Volume 85  ·   Issue 39  ·  2005

The National Academic Conference on Clinical and Basic Research of Gastrointestinal Mucosal Barrier was held in Beijing from May 28 to 30, 2005. It was the first academic conference on gastrointestinal mucosal barrier in China, with more than 400 participants. The main content of the conference was the basic and clinical research on gastrointestinal mucosal barrier, as well as the research progress of micro-ecological preparations and enteral nutrition. In recent years, some achievements have been made in the research of gastrointestinal mucosal barrier in China, but there are still some problems, which should be paid attention to.

Dysbacteriosis is a common clinical syndrome, but its detection methods have always troubled clinical examiners. From the current detection methods, there are four kinds of methods, namely, direct smear method, plate live bacteria counting method, 16SrRNA gene probe method and its biochip method.

When the gastric mucosa is attacked by various pathogenic factors and the gastric mucosal barrier is destroyed, mucosal inflammatory damage occurs immediately. It is generally believed that superficial mucosal damage causes superficial or erosive gastritis; If the damage is severe or inflammatory stimulation persists, it will lead to deep mucosal damage, and if it cannot be repaired, it may lead to atrophic gastritis or gastric ulcer.Of course, the body will undergo cell adaptation at the same time of damage.Through the proliferation and migration of epithelial cells around the injury, the epithelial tissue and mucosal glands can be repaired and regenerated.This process is called mucosal repair and reconstruction.When mucosa cannot be completely repaired, metaplasia will occur, and intestinal epithelial metaplasia is the result of incomplete repair (metaplasia) after deep gastric mucosal injury. The gastric mucosal repair process is regulated by growth factors and their receptors.Growth factors are a group of peptides or protein hormones including epidermal growth factor (EGF) and transforming growth factor (TGF), which can promote the regeneration of injured mucosal cells, gland and tissue repair, increase mucosal blood flow, etc., and play a vital role in complete repair after gastric mucosal injury.

The intestinal barrier changes in cirrhosis, especially when ascites and bacteria translocation (BT) are combined, the intestinal permeability increases significantly, and there are obvious changes earlier than the morphology of intestinal mucosa [1, 2]. In patients with cirrhosis, the interstitial space of intestinal epithelial cells in distal duodenum is widened by tightly connected, and the ultrastructural abnormalities such as shortening and thickening of microvilli [3] lead to the change of mechanical barrier. The pH in the intestinal mucosa decreased and the pH in the intestinal lumen increased; The deficiency of bile salts in the intestinal lumen caused the change of chemical barrier.Colonic bacteria, especially aerobic bacteria such as Escherichia coli and Proteus and anaerobic pathogenic bacteria such as Clostridium, increased significantly in patients with liver cirrhosis, while the number of predominant anaerobic bacteria in normal colon, such as bifidobacterium, eubacterium and bacteroidetes, decreased significantly. The concentration of secreted IgA (sIgA) in the intestinal contents of cirrhosis rats decreased significantly, the number of CD +4 and CD +8 T cells in the lamina propria of intestinal mucosal epithelium decreased significantly, and the ratio of CD +4/CD +8 decreased significantly [4].

The integrity of gastric mucosa and normal gastrointestinal motility are two basic conditions for maintaining gastric physiological functions. Among them, the integrity of gastric mucosa is indispensable for maintaining gastrointestinal tract function including gastric motility, and the normal gastric motility is beneficial to remove harmful substances and maintain the balance of local microenvironment, so as to protect gastric mucosa. Many studies have shown that mucosal injury and motility dysregulation play an important role in the pathogenesis of many gastrointestinal diseases [1], and the two are interrelated and influence each other.

Objective to investigate the inhibitory effect of esophageal cancer related gene 2 (ECRG2) on the malignant proliferation of EC9706 esophageal carcinoma cells and its mechanism.Methods the eukaryotic expression plasmid of ECRG2 (pcDNA3.1-ECRG2) was constructed by DNA recombination technique.The expression of ECRG2 protein was transfected in EC9706 esophageal carcinoma cells and the growth status of EC9706 cells was observed. The change of plate colony and soft agar clone formation ability was compared, and the effect of ECRG2 on the malignant phenotype of EC9706 cells was analyzed. The changes of p53 and p21 were further detected by Western Blot. Results After transfection and expression of ECRG2, the growth of EC9706 cells was interfered and the cell proliferation rate was inhibited. The plate colony formation rate was 18% in the experimental group and 55% in the control group, and the difference between the two cells was significant (P<0.05); The mooring-independent ability of tumor cells was decreased, and the number of soft agar clones in the experimental group (8±1.88) was significantly less than that in the control group (14.3±3.13), and the difference was significant (P<0.05). Western Blot analysis showed that the expression of p53 and p21 protein increased after EC9706 cells were transfected with ECRG2. Conclusion ECRG2 protein transfection can partially reverse the malignant phenotype of EC8706 cells, and the process may be closely related to p53 and p21 pathways.

Objective to investigate whether mesenchymal stem cells (MSCs) derived from adult proximal femur have immunosuppressive function and to find an ideal cell reserve for the prevention and treatment of graft versus host disease. Methods MSCs were isolated and cultured from the proximal femur of patients undergoing total hip arthroplasty. Different numbers of MSCs were added to mixed lymphocyte reaction (MLR) directly or by Transwell method to detect the effects of MSCs on the proliferation of peripheral blood lymphocytes (PBL). The effects of cytokine TGF-β 1 on the immunoregulation of MSCs were investigated by ELISA and antibody neutralization method.Results The inhibitory rates of 3×103, 1×104, 3×104 and 1×105 MSCs derived from proximal femur on PBL proliferation were 62% ± 18%, 38% ± 4%, 31% ± 16% and 28% ± 12%, respectively. There was no significant difference between the inhibitory effects of MSCs derived from iliac bone marrow puncture (all P>0.05). The inhibitory rates of the latter on PBL proliferation were 58%±12%, 37%±8%, 28%±6% and 27%±6%. The proliferation inhibition rate of 3×104 and 1×104 MSCs on PBL was 36%±8% and 53%±12% when the MSCs were separated from MLR by 0.2 μ m microporous membrane. In ELISA, the expression levels of transforming growth factor (TGF) -β 1 in these three supernatants were not statistically significant when MSC was cultured alone, MSC was directly contacted with MLR, or co-cultured by Transwell. Increasing concentration of TGF-β 1 antibody could not reverse the inhibitory effect of MSC on PBL proliferation. Conclusion MSC originating from proximal femur has certain immunosuppressive function, and other soluble factors besides TGF-β 1 may mediate this effect.

Objective to study the normal shape and structure of the main white matter fibrous bundles and the abnormal changes caused by intracranial tumors by magnetic resonance diffusion TENSOR fibrography.Methods diffusion TENSOR imaging was performed in 10 normal volunteers (5 males and 5 females, aged 24-65 years, mean 40.9 years) and 28 patients with intracranial tumors (9 males and 19 females, aged 11-77 years, mean 43.0 years), respectively.The data obtained were entered into personal computer.The software Volume-one1.56 and diffusion TENSOR Visualizer 1.5 (dTV) developed by the Imaging Computation and Analysis Laboratory of the Department of Radiology, Affiliated Hospital of Tokyo University, Japan were used to perform the imaging of the main white matter fibrous bundles in vivo. The projection fibers mainly show the corticospinal tract; The abnormal changes of white matter fibrous bundles involved in intracranial tumors include arcuate fiber, superior longitudinal bundle, inferior longitudinal bundle, cingulate bundle, corticospinal bundle, external capsule, optical radiation and corpus callosum. The abnormal changes of white matter fibrous bundles can be divided into four types: destruction + infiltration in 7 cases, destruction + displacement in 10 cases, infiltration + displacement in 3 cases and displacement in 8 cases. Conclusion Diffusion tensor fibrous bundle imaging can show the abnormal changes of white matter fibrous bundles caused by normal brain and intracranial tumors.

Objective to investigate the etiology, diagnosis and treatment of multiple segmental intestinal agangliocytosis. Methods Three children, aged 5 d, 29 d, 18 months, were retrospectively analyzed in our hospital from 1987 to 2005. Pathological examination was performed by HE staining. Total colectomy, ileal prolapse and radical Hirschsprung's colonectomy were performed. Results All three children were diagnosed with Hirschsprung's colon before operation. During the operation, stenosis of terminal ileum and initial segment of ascending colon was explored. Pathological section confirmed that there were no ganglion cells in the intestinal wall of stenosis. Conclusion Children with long segment Hirschsprung's colon should explore the whole colon and ileum to avoid missed diagnosis. The pathogenesis of Hirschsprung's disease is caused not only by the pause of embryonic development during the migration of neuroblasts from the neural crest to the intestinal tube in the early embryonic stage, but also by the development disorder of ganglion cells in different segments during the maturation of ganglion cells.

Objective to evaluate the safety and efficacy of interventional technique in the treatment of early hepatic artery thrombosis (HAT) after orthotopic liver transplantation (OLT). Methods Nine patients with early HAT after OLT were treated with interventional therapy. 8 males and 1 female, aged 32-63 years (mean 47.6 years). All 9 cases showed progressive increase of transaminase and bilirubin after operation. HAT occurred from 16 h to 10 d (mean 5 d) after transplantation, and ultrasonography showed that HAT was confirmed by angiography. The interventional therapy methods included continuous low-dose thrombolysis with indwelling catheter in the hepatic artery and stenting in the hepatic artery, and low-dose heparin intravenously. Ultrasound was repeated at 12 h intervals during the period of thrombolysis in the hepatic artery. Results Thrombolysis was successful in 7 cases, accounting for 78% (7/9). The repeated angiography showed that blood flow passed through the hepatic artery and the branches of the intrahepatic artery were visualized, and the liver function was significantly improved. The time of indwelling catheter in the hepatic artery was 12 h to 9 d (mean 4.8 d). Seven patients with successful thrombolysis had different degrees of hepatic artery anastomosis stenosis, 6 of them had stenosis degree>90%, and endovascular stenting was performed in the area of hepatic artery stenosis. Two patients failed thrombolysis therapy. One patient had intraabdominal hemorrhage 12 h after the start of thrombolysis. Emergency laparotomy was performed, and hemorrhage of hepatic artery anastomosis was found, and then reanastomosis was performed. One patient failed to open the hepatic artery occlusion after 7 days of thrombolysis with indwelling catheter, but the collateral branches of blood supply to the liver were established, and the liver function was improved, and no further treatment was performed. Seven patients with successful therapy were followed up for 2~14 months (median 6 months), and their general condition was good, and the reexamination of ultrasound showed that the blood flow of hepatic artery was unobstructed.Conclusion Transcatheter endovascular intervention is an effective method for the treatment of early HAT after OLT, and it has high safety.

Objective to investigate the incidence, clinical characteristics and treatment status of atherosclerotic renal artery stenosis (ARAS). Methods to analyze the prevalence, clinical characteristics, treatment mode and prognosis of 87 ARAS patients in 144 patients with renal artery stenosis confirmed by renal arteriography in Peking University First Hospital from 1979 to 2003, and compare them with those of other causes. Results ARAS accounted for 60.4% of the causes of renal artery stenosis, 28.9% and 71.7% of the causes of renal artery stenosis in 1979-1990 and 1991-2003, respectively. Hypertension was observed in 93.1% of ARAS patients, and 37.9% had recent hypertension progression. The proportion of renal insufficiency in ARAS patients with stenosis degree of 50% ~74% was 11.2%, and the proportion of renal insufficiency in ARAS patients with stenosis degree ≥75% was 35.8%, which were higher than those in patients with renal artery stenosis with other causes of the same stenosis degree (all P<The control rate of hypertension and the effective rate of renal function in ARAS patients increased from 54.5% and 63.6% before 1990 to 83.9% and 85.5% after 1990, respectively. There was no significant difference between the effective rate of hypertension control and the effective rate of renal function in ARAS patients with the same degree of stenosis and the same level of serum creatinine.

Objective to investigate the role of Helicobacter pylori (Hp) in the development of gastric carcinoma. Methods Cluster random sampling method was used to select 14 natural villages in Linqu County, Shandong Province. Gastroscopy and serological examination were performed on natural people aged 35-64 years. Gastric mucosal biopsy tissues were taken for pathological diagnosis, and Hp antibody was detected by enzyme-linked immunosorbent assay. After 5 and 10 years of follow-up, gastroscopy was performed again in this population. During the follow-up period, both natural occurrence and gastroscopy cases were registered. Results After 10 years of follow-up, a total of 2469 subjects were obtained. During the follow-up period, 58 patients developed gastric cancer, 44 cases (2.74%) of 1603 patients with Hp positive infection and 14 cases (1.62%) of 866 patients with Hp negative infection. The risk of gastric cancer in patients with Hp positive infection was significantly higher than that in patients with Hp negative infection [odds ratio (OR) =1.871, 95% confidence interval (CI): There was no significant difference in the progress of transformation to precancerous lesions of gastric cancer between positive and negative patients with Hp infection in normal or superficial gastritis (SG) group (P>0.05). However, the progress of precancerous lesions of gastric cancer in positive patients with Hp infection in atrophic gastritis (CAG) group at baseline was significantly faster than that in negative patients (P<0.01); Moreover, the incidence of gastric cancer in Hp-positive patients (7/615) was significantly higher than that in Hp-negative patients (0/470, P =0.019). After 10 years of follow-up, although the gastric mucosal lesions in Hp-positive patients in baseline intestinal metaplasia (IM) and dysplasia (DYS) groups were more severe than those in negative patients (P<0.05, P<0.01), but the incidence of gastric cancer in both groups was very close: 17/573 and 7/224 in IM group (P =0.907); In DYS group, HP was 19/368 and 7/122 (P =0.806). Conclusion HP is an important promoting factor in the transformation and progression of atrophic gastritis to higher grade precancerous lesions during the formation of gastric cancer, and it has a promoting role in the whole development of precancerous lesions of gastric cancer. HP may not directly cause gastric cancer, but it acts together with other carcinogenic factors to promote the occurrence of gastric cancer. HP may not have important effect on the gastric mucosa of normal or superficial gastritis, and further research is needed.

Objective to investigate the drug resistance of Helicobacter pylori (Hp) to metronidazole, clarithromycin and amoxicillin in Beijing and their changing trends. Methods the gastric antrum mucosal tissues were obtained from 159 patients with upper gastrointestinal symptoms from gastroscopy room, and the clinical isolates of Hp were obtained by microaerobic culture. The minimum inhibitory concentration (MIC) of Hp to metronidazole, clarithromycin and amoxicillin was determined by E-test. Results the drug resistance rates of Hp to metronidazole and clarithromycin in Beijing were 36.0% (18/50) and 10.0% (5/50) from 1999 to 2000, 43.1% (47/109) and 18.3% (20/109) from 2001 to 2002, respectively. The mixed drug resistance rates of metronidazole and clarithromycin were 10.0% (5/50) from 1999 to 2000 and 14.7% (16/109) from 2001 to 2002, and only one strain (1/49) was found. Conclusion The drug resistance rate of Hp to metronidazole in Beijing is high and increasing year by year, and the drug resistant strains and mixed drug resistant strains to clarithromycin are also more common

Methods Fifty male SD rats were randomly divided into blank group, experimental control group, low-dose teprenone group, medium-dose teprenone group and high-dose teprenone group, 10 rats in each group. The rat model of gastric mucosal injury was prepared by subcutaneous injection of prednisolone. The doses of teprenone in the low-, medium-and high-dose groups were 50, 100 and 200mg/kg, respectively, once a day for 7 days. The pathological changes of gastric mucosa were observed, and the ulcer index and histological injury index of gastric mucosa were calculated. The levels of plasma endothelin-1 and prostaglandin E2 (PGE2) in gastric mucosa were detected by radioimmunoassay, and the serum NO content was detected by Griess assay. Results Steroid hormones could cause significant hemorrhagic injury of gastric mucosa. The median ulcer index and histological injury index of rats in the experimental control group were 44.5 and 5.5, which were significantly higher than those in the blank group (all were 0, all P<0.01); The plasma endothelin-1 level of rats in the experimental group was 399 pg/ml ± 74 pg/ml, which was higher than that in the blank group (279 pg/ml ± 56 pg/ml, P<0.01); The plasma NO level (27 μ mol/L±5 μ mol/L) was lower than that in the blank group (36 μ mol/L±5 μ mol/L, P<0.01); The level of PGE2 in gastric mucosa (154 pg/mg ± 83 pg/mg) was lower than that in the blank group (337 pg/mg ± 112 pg/mg, P<0.01). The median ulcer indexes in the low, medium and high dose teprenone groups were 32.5, 23.0 and 23.0, respectively, which were significantly lower than those in the experimental group (all P<0.01). The median histological injury indices were 3.0, 3.0 and 1.5, respectively, which were significantly lower than those in the experimental group (all P<0.01), and the levels of endothelin-1 were 299pg/ml±99 pg/ml,284pg/ml±85 pg/ml,189pg/ml±32 pg/ml,respectively, which were significantly lower than those in the experimental control group (P<0.05,P<0.01,P<0.01); The levels of NO were 56 μ mol/L ± 16 μ mol/L, 62 μ mol/L ± 12 μ mol/L and 83 μ mol/L ± 9 μ mol/L, respectively, which were significantly higher than those of the experimental control group (all P<0.01). The levels of PGE2 in gastric mucosa in the high dose teprenone group were 241pg/mg ± 65 pg/mg, which was significantly higher than that in the experimental group (154pg/mg ± 83 pg/mg) (P<0.05). Ulcer index, histological injury index and endothelin-1 levels decreased with the increase of teprenone dose, while serum NO and PGE2 levels in gastric mucosa increased with the increase of teprenone dose. Conclusion Teprenone has a certain protective effect on steroid-induced gastric mucosa injury, and its mechanism may be related to the decrease of endothelin-1 level and the increase of NO and PGE2 production.

Autologous immune cell therapy is one of the important methods of tumor biotherapy. Under the action of various immune active factors, in vitro culture can eliminate the immunosuppressive factors in tumor patients, activate and expand immune active cells effectively, and directly kill or induce immune effector cells to kill tumor cells after reinfusion in vivo. In recent years, several new autoimmune cell therapies have been developed and established for the treatment of malignant tumors based on the early established autoimmune cell therapies such as lymphokine activated killer cells (LAK) and tumor infiltrating lymphocytes (TIL).

I. Concept of microecological system Biological components such as gastrointestinal native bacteria, foreign bacteria and their epithelial cells, food-borne abiotic components (undigested food) and secretions from stomach, intestines, pancreas and liver (such as hormones, enzymes, mucus, bile salts, etc.) together constitute the microecological system. Any abnormality in one link can cause imbalance of microecological balance, leading to clinical symptoms such as diarrhea and loss of appetite. In addition, improper application of antibiotics will make intestinal flora abnormal, resulting in the reproduction of pathogenic bacteria. Animals' mental state, physiological and immune status and environmental changes will affect the function and secretion composition of gastrointestinal epithelial cells. Microecological imbalance includes two categories: imbalance of flora proportion and localization transfer (translocation). Flora imbalance, that is, imbalance of flora proportion, refers to the qualitative or quantitative change of intestinal native bacteria (probiotics), the total number of probiotic bacteria decreases, and the ratio of probiotics to pathogenic bacteria changes significantly. Localization transfer is also called translocation, Localized metastasis can be divided into lateral metastasis and longitudinal metastasis. Lateral metastasis is transferred from the original location to the periphery, such as lower gastrointestinal bacteria transferring to the upper gastrointestinal tract and colonic bacteria transferring to the small intestine, resulting in small intestine contamination syndrome; Longitudinal metastasis refers to the transfer of bacteria from in situ to the deep intestinal mucosa and even to the whole body [1].

The rapid development of molecular biology technology makes it possible to perform prenatal screening and prenatal diagnosis for a large number of genetic diseases and gene mutations. Early prenatal genetic diagnosis is a hot topic in the field of obstetrics at home and abroad. The arrival of molecular genetic age has brought about many new ethical and social problems, and it is urgent to develop a new model of screening and diagnosis of genetic diseases.

With the deepening of basic medical research, people gradually realize that the intestinal mucosa not only has digestion and absorption functions, but also has important defensive barrier functions. The intestinal tract is the largest contact surface between human body and the external environment, and there are a large number of bacteria and toxins in the intestinal lumen, but under normal circumstances, people do not develop serious infection or toxic diseases. This is mainly because the intestinal mucosa barrier effectively blocks the invasion of foreign microorganisms and toxins, and ensures the health of the body. However, under various stresses or when the intestinal mucosa is locally damaged, this barrier function is weakened, and the pathogenic microorganisms and toxins existing in the intestinal lumen can cross the intestinal barrier, enter the lymphatic system and blood circulation, and bacterial translocation occurs, causing bacteremia or toxemia, and even inflammatory cascade, resulting in multiple organ dysfunction.

non-steroid anti-inflammatory drugs (NSAIDs) based on aspirin are a group of substances with common anti-inflammatory, analgesic and antipyretic effects but different chemical structures. They are one of the most common prescribed drugs. However, these drugs may cause a series of gastrointestinal side effects such as nausea, acid reflux, heartburn, dyspepsia, general ulcer symptoms, and severe bleeding and perforated ulcer in severe cases. They are the second cause of peptic ulcer and upper gastrointestinal bleeding after Helicobacter pylori infection.

mixed epithelial and stromal tumor of the kidney (MESTK) is a rare benign renal tumor, which mostly occurs in adult females. Because its shape resembles infantile congenital mesodermal nephroma, it has long been considered to be an adult tumor with similar properties to infantile congenital mesodermal nephroma, which is called adult mesodermal nephroma.Recently, some authors believe that this disease lacks fundamental connection with infantile mesodermal nephroma, and should be an independent type of renal tumor, and abandon the diagnosis of "adult mesodermal nephroma" and name it "mixed epithelial and stromal tumor of the kidney". This disease is a rare disease. So far, only 41 cases have been reported abroad [1-3] and only 2 cases have been reported in China [4, 5]. We report 2 cases here, and review the literature, and analyze and summarize their clinical and pathological characteristics, diagnosis and differential diagnosis points as follows.

spontaneous bacterial peritonitis (SBP) is a serious complication of liver cirrhosis, and the incidence rate of bacterial peritonitis in decompensated liver cirrhosis is 20% according to domestic reports [1]. spontaneous bacterial peritonitis in liver cirrhosis has a sinister prognosis and is one of the important causes of death in liver cirrhosis. Therefore, early, active and rapid control of inflammation is an important principle for the treatment of SBP. In recent years, our hospital has combined the application of micro-ecological regulators Zhengchangsheng and Peifeikang capsules to prevent and treat SBP on the basis of sufficient antibiotics, and achieved satisfactory clinical efficacy. The summary report is as follows.

The related health problems caused by obesity have placed a heavy burden on the global medical system. Gastric water balloon is a newly developed non-surgical weight loss treatment. The method is to use an endoscope to inject silicone water balloon with saline into the stomach for 4-6 months to reduce stomach volume and fasting feeling, thus reducing eating. After the gastric water balloon is inserted, eating low-calorie food and increasing activity can help to feel full in advance, thus achieving more significant weight loss effect.

Sponsored by the Society of Digestive Endoscopy of Chinese Medical Association and undertaken by Guangdong Medical Association and Nanfang Hospital affiliated to Southern Medical University, the First National Conference on Intestinal Diseases was held in Guangzhou from August 19 to 21, 2005. 668 participants attended the conference and 152 papers were received. The topics of the conference included diagnosis and treatment of early colorectal cancer, diagnosis and treatment of inflammatory bowel disease, diagnosis and treatment of infectious bowel disease, total enteroscopy, diagnosis of causes of small intestinal bleeding, enteral nutrition and surgical treatment of small intestinal diseases, etc.