups were statistically significant (P < 0.01). CONCLUSIONS: In a definite range of burn size, Meek skin grafting has a lower therapeutic cost and better therapeutic effects as compared with micrografting.

[Study on the quantified indices to describe the distributional status of diseases in the spatial point pattern analysis].

OBJECTIVE: To study the quantified indices for describing the distributional status of diseases in the spatial point pattern analysis, and provide the a statistic in disease prevention and control. METHODS: G function, F function, J function and K function were summarized based on the inter-case distances from the view of spatial point pattern analysis. Through the introduction of the basic principles, these were used to analyze the data of acute schistosomiasis in the Guichi District, Chizhou City, Anhui province, with the study distances being from 0 to 3000 meters with 50-meter intervals. The findings were also validated by means of spatial moving scan window performed in SaTScan software. RESULTS: A total of 83 cases of acute schistosomiasis identified in Guichi District, and the point map showed that these cases were mainly distributed around the Yangtze and Qiupu rivers. The computational methods and characteristics of the four quantified indices were obtained. These acute schistosomiasis cases were also explored by using these indices, and the results showed that C and K functions were above 95% confidence interval. While, F and J functions were below 95% confidence interval. Ml these four indices showed that spatial clustering existed in the acute cases, which was consistent with the results of spatial moving scan window method. The latter method also found a most likely cluster, the coordinate of the circle center is (30.65 N, 117.44 E), radius is 2.69 km, and relative risk is 12.78 (DIR = 32. 80, P = 0. 0001). CONCLUSION: The quantified indices to describe the distributional status of diseases have not only solved the obstacle that spatial point pattern map which could only be analyzed qualitatively, but also supplied a theoretical foundation to deepen spatial clustering analysis. OBJECTIVE: To study the quantified indices for describing the distributional status of

[Spatial distribution pattern of Oncomelania hupensis population in marshland and lake area].

OBJECTIVE: To explore the spatial pattern of the distribution of Oncomelania hupensis population in marshland and lake region. METHODS: Four bottomlands were selected randomly for the investigation along the Qiupu River in Guichi District, Anhui Province. The quadrats were placed randomly for snail survey, and the mean crowding, mean density, aggregation indices (diffusion coefficient (C), morisita index (Idelta), index of patchiness (m*/m) ), Taylor's power law and Iwao's m*-m regression index were analyzed. RESULTS: For 4 bottomlands in different time, the diffusion coefficients, Morisita indices, and m*/m indices were all more than one. There was a close linear relationship between the logarithm of the snail density and its variance (P < 0.01), and the correlation coefficient was 0.972. In Taylor's power law, the lg a was 0.602 and b was 1.427. There was a close linear relationship between the mean crowding (m*) and the snail density (m) (P < 0.01), and the correlation coefficient, alpha and beta was 0.984, 2.367 and 1.617 respectively. CONCLUSION: The spatial pattern of Oncomelania hupensis population shows an aggregation distribution in marshland and lake region, and the basic components of snail distribution are in colonies.

[Scan statistic method with moving window and its application in the temporal clustering detection of acute schistosomiasis].

Acute schistosomiasis cases from 2001 to 2006 in Guichi District, Chizhou City, Anhui Province, were collected and analyzed by scan statistic method with moving window, central degree approach and circular distribution method in order to detect the temporal clustering of schistosomiasis. The analyzed data provided by the method showed that the temporal clustering of acute schistosomiasis from 2001 to 2003 in Guichi District became more concentrative, and then disperse, resulting in a final disappearance of the clustering in 2006 (LLR = 4.14, P > 0.05). The temporal clustering for all cases in the six years detected by scan statistic method was between August to September in 2002 (LLR = 18.5, P < 0.01), which was consistent with the real condition. Whereas the results from the central degree and the circular distribution methods could only provide limited information and were biased in the analysis in 2002, indicating that the scan statistic method with moving window can provide ample information with more robust and credible results.

[Observation on the change of anti-S. japonicum antibody level in population migrated from outside embankment to new town].

OBJECTIVE: To detect the change of the anti-S. japonicum antibody level after people migrated from outside embankment to newly established town. METHODS: Three pilot spots were established for the investigation: one spot that both inhabitancy and cultivation disuse (A), one spot that only inhabitancy disuse but farming continued (B) and the third one served as control (C). DIGFA and ELISA were used to detect the antibody level in the populations from 2002 to 2005. RESULTS: The positive rate of anti-S. japonicum antibody declined significantly from 6.63% to 3.52% by DIGFA and from 7.26% to 3.71% by ELISA at spot A (chi2=5.2625, P<0.05; chi2=6.3296, P<0.05, respectively). There was no significant difference on the positive rate of antibody in spots B and C. The average A450 value of ELISA in the three spots was statistically analyzed by One-Way ANOVA. It was only in spot B that the average A450 value declined from 0.182 in 2003 to 0.147 in 2005 (P<0.01). CONCLUSION: The anti-S. japonicum antibody level in human population has decreased at certain degree after they migrated from outside embankment to new town.

[Linear models for predicting of Oncomelania hupensis in the lake and marsh regions].

OBJECTIVE: To study the prediction model of O. hupensis in the lake and marshland regions in order to provide methodological basis for quantitative study of O. hupensis. METHODS: The research sites were randomly selected from the bottomlands along Qiupu River in the Guichi District, Anhui Province. A random and stratified sampling method was administrated according to the type of vegetation; the frame size of snail survey was 0.11 m2. Snail data was collected by crosscheck-random sampling inspection survey. Elevation, soil temperature and air temperature, height of vegetation, soil humidity and types of vegetation were measured through GPS machine, T&D Recorder for Windows, tape measure and attemperator. All the data were doubly inputted into the computer and checked. The final dataset for developing the prediction model was set up after necessary data preprocessing, such as, recoding the variable of elevation. The generalized linear models were used to develop the prediction model, and the statistics of deviance and AIC were used to determine the best model structure. Model diagnostics and model evaluation of efficiency were performed with the determined best model structure. RESULTS: The sample size was 162, and there were 6 explanatory variable including 2 categorical variables and 4 quantitative variables. A complicated relationship was observed among all the variables. Snail was positively associated with height of vegetation (r = 0.36), while negatively associated with soil humidity (r = - 0.22), and the air temperature had a close positive relations with soil temperature (r = 0.59), and the soil temperature was negatively associated with height of vegetation (r = - 0.36), the soil humidity had negative relations with the soil and air temperature (r = -0.34 and -0.12). The best structure fitting for the liner model selected in gamma distribution was the error distribution, reciprocal as the conjunction function in mathematics, and the mean square as the variance function. The results showed that the elevation, soil humidity, soil temperature, types and the height of vegetation were statistically significant to predict the O. hupensis, while t-values were -3.202, 3.124, -1.989, 2.668 and -2.371, respectively, and P-values were 0.00166, 0.00214, 0.04849, 0.00846 and 0.01897 respectively. CONCLUSION: The generalized linear models can be used to develop the predictive model, which could broaden the area of quantitative study for O. hupensis.

[Comparison of the burn wound and diabetic ulcer wound].

OBJECTIVE: To compare the difference between the burn wound and diabetic ulcer wound, and to preliminarily analyze the nonhealing mechanism of diabetic unclear. METHODS: The tissue of foot ulcer of diabete patients and skin wound tissues from burn patients were harvested. The levels of (FGF)2 and VEGF in the wound tissues were determined after tissue cultivation with enzyme-linked immunosorbent assay (ELISA). The changes in micro-vascular density (MVD) were examined by immunohistochemistry. Human umbilical vein endothelial cells were cultured in medium containing different components, and divided into following groups: A (with treatment of 5 mmol/L glucose for 7 days), B (with treatment of 30 mmol/L glucose for 7 days) and C (with treatment of 30 mmol/L Mannitol for 7 days) groups, then the level of VEGF protein was determined by ELISA. RESULTS: The levels of FGF2 and VEGF protein in the burn wound were (59 +/- 3) ng/ml and (56 +/- 7) pg/ml, respectively, which were obviously lower than those in diabetic ulcer wound [(89 +/- 6) ng/ml, (108 +/- 5) pg/ml, P < 0.05]. There was also obvious difference in MVD between two kinds of wound (P < 0.05). The level of VEGF protein in both wounds were similar after the addition of FGF2 to the cell culture in vitro, while there were statistically significant difference 2 and 5 days after removal of FGF. CONCLUSION: The nonhealing mechanism of diabetic ulcer wound may be related to the inhibition of vacuolation and low expression of factors controlling vessel growth.

[Effect of Chinese herbs on expression of aquaporin 3,4 gene in gastric mucosa of patients with Pi-Wei Damp-Heat syndrome].

OBJECTIVE: To explore the relationship between Pi-Wei Damp-Heat Syndrome (PWDHS) with expression of aquaporin (AQP) 3,4 gene in gastric mucosa and the effects of Qingre Huashi Recipe (QHR) on the expression. METHODS: Sixty-eight patients with chronic superficial gastritis were differentiated into Pi-Wei Damp-Heat Syndrome group (PWDHS, n = 53, 19 cases with predominant Dampness, 14 cases with predominant Heat, 20 cases with Dampness equal to Heat) and Pi deficiency Syndrome group (PDS, n = 15). The PWDHS were treated with QHR. The expression of AQP 3,4 gene in the two groups were determined by fluorescence quantitative polymerase chain reaction (FQ-PCR). RESULTS: Expression of AQP 3 gene in PWDHS was higher than that in PDS and the healthy group, but the difference showed no statistical significance. Expression of AQP 4 gene in PWDHS was obvious higher than that in PDS and the healthy group (P <0.05 or P <0.01), but the difference of AQP 4 gene expression between PDS and the healthy group was insignificant. Comparison among various sub-types of PWDHS showed that the AQP 4 gene expression in the predominant dampness > dampness equal to heat> predominant heat. AQP 3,4 gene expression in PWDHS was significantly decreased after QHR treatment, especially in the cases with predominant dampness syndrome (P <0.01), approaching that in the healthy group and PDS. CONCLUSION: Abnormal expression of AQP 3,4 gene may be one of the possible mechanisms of PWDHS pathogenesis, Chinese herbs could influence AQP 3,4 gene expression to play a key role in treatment.