1.Mechanisms of Helicobacter pylori virulence factor CagA in promoting inflammatory response by targeting SHARPIN
Nayun SU ; Tingyi WANG ; Qianfei ZUO ; Qian LU ; Zhe ZHAO ; Hao MEI ; Bin WANG ; Dongfeng CHEN ; Chunhui LAN
Immunological Journal 2023;39(12):1021-1027
Chronic inflammation induced by Helicobacter pylori is considered to be one of the main causes of gastric cancer,and CagA is a main virulence factor of H.pylori.The study aimed to investigate the role and mechanism of CagA in host inflammatory response.Mass spectrometry was used to identify the interacting proteins of CagA in AGS cells.By immunoprecipitation and immunofluorescence,the interaction was validated.Pathway expression was detected by immunoblotting after knockdown by using siRNA,and mRNA levels of inflammatory cytokines were detected by quantitative PCR.CagA-induced inflammatory responses were detected in clinical samples using hemoglobin-eosin staining(H&E).Data showed that CagA interacted with SHARPIN.And CagA activated the NF-κB signaling pathway and upregulated the mRNA and protein levels of the inflammatory cytokines IL-6,IL-8,and TNF-α,as compared with the CagA knockout strain(all P<0.05).Knockdown of SHARPIN by siRNA reduced inflammation levels and partially inhibit NF-κB signaling.In clinical samples,CagA-positive samples exhibited stronger inflammatory responses.To sum up,CagA promoted the host inflammatory response,and CagA-induced inflammatory response was reduced when SHARPIN was partially inhibited,suggesting that CagA activates the NF-κB signaling pathway through binding to SHARPIN.
2. Factors Affecting the Initial Eradication Rate of Helicobacter pylori Infection
Zhe ZHAO ; Jingtao ZHAO ; Hao MEI ; Jie HU ; Nayun SU ; Yangjie ZHU ; Yi ZHANG ; Jing YANG ; Chunhui LAN
Chinese Journal of Gastroenterology 2021;26(3):145-150
Background: Helicobacter pylori (Hp) infection is related to the occurrence of many upper digestive tract diseases, and the eradication rate has been decreasing year by year. Aims: To investigate the risk factors affecting initial eradication rate of Hp infection. Methods: Clinical data of 428 patients with Hp infection were retrospectively analyzed. Four regimens (14-day esomeprazole 20 mg + amoxicillin 750 mg, qid; 10-day esomeprazole 20 mg + amoxicillin 750 mg, qid; 14-day esomeprazole 20 mg + amoxicillin 1 000 mg, tid; 14-day esomeprazole 20 mg + bismuth 220 mg + amoxicillin 1 000 mg + clarithromycin 500 mg, bid) were given, and effect of antibiotic resistance on Hp eradication was analyzed, the relevant risk factors affecting the eradication rate of Hp were investigated. Results: The eradication rate of ITT analysis was 86.4%, PP analysis was 87.6%. The eradication rates of 4 regimens for ITT analysis were 90.8%, 79.8%, 82.7%, 91.9%, respectively, and were 90.8%, 81.2%, 85.1%, 92.7% for PP analysis, respectively. The antibiotic resistance rate was 30.3%, 97.4% and 36.8% for clarithromycin, metronidazole and levofloxacin, respectively. The recurrence rate of 116 patients was 4.3% after one year of eradication. Smoking, poor compliance, CYP2C19 gene polymorphism were risk factors for eradication rate of Hp (P<0.05). Conclusions: Smoking, poor compliance and ultra-rapid metabolizers, extensive metabolizers of CYP2C19 gene polymorphism can reduce Hp eradication rate. In clinical practice, patient education should be strengthened to urge patients to quit smoking. The quality of follow-up should be improved and proton pump inhibitor that has less impact on CYP2C19 gene polymorphism should be used, thereby increase the Hp eradication rate.
3. Efficacy and Safety of Helicobacter pylori Eradication in the Elderly: A Propensity Score Matching Analysis
Nayun SU ; Ling FAN ; Hao MEI ; Jie HU ; Yuxiang LIU ; Chunhui LAN
Chinese Journal of Gastroenterology 2022;27(4):225-231
Background: The benefits and risks of eradicating Helicobacter pylori (Hp) should be balanced in aged people. Aims: To investigate the efficacy, safety and antibiotic resistance status of Hp eradication treatment in the elderly. Methods: Four cohorts of subjects who received Hp eradication treatment in randomized controlled trials conducted in Chongqing Daping Hospital were reviewed; the demographic and clinical data were extracted and recorded. Propensity score matching was performed to select comparable elderly group (≥60 years old) and non-elderly group (<60 years old). The eradication rate, compliance, adverse events, antibiotic resistance, and the influencing factors of eradication were analyzed in these two groups. Results: A total of 994 subjects receiving Hp eradication treatment were enrolled initially, among them, 224 were categorized as elderly group and non-elderly group by propensity score matching, with 122 subjects in each group. The Hp eradication rates were higher than 90% in both elderly and non-elderly groups, and no significant differences were observed in compliance, drug-related adverse events, and antibiotic resistance rates between these two groups (all P>0.05). Furthermore, there were no significant differences in the Hp eradication rates in terms of gender, cigarette smoking, alcohol consumption, comorbidities (hypertension, diabetes, surgical history, and inflammation), compliance, etc. in the elderly group (all P> 0.05). But in retreated elderly subjects, the resistance rate of clarithromycin was higher than that in naïve elderly subjects (P<0.05). Smoking and poor compliance were identified as independent risk factors for Hp eradication by multivariate Logistic regression analysis. Conclusions: Hp eradication in the elderly demonstrates comparable efficacy and safety with non-elderly subjects. Clarithromycin-containing regimens are not recommended for empirical retreatment in aged people.
4. Analysis of Risk Factors of Drug Resistance in Patients With Helicobacter pylori Infection
Hao MEI ; Zhe ZHAO ; Jingtao ZHAO ; Nayun SU ; Qing SHI ; Jie HU ; Jing YANG ; Yangjie ZHU ; Chunhui LAN
Chinese Journal of Gastroenterology 2022;27(2):87-91
Background: The increasing in antibiotic resistance of Helicobacter pylori (Hp) has become the main cause leading to the decreasing of the eradication rate for Hp treatment. Aims: To investigate the risk factors of drug resistance of Hp. Methods: Data on 396 patients with Hp infection from Dec. 2016 to Mar. 2021 at Army Medical University were retrospectively analyzed. Drug susceptibility test was used to evaluate the resistance of 6 antibacterial drugs (metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline and furazolidone). Unconditional Logistic regression was used to investigate the risk factors affecting Hp antibiotic resistance. Results: In 396 patients with Hp infection, the resistance rates of metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline and furazolidone were 96.5%, 45.5%, 41.9%, 0.3%, 0.3% and 0, respectively. Multivariate analysis showed that previous regimen containing clarithromycin was a risk factor for clarithromycin resistance (P<0.001), and age > 40 years old was a risk factor for levofloxacin resistance (P< 0.001). Conclusions: The resistance rates of metronidazole, clarithromycin and levofloxacin are relatively high, and regimens containing these antibiotics should be avoided without the support from drug susceptibility results, especially in patients who have accepted clarithromycin‑containing regimen or more than 40 years old. Amoxicillin, tetracycline and furazolidone should be recommended preferentially for Hp treatment empirically.