痛泻要方对小鼠胃肠运动双向调节作用的研究

目的通过观察痛泻要方对小鼠不同机能状态胃肠运动的影响,研讨痛泻要方对胃肠运动的双向调节作用。方法采用大黄致小鼠腹泻模型、复方地芬诺酯致小鼠便秘模型及正常小鼠,观察不同剂量其对各组排稀便数量、次数、粪便直径及腹泻率、稀便率、稀便级、腹泻指数的影响;并通过对新斯的明致小鼠小肠推进功能亢进、阿托品致小鼠小肠推进功能抑制及正常小鼠小肠推进运动的影响,观察痛泻要方对小鼠小肠推进运动的调节作用。结果痛泻要方对小鼠腹泻模型、新斯的明致小鼠小肠推进功能亢进均有一定抑制胃肠运动作用;对小鼠便秘模型、阿托品致小鼠小肠推进功能抑制均有一定促进胃肠运动作用;对正常小鼠及其小肠推进运动均无明显作用。结论痛泻要方对小鼠不同机能状态胃肠运动有不同影响,具有双向调节作用,与中医方证相符、辨证论治相合。

中药对胃肠动力的调节作用及机制研究

胃肠动力学异常性疾病的发病率日益升高,近年来许多研究发现不少中药有促胃肠动力作用,其调节机制主要涉及到神经调节和脑-肠肽调节,包括胆碱能受体、肾上腺素能受体、胃动素、血管活性肽、生长抑素、P物质等途径。

含铁肠杆菌素受体调节蛋白VPA0148对副溶血弧菌毒力的影响

副溶血弧菌(Vibrio parahaemolyticus)是一种嗜盐性革兰氏阴性菌,广泛分布于海洋环境中,能够引起肠胃炎、伤口感染以及败血症,是人类重要的病原菌之一。宿主体内被认为是一种低铁环境,能够激发致细菌的毒力。副溶血弧菌能够分泌弧菌素或利用外源铁载体来获取铁。在低铁条件下,编码双组份调控系统的基因簇VPA0148-VPA0149转录上调,使含铁肠杆菌素受体PeuA转录出有活性的蛋白。VPA0148编码产物为一个响应调节因子,具有一个磷酸基团接收结构域和一个DNA结合结构域。本研究发现,VPA0148的缺失增强了菌株的生物膜形成能力和对斑马鱼的致死能力,同时能够促进菌株在低铁环境中的生长,并增强菌株的群集运动。研究结果表明含铁肠杆菌素受体调节蛋白VPA0148对副溶血弧菌致病力具有调控作用,增进了对铁调节副溶血弧菌毒力机制的认识。

中医药治疗代谢相关脂肪性肝病的研究进展

目前,代谢相关脂肪性肝病(MAFLD)仍缺乏针对性治疗药物,而中医药治疗具有良好的应用前景。本文从中医内治、外治相结合,并配合子午流注经络疗法、运动联合脊柱骨盆修复、肠肝调节等方面阐述中医药治疗MAFLD的研究进展。

Effect of Echinacea purpurea Polysaccharide on IL-6 m RNA Expression Level in IEC-6 Cell after LPS Injury

[Objective] The aim was to investigate the effect of Echinacea purpurea polysaccharide （EPS） on IL-6 mRNA expression level in IEC-6 cell after lipopolysac- charide （LPS） injury. [Method] Total RNA of IEC-6 cell was extracted with TRIzon reagent and amplified by R-r-PCR. The amplification products were examined by a- garose gel electrophoresis and graphed for analysis. [Result] After stimulation by LPS, the IL-6 mRNA expression level in iEC-6 cell increased. However, EPS could inhibit this effect, and the inhibitory effect was dose-dependent. At the concentration of 50 μg/ml, EPS could partially inhibit the IL-6 mRNA expression in IEC-6 cell after LPS stimulation; in the concentration range of 100-500 μg/ml, the inhibitory effect of EPS on IL-6 mRNA expression in iEC-6 cell increased with the increase of con- centration. When the IEC-6 cell was pre-treated with EPS （50, 100, 200 and 500 μg/ml） for 24 h and then stimulated with LPS （10 μg/ml） for 1 and 4 h, respectively, it was found that the LPS-induced mRNA expression of IL-6 in IEC-6 cell was in- hibited by EPS, and this kind of inhibitory effect was time-dependent. [Conclusion] After small intestinal epithelial cells were stimulated by LPS, the IL-6 mRNA expres- sion level increased. However, EPS could inhibit the LPS-induced mRNA expression of IL-6, thus protecting the intestinal mucosa. In addition, this kind of inhibitory effect showed time and concentration dependence.

Effects of four regulating-intestine prescriptions on pathology and ultrastructure of colon tissue in rats with ulcerative colitis

AIM: To observe different histomorphologic changes of ulcerative colitis (UC) rats that were treated with four regulating-intestine prescriptions (FRIP), to investigate the curative effects of FRIP and to analyze their treatment mechanism.METHODS: The UC rat model was made by the method of 2,4-dinitro chloro benzene (DNCB) immunity and acetic acid local enema. Ninety-eight SD rats were randomly divided into seven groups, namely, the normal control group, model group, salicylazosulfapyridine (SASP) group,Wumeiwan (WMW) group, Baitouwengtang (BTWT) group,Senglingbaishusan (SLBSS) group, and Tongxieyaofang (TXYF) group. Each group had 14 rats (with equal ratio of male and female). The six animal model groups of UC-SASP, TXYF, WMW, BTWT, SLBSS, TXYF-were treated by distilled water except the normal control group. Changes of the rat's general conditions after treatment were respectively observed, the colon tissue damage scores were given out, the pathology of colonic mucosa and changes of ultrastructure were analyzed.RESULTS: Different pathological changes on histology were shown after treatment by FRIP. The colon tissue damage score in model group was higher than that of FRIP groups and SASP group (q = 4.59, 4.77, P＜0.05 or q = 5.48,6.25, 5.97, P＜0.01). The scores of WMW group, BTWT group and SLBSS group were lower than that of SASP (q = 4.13, P＜0.05 or q = 5.31, 5.12, P＜0.01). There was no remarkable difference between the damage score of TXYF group and SASP group (q = 3.75, P＞0.05). In addition, some apoptosis cells were found in the pathologic control group.CONCLUSION: The model made with DNCB and acetic acid was successful, and FRIP had better curative effect and WMW was the best curative effect, BTW, SLBSS and TXYF were similar to SASP, and we discovered that apoptosis was possibly related to UC.

B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma

AIM： To investigate the expression of B7-H1 in human colorectal carcinoma （CRC） to define its regulating ef- fects on T cells in tumor microenvironment.

Application of dietary fiber in clinical enteral nutrition: A meta-analysis of randomized controlled trials

AIM: To evaluate the effects of dietary fiber (DF) as a part of enteral nutrition (EN) formula on diarrhea, infection, and length of hospital stay. METHODS: Following electronic databases were searched for randomized controlled trials about DF: Chinese Biomedicine Database (CBM), MEDLINE, EMBASE and Cochrane Controlled Trials Register. RevMan 4.1 was used for statistical analysis. RESULTS: Seven randomized controlled trials with 400 pat-ients were included. The supplement of DF in EN was compared with standard enteral formula in five trials. Combined analysis did not show a significant reduction in occurrence of diarrhea, but there were valuable results for non-critically ill patients. Combined analysis of two trials observing the infection also did not show any valid evidence that DF could decrease the infection rate, though the length of hospital stay was reduced significantly. CONCLUSION: Based on the current eligible randomized controlled trials, there is no evidence that the value of DF in the diarrhea can be proved. Though length of hospital stay was shortened by the use of DF, there is no available evidence in preventing infection by DF. Further studies are needed for evaluating the value of DF in EN.

T-regulatory lymphocytes in peripheral blood of gastric and colorectal cancer patients

AIM: To assess the absolute number of T-regulatory cells (Tregs; CD4+CD25+Foxp3+) in the peripheral blood of gastric and colorectal cancer patients. METHODS: We enrolled 70 cancer patients (33 gastric cancer, 37 colorectal cancer) and 17 healthy volunteers. The CD3+CD4+ lymphocytes and CD4+CD25+Foxp3+ Tregs in the peripheral blood were analyzed with flow cytometry. The absolute numbers of Tregs were calculated based on the CD4+CD25+Foxp3+ cells percent-age of CD3+CD4+ cells and the absolute numbers of CD3+CD4+ cells per microliter. RESULTS: The mean number of CD4+CD25+Foxp3+ cells per microliter in colorectal cancer patients was 15.7 (SD: 21.8), for gastric cancer patients 12.2 (SD: 14.3), and for controls 17.5 (SD: 11.4). The absolute number of Tregs was significantly lower in gastric cancer patients than in controls (P = 0.026). There was no statistically significant difference for gastric vs colorectal cancer or colorectal cancer vs controls. The absolute number of Tregs was also significantly depressed in N+ vs Ncancer patients [22.0 (27.7) vs 10.1 (9.0), P = 0.013], and in the subgroup of gastric cancer patients [30.3 (27.6) vs 9.6 (8.0), P = 0.003]. No statistical difference was observed in the proportion of Tregs in the CD4+ population between the groups. CONCLUSION: The absolute number of Tregs in peripheral blood of gastric cancer but not colorectal cancer patients was significantly decreased in comparison with that in healthy controls.

A framework for the modeling of gut blood flow regulation and postprandial hyperaemia

After a meal the activity of the gut increases markedly as digestion takes place. Associated with this increase in activity is an increase in blood flow, which has been shown to be dependent on factors such as caloric content and constitution of the meal. Much qualitative work has been carried out regarding mechanisms for the presence of food in a section of gut producing increased blood flow to that section, but there are still many aspects of this process that are not fully understood. In this paper we briefly review current knowledge on several relevant areas relating to gut blood flow, focusing on quantitative data where available and highlighting areas where further research is needed. We then present new data on the effect of feeding on flow in the superior mesenteric artery. Finally, we describe a framework for combining this data to produce a single model describing the mechanisms involved in postprandial hyperaemia. For a section of the model, where appropriate data are available, preliminary results are presented.

Modulation of Gut Microbiota in Pathological States

The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract （GIT）. Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease （NAFLD）; obesity and diabetes, which are characterized as ＂lifestyle diseases＂ of the industrial- ized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the read- er with an updated overview of the importance of the gut microbiota for human health and the poten- tial to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile （C difficile） infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial mi- crobes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.

Analysis of the characteristics of gastrointestinal motility based on Hilbert-Huang transform method

Pressure activity data as an important index of gastrointestinal （GI） motility can be obtained from the wireless radiotelemetry capsule. The Hilbert-Huang transform （HHT） method, which is more effective to process non-stationary signal, is proposed to identify the characteristics of GI motility. We decompose the pressure activity data into intrinsic mode functions （IMFs）, calculate the Hi/bert marginal spectrum and attain the peristalsis characteristics of GI tract. The IMFs represent the peristalses modes of GI tract activity embedded in the pressure data. The time-varying characteristic of the method suggests that the HHT is suitable to accommodate other non-stationary biomedical data analysis.

Correlation between clinicopathology and expression of heat shock protein 70 and glucose-regulated protein 94 in human colonic adenocarcinoma

AIM: To investigate the correlation between clinicopathology and expression of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human colonic carcinoma. METHODS: The expression of HSP70 and grp94 was studied in 80 human colonic cancers with or without metastasis as well as in their adjacent mucous membrane by way of immunohistochemistry and pathology photograph analysis. RESULTS: The expression of HSP70 and grp94 was significantly higher in cancer than that in adjacent mucous membrane (92.5%, 85.0% vs 56.3%, 42.5%, P<0.01). HSP70 and grp94 expressed higher in moderately- and poorly-differentiated colonic cancers than that in their adjacent tissues (93.7%, 87.5%; 100%, 90% vs56.3%, 42.5%;P<0.01). Dukes C and D stages of colonic cancers showed higher positive rates than Dukes A and B stage groups (97.1%, 91.2%; 100%, 90.9%; vs 80%, 70%; 78.6%, 71.4%; P<0.05). There were definite differences in HSP70 and grp94 expression between metastasis groups and non-metastasis groups (100% vs 75%, 100% CONCLUSION: The HSP70 and grp94 expression rates in colonic cancer groups are significantly higher than that in their adjacent mucous membrane. The HSP70 and grp94 expression in poorly-differentiated colonic cancers with metastasis is significantly higher than well-differentiated cancers without metastasis. The overexpression of HSP70 and grp94 can be used as diagnostic or prognostic markers for colonic cancer.

Use of the tumor necrosis factor-blockers for Crohn's disease

The use of anti-tumor necrosis factor-α therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn＇s disease study thirty years ago. The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses. In general, it is suggested that tumor necrosis factor-c~ blockers （TNFBs） are indicated （1） for persons with moderately-severe Crohn＇s disease or ulcerative colitis （UC） who have failed two or more causes of glucocorticosteroids and an acceptably long cause （8 wk to 12 wk） of an immune modulator such as azathioprine or methotrexate; （2） non-responsive perianal disease; and （3） severe UC not responding to a 3-d to 5-d course of steroids. Once TNFBs have been introduced and the patient is responsive, therapy given by the IV and SC rate must be continued. It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance ther- apy, and when or if TNFB may be weaned and discon- tinued. The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient＇s illness needs to be confirmed. The risk/benefit profile of TNFB appears to be accept- able as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB, and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic. Because the rates of ben- efits to TNFB are modest from a population perspec- tive and the cost of therapy is very high, the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

Adenosine:An immune modulator of inflammatory bowel diseases

Inflammatory bowel disease(IBD)is a common and lifelong disabling gastrointestinal disease.Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response.Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models.High extracellular adenosine suppresses and resolves chronic inflammation in IBD models.High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis.Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells,respectively. Increased extracellular adenosine levels activate the A2a receptor,which would reduce cytokines responsible for chronic inflammation.

Bifidobacterium lactis attenuates onset of inflammation in a murine model of colitis

AIM: To assess the anti-inflammatory effect of the probiotic Bifidobacterium lactis (B. lactis) in an adoptive transfer model of colitis. METHODS: Donor and recipient mice received either B. lactis or bacterial culture medium as control (deMan Rogosa Sharpe) in drinking water for one week prior to transfer of a mix of naive and regulatory T cells until sacrifice. RESULTS: All recipient mice developed signs of colonic inflammation, but a significant reduction of weight loss was observed in B. lactis-fed recipient mice compared to control mice. Moreover, a trend toward a diminution of mucosal thickness and attenuated epithelial damage was revealed. Colonic expression of pro-inflammatory and T cell markers was significantly reduced in B. lactis-fed recipient mice compared to controls. Concomitantly, forkhead box protein 3, a marker of regulatory T cells, was significantly up-regulated by B. lactis. CONCLUSION: Daily oral administration of B. lactis was able to reduce inflammatory and T cells mediators and to promote regulatory T cells specific markers in a mouse model of colitis.

Role of the duodenum in regulation of plasma ghrelin levels and body mass index after subtotal gastrectomy

AIM: To investigate the role of the duodenum in the regulation of plasma ghrelin levels and body mass index (BMI), and the correlation between them after subtotal gastrectomy. METHODS: Forty-two patients with T0-1N0-1M0 gastric cancer were divided into two groups after gastrectomy according to digestive reconstruction pattern, Billroth Ⅰ group (n = 23) and Billroth Ⅱ group (n = 19). Ghrelin levels were determined with radioimmunoassay (RIA) before and on d 1, 7, 30 and 360 after gastrectomy, and BMI was also measured. RESULTS: The two groups had identical postoperative trends in ghrelin alterations during the early stage, both decreasing sharply to a nadir on d 1 (36.7% vs 35.7%), then markedly increasing on d 7 (51.0% vs 51.1%). On d 30, ghrelin levels in the Billroth Ⅰ group were slightly higher than those in the Billroth Ⅱ group. However, those of the Billroth Ⅰ group recovered to 93.6% on d 360, which approached, although lower than, the preoperative levels, and no statistically significant difference was observed. Those of the Billroth Ⅱ group recovered to only 81.6% and manifested significant discrepancy with preoperative levels (P = 0.033). Compared with preoperative levels, ghrelin levels of the two groups decreased by 6.9% and 18.4% and BMI fellby 3.3% and 6.4%, respectively. The linear regression correlations were revealed in both groups between decrease of ghrelin level and BMI (R12 = 0.297, P = 0.007; R22 = 0.559, P < 0.001).CONCLUSION: Anatomically and physiologically, the duodenum compensatively promotes ghrelin recovery and accordingly enhances BMI after gastrectomy. Regarding patients with insufficient ghrelin secretion, ghrelin is positively associated with BMI.

Munc18/SNARE proteins’ regulation of exocytosis in guinea pig duodenal Brunner’s gland acini

AIM: To examine the molecular mechanism of exocytosis in the Brunner’s gland acinar cell. METHODS: We used a submucosal preparation of guinea pig duodenal Brunner’s gland acini to visualize the dilation of the ductal lumen in response to cholinergic stimulus. We correlated this to electron microscopy to determine the extent of exocytosis of the mucin-filled vesicles. We then examined the behavior of SNARE and interacting Munc18 proteins by confocal microscopy. RESULTS: One and 6 μmol/L carbachol evoked a dose- dependent dilation of Brunner’s gland acini lumen, which correlated to the massive exocytosis of mucin. Munc18c and its cognate SNARE proteins Syntaxin-4 and SNAP-23 were localized to the apical plasma membrane, and upon cholinergic stimulation, Munc18c was displaced into the cytosol leaving Syntaxin-4 and SNAP-23 intact. CONCLUSION: Physiologic cholinergic stimulation induces Munc18c displacement from the Brunner’s gland acinar apical plasma membrane, which enables apical membrane Syntaxin-4 and SNAP-23 to form a SNARE complex with mucin-filled vesicle SNARE proteins to affect exocytosis.