INDUCTION OF GASTRIC INTRAEPITHELIAL NEOPLASIA OF GLANDULAR STOMACH OF MONGOLIAN GERBILS BY ELICOBACTER PYLORI

Objective： To setup an animal model of gastric carcinogenesis by Helicobacter pylori （Hp） for basic, prevention and therapeutic research of Hp-related diseases. Methods： 22 young male Mongolian gerbils were administrated with suspension of Hp strain TN2 by intragastric garage for 5 consecutive times （4×10^8 CFU/time, 1 time/4 days）. 10 male gerbils were used as negative control. Two infected gerbils were killed at 10, 20, and 30 weeks, respectively, after inoculation to monitor the development of gastric lesions. Other animals were killed at 40 experimental weeks. Pathological changes of glandular stomach were examined histologically. Results： Gastric intraepithelial neoplasias （GIN） and low-grade dysplasias were observed only in the pyloric antrum of Hp-treated gerbils （3 and 2 ones, respectively）, but not in control group （5/13 vs. 0/10, P〈0.04）. High incidence of chronic active gastritis and chronic atrophic gastritis were observed in Hp-treated animals （10/13, 76.9%）. Low incidence of chronic atrophic gastritis was also detected in negative control gerbils （3/10, 30%; P〈0.04）. Conclusion： Hp inoculation could induce chronic inflammation and malignant lesions of the glandular stomach of Mongolian gerbils conveniently.

Suppressing FXR promotes antiviral effects of bile acids via enhancing the interferon transcription

Bile acids(BAs)are natural metabolites in mammals and have the potential to function as drugs against viral infection.However,the limited understanding of chenodeoxycholic acid(CDCA)receptors and downstream signaling,along with its lower suppression efficiency in inhibiting virus infection limits its clinical application.In this study,we demonstrate that farnesoid X receptor(FXR),the receptor of CDCA,negatively regulates interferon signaling,thereby contributing to the reduced effectiveness of CDCA against virus replication.FXR deficiency or pharmacological inhibition enhances interferon signaling activation to suppress virus infection.Mechanistically,FXR impairs the DNA binding and transcriptional abilities of activated interferon regulatory factor 3(IRF3)through interaction.Reduced IRF3 transcriptional activity by FXReIRF3 interaction significantly undermines the expression of Interferon Beta 1(IFNB1)and the antiviral response of cells,especially upon the CDCA treatment.In FXR-deficient cells,or when combined with Z-guggulsterone(GUGG)treatment,CDCA exhibits a more potent ability to restrict virus infection.Thus,these findings suggest that FXR serves as a limiting factor for CDCA in inhibiting virus replication,which can be attributed to the“signaling-brake”roles of FXR in interferon signaling.Targeting FXR inhibition represents a promising pharmaceutical strategy for the clinical application of BAs metabolites as antiviral drugs.

Dahuang Fuzi decoction reduces inflammation levels and alleviates intestinal mucosal barrier damage in septic rats

Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.

Rheumatoid arthritis treated with the triple strong-stimulation technique of acupuncture and moxibustion at specific acupoints:A randomized controlled trial

Objective: To explore the clinical therapeutic effects and the mechanism on rheumatic arthritis(RA)treated with the combination of the instruments and techniques of acupuncture and moxibusiton.Methods: A total of 60 RA patients were randomized into an observation group and a control group,30 cases in each one. In the control group, diclofenac sodium sustained release tablets were prescribed for oral administration, 0.3 g each time, twice a day, methotrexate tablets(MTX) for oral administration,10 mg each time, once a week and folic acid tablets for oral administration, 5 mg each time, once a week. In the observation group, besides the treatment with western medicines, simultaneously, the specific acupoints were selected and stimulated with the triple strong-stimulation therapy, in which, the strong bloodletting technique, the strong cupping technique and the strong moxibustion technique were combined together, with different instruments of acupuncture and moxibustion adopted. The treatment was given once every 3 days, consecutively for 10 times. In 30 days of treatment, the therapeutic effects were observed in the two groups. Separately, before and after treatment, the rheumatoid factors(RF),hypersensitive-C reactive protein(hs-CRP) and erythrocyte sedimentation rate(ESR), the scores of joint symptoms and physical signs as well as the disease activity score(DAS-28) were observed in the two groups.Results: Regarding RF, there were statistical significant differences before and after treatment in the observation group and the control group(the observation group 248.01 ± 79.81 vs 31.17 ± 29.01,the control group 254.11 ± 72.16 vs 66.42 ± 37.07, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment(P < 0.05). Regarding hs-CRP, there were statistical significant differences before and after treatment in the observation group and the control group(the observation group 26.12 ± 9.22 vs 8.98 ± 7.66, the control group 23.18 ± 7.18 vs 16.01 ± 5.02, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment(P < 0.05). Regarding ESR, there were statistical significant differences before and after treatment in the observation group and the control group(the observation group 30.56 ± 11.38 vs 12.58 ± 5.91,the control group 35.52 ± 9.67 vs 21.47 ± 6.91, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment(P < 0.05). Regarding DAS-28, there were statistical significant differences before and after treatment in the observation group and the control group(the observation group 8.89 ± 2.01 vs 3.01 ± 0.74, the control group 8.14 ± 1.38 vs 4.12 ± 0.96, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment(P < 0.05). Regarding the quantitative grading score of symptom, there were statistical significant differences before and after treatment in the observation group and the control group(the observation group 7.87 士 1.69 vs 3.82 ±1.96, the control group 7.77 ± 1.68 vs 5.01 ± 11.23, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment(P < 0.05).The total effective rate was 96.67%(29/30) in the observation group and was 80.0%(24/30) in the control group, indicating the statistical significant difference between the two groups(P < 0.01).Conclusion: Based on western medications, the triple strong-stimulation therapy of acupuncture and moxibustion at specific acupoints significantly relieves the joint symptoms, reduces the inflammatory reaction indicators and improves the clinical therapeutic effects on RA in the patients.