Efficacy and safety of Elian Granules in treating chronic atrophic gastritis: study protocol for a randomized, double-blind, placebo-controlled, multicenter clinical trial.

BACKGROUND: Multifocal atrophic gastritis and intestinal metaplasia are considered to be important links in the gastric precancerous cascade. However, there are no specific drugs for these conditions. Although many studies have shown that traditional Chinese medicine is effective with no serious side effects, these studies have not been scientifically rigorous trials. Our aim is to design a high-quality trial for a Chinese patent medicine, Elian Granules, to investigate its efficacy and safety in treating patients with chronic atrophic gastritis with or without intestinal metaplasia. METHODS: This is a phase II, randomized, double-blind, placebo-controlled, multicenter clinical trial. A total of 240 participants will be assigned to a treatment or placebo control group in a 1:1 ratio. The experimental drug or placebo will be taken with boiling water, two small bags (24.2 g) each time, twice a day, half an hour after a meal, for 24 weeks. The primary outcome is the observation of histological changes in the gastric mucosa of patients with atrophic gastritis with or without intestinal metaplasia after 6 months based on the OLGA/OLGIM staging systems. The secondary outcomes include the assessment of dyspepsia and quality of life based on the dyspepsia symptom score and the quality-of-life scale. DISCUSSION: This study is designed to evaluate the efficacy and safety of Elian Granules in a randomized, double-blind, placebo-controlled, multicenter manner. This trial may not only provide evidence for a phase III clinical trial, but also an alternative option for the treatment of chronic atrophic gastritis (CAG). TRIAL REGISTRATION: Registry Platform For Evidence-Based Traditional Chinese Medicine ChiMCTR2000003929 . Registered on 13 September 2020.

Resveratrol inhibits bile acid-induced gastric intestinal metaplasia via the PI3K/AKT/p-FoxO4 signalling pathway.

Gastric intestinal metaplasia (GIM) is the essential pre-malignancy of gastric cancer. Chronic inflammation and bile acid reflux are major contributing factors. As an intestinal development transcription factor, caudal-related homeobox 2 (CDX2) is key in GIM. Resveratrol has potential chemopreventive and anti-tumour effects. The aim of the study is to probe the effect of resveratrol in bile acid-induced GIM. We demonstrated that resveratrol could reduce CDX2 expression in a time- and dose-dependent manner in gastric cell lines. A Cignal Finder 45-Pathway Reporter Array and TranSignal Protein/DNA Array Kit verified that resveratrol could increase Forkhead box O4 (FoxO4) activity and that Chenodeoxycholic acid (CDCA) could reduce FoxO4 activity. Furthermore, bioinformatics analysis showed that FoxO4 could bind to the CDX2 promoter, and these conjectures were supported by chromatin-immunoprecipitation (ChIP) assays. Resveratrol can activate FoxO4 and decrease CDX2 expression by increasing phospho-FoxO4 nucleus trans-location. Resveratrol could increase FoxO4 phosphorylation through the PI3K/AKT pathway. Ectopic FoxO4 expression can up-regulate FoxO4 phosphorylation and suppress CDCA-induced GIM marker expression. Finally, we found a reverse correlation between p-FoxO4 and CDX2 in tissue arrays. This study validates that resveratrol could reduce bile acid-induced GIM through the PI3K/AKT/p-FoxO4 signalling pathway and has a potential reversing effect on GIM, especially that caused by bile acid reflux.

[Effect of modified Zhengqi Powder in treating chronic gastritis and on patients' life quality and inflammatory factors].

Chronic gastritis is a kind of chronic gastric mucosal inflammation caused by many factors.Intestinal metaplasia refers to the transformation of gastric mucosal epithelial cells into small/large intestinal mucosal epithelium containing Panette or goblet cells.Chronic gastritis has the highest incidence among stomach diseases,while intestinal metaplasia is the serious manifestation of chronic gastritis.In this experiment,the therapeutic effect of modified Zhengqi Powder on mild intestinal metaplasia in chronic gastritis and on patients' quality of life and inflammatory reaction was investigated to analyze the efficacy and mechanism of traditional Chinese medicine prescription.From April 2016 to April 2017,120 patients of chronic gastritis with mild intestinal metaplasia were selected and divided into two groups according to the envelope method.The control group(60 cases) was treated with famoxetine.After one month of continuous treatment,the total effective rate of treatment in the observation group was 93.3%,which was much higher than 80.0% in the control group.Health questionnaire(SF-36),serum C-reactive protein(CRP),interleukin-8(IL-8) and tumor necrosis factor-α(TNF-α) levels were significantly higher than those in the control group(P<0.05).The results showed that modified Zhengqi Powder has a significant efficacy in treat chronic gastritis with mild intestinal metaplasia,and can obviously alleviate clinical symptoms and intestinal metaplasia,remove inflammatory factors and improve the quality of life of patients,and is worth promotion.

[Medicine-syndrome research and analysis of professor Li Dian-gui in treating chronic atrophic gastritis with intestinal metaplasia].

In this article, medication characteristics of professor Li Dian-gui in treating chronic atrophic gastritis with intestinal metaplasia(CAGIM) were analyzed through traditional Chinese medicine inheritance support system(version 2.5). 276 cases and 625 prescriptions were collected to analyze five types of traditional Chinese medicine(TCM) syndromes and the medicine-syndrome correlation. The results showed that medication characteristics of professor Li Dian-gui in treating CAGIM included drug combination of aromatic medicine bitter-cold herbs, preferring to activating to invigorate the spleen and good at using the qi-regulating drugs. It demonstrated that we can adopt the therapy of Huazhuo Jiedu and Xingpi Xingqi therapies in treating CAGIM in addition to the traditional approach of nourishing Yin and activating blood circulation, opening up a novel approach for TCM in healing the pathema.

[Clinical therapy of Zisheng decoction recipe for chronic atrophic gastritis with intestinal metaplasia].

To explore the therapeutic effect and security of Zisheng decoction recipein treatment of the chronic atrophic gastritis (CAG) with intestinal metaplasia(IM). A total of 147 eligible cases were randomly divided into the traditional Chinese medicine group, Western medicine group and the combined group,47 cases in each group. Zisheng decoction recipe, famotidine, as well as Zisheng decoction recipe + famotidine were respectively given in the above three groups, with a treatment course of 30 d. The symptoms of traditional Chinese medicine, pathological score of gastric mucosa and the negative rate of Helicobacter pylori before and after treatment were observed in each group.The changes in pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (GAS-17) and endothelin-1 (ET-1)were also detected to compare the efficient and safety indexes in the three groups. The combined group was better than the traditional Chinese medicine groupand the Western medicine group in total effective rate (P<0.05), pathological score of gastric mucosa and the negative rate of Helicobacter pylori, and serum indexes improvement (P<0.05). The improvement in TCM symptom score was more obvious in traditional Chinese medicine group and combined group than the Western medicine group (P<0.05). In the comparison ofincidence of complications,heart, liver and renal dysfunction, the traditional Chinese medicine group (2 case,4.8%)< the combined group (7 case,15.2%)

Effect of Saraca asoca (Asoka) on estradiol-induced keratinizing metaplasia in rat uterus.

BACKGROUND: Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta, are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. METHODS: Endometrial thickening was induced by intraperitoneal injection of estradiol (20 µg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. RESULTS: Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. CONCLUSIONS: Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.

Kalanchoe pinnata inhibits mast cell activation and prevents allergic airway disease.

Aqueous extract of Kalanchoe pinnata (Kp) have been found effective in models to reduce acute anaphylactic reactions. In the present study, we investigate the effect of Kp and the flavonoid quercetin (QE) and quercitrin (QI) on mast cell activation in vitro and in a model of allergic airway disease in vivo. Treatment with Kp and QE in vitro inhibited degranulation and cytokine production of bone marrow-derived mast cells following IgE/FcɛRI crosslinking, whereas treatment with QI had no effect. Similarly, in vivo treatment with Kp and QE decreased development of airway hyperresponsiveness, airway inflammation, goblet cell metaplasia and production of IL-5, IL-13 and TNF. In contrast, treatment with QI had no effect on these parameters. These findings demonstrate that treatment with Kp or QE is effective in treatment of allergic airway disease, providing new insights to the immunomodulatory functions of this plant.

[Effect of antioxidant use in dietary therapy in patients with chronic athrofic hastritis].

In the 1-year double-blind placebo-controlled intervention trial, it was shown that daily supplementation of patients with gastric premalignant lesions (intestinal metaplasia, IM) with a complex, containing Ester-C with antioxidantsand (2100 mg of Ca-ascorbate + 340 mg of bioflavonoids), produced a sharp decrease of abnormally high ornithine decarboxylase activity in IM gastric mucosa that was accom panied by practically total IM regression in 11 of 18 (61%) patients.

[Clinical study on modified sijunzi decoction in treating intestinal metaplasia of gastric mucosa].

OBJECTIVE: To investigate the effects of Modified Sijunzi decoction (MSJZD) in treating gastric pre-cancerous lesion. METHODS: Two hundreds and two patients with chronic gastritis and intestinal metaplasia (IM) of gastric mucosa diagnosed by gastroscopy and pathological examination of biopsy were divided into 2 groups, 117 cases of the treatment group were treated with MSJZD and 85 cases of the control group were treated with Weimeisu. For both groups, re-examination was taken after a 3-month treatment. RESULTS: The cure rate and total effective rate of IM in the treatment group were 55.6% and 87.2% respectively, while in the control group were 11.8% and 55.3% respectively (P < 0.01). CONCLUSIONS: The intestinal metaplasia process of gastric mucosa is reversible and MSJZD has good effect on it. This study provided a new way of pre-cancerous lesion treatment and gastric cancer prevention.

Inhibition of lipopolysaccharide-induced pulmonary emphysema by intratracheally instilled recombinant secretory leukocyte proteinase inhibitor.

Experiments were performed to test whether recombinant secretory leukocyte proteinase inhibitor (rSLPI) was able to prevent the development of lipopolysaccharide (LPS)-mediated pulmonary emphysema, hemorrhage, and secretory cell metaplasia (SCM) in hamsters. Several groups of eight animals were intratracheally treated for four weeks, twice a week with 0.5 mg Escherichia coli LPS or with saline. In the first experiment, an additional group of eight hamsters was treated with 0.5 mg LPS mixed with 0.5 mg rSLPI, and the animals received another instillation of 0.5 mg rSLPI 7 h later. In the second experiment, 0.5 mg LPS, mixed with 1 mg rSLPI, was given while additional instillations of 1 mg rSLPI were performed 7 h and 31 h after the first dosage. In the third experiment, 0.5 mg LPS, mixed with 0.5, 1.5, or 3.0 mg rSLPI, was given while additional instillations of 0.5, 1.5, and 3.0 mg rSLPI, respectively, were performed 24 h and 48 h after the first dosage. Hamster lungs were examined for emphysema, hemorrhage, and SCM. In all three series of experiments, we observed a significant inhibition of LPS-mediated emphysema by rSLPI. This inhibition tended to be dose related. Inconclusive results were obtained on the inhibition of LPS-mediated hemorrhage. The development of LPS-mediated SCM was not affected by rSLPI. The LPS-mediated polymorphonuclear leukocyte (PMN) influx did not change when administrations of rSLPI were given additionally. We conclude that rSLPI is able to diminish significantly the development of LPS-mediated pulmonary emphysema in hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Topical retinoic acid in dysplastic and metaplastic keratinization of corneoconjunctival epithelium.

We report four cases of corneoconjunctival keratinization that were successfully treated with topical retinoic acid ointment. In two cases keratinization was due to squamous metaplasia and in two others it was secondary to intraepithelial corneoconjunctival neoplasia. Treatment reversed severe keratinization in a case of drug-induced pseudopemphigoid and stabilized the disease in one of the two affected eyes without additional treatment. In a case of ocular cicatricial pemphigoid, retinoic acid was useful as an adjuvant therapy to immunosuppression, by reversing keratinization of the conjunctiva. In two cases of corneoconjunctival neoplasia, lesions regressed markedly. Long-term treatment was well tolerated in three patients. Our findings suggest that retinoic acid ointment is effective in treating severe squamous metaplasia in cicatrizing diseases of the conjunctiva. Our findings indicate further that retinoic acid seems to inhibit growth of corneoconjunctival neoplasias and thus might be useful complementary therapy in this situation.