Efficacy and safety of vonoprazan-based dual therapy and esomeprazole-based dual therapy in eradicating primary Helicobacter pylori infection: A propensity score matching analysis.

BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.

Eradication rates of Helicobacter pylori in treatment-naive patients following 14-day vonoprazan-amoxicillin dual therapy: A multicenter randomized controlled trial in China.

BACKGROUND: Potassium-competitive acid blockers (P-CAB) are recommended for the treatment of Helicobacter pylori infections, but dual therapy of P-CAB with amoxicillin has been poorly studied. The current study compared the efficacy, adverse reactions, compliance, and effects on gut microbiota of 14-day vonoprazan-amoxicillin (VA) dual therapy with esomeprazole, bismuth potassium citrate, amoxicillin, and metronidazole (EBAM) quadruple therapy in treatment-naive patients with H. pylori. MATERIALS AND METHODS: This was a multicenter, open-label, randomized, and controlled, non-inferiority study. Patients (n = 194) enrolled from six centers were randomly divided into either the VA or EBAM group. H. pylori eradication was determined using 13 C urea breath tests (UBT) 4-6 weeks post-treatment. Fecal samples were collected, and gut microbial populations were analyzed by 16S rDNA and metagenomic sequencing technology. RESULTS: Eradication rates of H. pylori in the VA and EBAM groups were 88.7% and 91.8%, respectively, according to intention-to-treat (ITT) analysis; 95.6% and 96.7% with per-protocol (PP) analysis; and 94.5% and 96.7% with modified ITT (mITT) analysis (all p > 0.05). The incidence of adverse reactions in the VA group was significantly lower compared to the EBAM group, and compliance within both groups was good. There was no difference in α-diversity or microbial composition in the VA and EBAM groups at one-month post-treatment compared to baseline, except for a markedly reduced abundance of Bacteroides in the EBAM group. CONCLUSION: VA therapy achieved excellent eradication rates with low adverse reactions, good compliance, and little impact on gut microbiota. VA therapy should be recommended as a first-line treatment against H. pylori.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Diagnosis and treatment of Helicobacter pylori infection by physicians in China: A nationwide cross-sectional study.

BACKGROUND: To investigate the current state of knowledge and practice of Helicobacter pylori (H. pylori) infection management in China. MATERIALS AND METHODS: This nationwide, multicenter, cross-sectional questionnaire survey was conducted between March and April 2021 with respect to the diagnosis and treatment of H. pylori infection in 31 provinces, encompassing over 1000 hospitals in mainland China. General physician information, diagnostic and detection status, eradication treatment, reexamination and follow-up after treatment, and basic knowledge of physicians were collected and compared with the Fifth Chinese National Consensus Report on Management of H. pylori infection and the 2016 Maastricht V/Florence guidelines. The subgroup analysis was also performed. RESULTS: Of the 6873 questionnaire respondents, 48.8% were males, and 51.2% were females. Approximately, 26.5% of respondents indicated that their hospitals had dedicated clinics for managing H. pylori infection. Moreover, 88.0% of respondents prescribed a bismuth-containing quadruple regimen as the initial eradication treatment, and 92.7% deemed the gastric acid suppression critical. Furthermore, 91.0% of respondents routinely recommended a reexamination 1-2 months after eradication therapy, and 95.1% advised patients to stop PPI treatment at least 2 weeks before reexamination. The detail of following (the choice of target population/methods; the choice/availability of drugs/regimens, indications for eradication, factors influencing eradication efficacy/improvement methods and factors influencing adherence, management options/factors influencing relapse; the timing and methods, awareness of reinfection rates/prevention measures, and the approach to continuing education, awareness of guidelines, and acceptance of current core concepts of management) was also described. Subgroup analysis further revealed that significant differences were existed in being gastroenterologist or not, different education level, professional title, years of working, and provincial administrative regions. CONCLUSIONS: Chinese physicians' skills and knowledge about the diagnosis and treatment of H. pylori infection could be improved. More works on education are needed in future.

10-Day and 14-day high-dose dual therapy for the treatment of Helicobacter pylori: A propensity score matching analysis.

BACKGROUND: Inconsistent eradication rates for Helicobacter pylori have been reported worldwide with dual therapy, perhaps owing to the difference in dose administration and treatment duration. This retrospective study aimed to determine whether high-dose dual therapy (HDDT) with different regimens leads to different eradication rates. The study compares the efficacy and safety of HDDT 10-day vs 14-day and investigates the factors that might affect the eradication rates. MATERIALS AND METHODS: Two comparable treatment groups were based on propensity score matching (PSM). Patients were divided into two groups based on the therapy they underwent: 10-day HDDT and 14-day HDDT (20 mg esomeprazole and 750 mg amoxicillin, administered four times daily). The eradication rates, adverse events (AEs), patient compliance, CYP2C19 gene polymorphisms, and antibiotic resistance rates of the two groups were compared. RESULTS: The intention to treat (ITT) analysis showed that the eradication rates for 10-day and 14-day groups were 78.4% (95% CI 69.6%-87.2%) and 89.7% (95% CI 83.3%-96.2%; p = .039), respectively, while the per-protocol (PP) eradication rates were 80.0% (95% CI 71.3%-88.7%) and 92.9% (95% CI 87.4%-98.5%; p = .014), respectively. The corresponding drug-related AEs were 6.8% (6/88) and 5.7% (5/88; p = .755). No significant differences were observed between the compliance rates of the two groups. The CYP2C19 gene polymorphism had no effect on the eradication rates of the two groups. CONCLUSION: The results showed that the 14-day HDDT affords a higher H. pylori eradication rate than the 10-day HDDT.

SHARPIN stabilizes ß-catenin through a linear ubiquitination-independent manner to support gastric tumorigenesis.

BACKGROUND: Aberrant activation of Wnt/ß-catenin signaling by dysregulated post-translational protein modifications, especially ubiquitination is causally linked to cancer development and progression. Although Lys48-linked ubiquitination is known to regulate Wnt/ß-catenin signaling, it remains largely obscure how other types of ubiquitination, such as linear ubiquitination governs its signaling activity. METHODS: The expression and regulatory mechanism of linear ubiquitin chain assembly complex (LUBAC) on Wnt/ß-catenin signaling was examined by immunoprecipitation, western blot and immunohistochemical staining. The ubiquitination status of ß-catenin was detected by ubiquitination assay. The impacts of SHARPIN, a core component of LUBAC on malignant behaviors of gastric cancer cells were determined by various functional assays in vitro and in vivo. RESULTS: Unlike a canonical role in promoting linear ubiquitination, SHARPIN specifically interacts with ß-catenin to maintain its protein stability. Mechanistically, SHARPIN competes with the E3 ubiquitin ligase ß-Trcp1 for ß-catenin binding, thereby decreasing ß-catenin ubiquitination levels to abolish its proteasomal degradation. Importantly, SHARPIN is required for invasiveness and malignant growth of gastric cancer cells in vitro and in vivo, a function that is largely dependent on its binding partner ß-catenin. In line with these findings, elevated expression of SHARPIN in gastric cancer tissues is associated with disease malignancy and correlates with ß-catenin expression levels. CONCLUSIONS: Our findings reveal a novel molecular link connecting linear ubiquitination machinery and Wnt/ß-catenin signaling via SHARPIN-mediated stabilization of ß-catenin. Targeting the linear ubiquitination-independent function of SHARPIN could be exploited to inhibit the hyperactive ß-catenin signaling in a subset of human gastric cancers.

Eradication Efficacy of Modified Dual Therapy Compared with Bismuth-Containing Quadruple Therapy as a First-Line Treatment of Helicobacter pylori.

OBJECTIVES: This study assessed the effectiveness, adverse events, patient adherence, and costs of modified dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori infection in Chinese patients. We also sought to determine whether modified dual therapy could be used as an alternative first-line treatment for H. pylori infection. METHODS: A total of 232 H. pylori-infected, treatment-naive patients were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day modified dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the 2 groups. RESULTS: The modified dual therapy group achieved eradication rates of 87.9%, 91.1%, and 91.1% as determined by the intention-to-treat, per-protocol, and modified intention-to-treat analyses, respectively. The eradication rates were similar compared with the bismuth-containing quadruple therapy group: 89.7%, 91.2%, and 90.4%. In addition, modified dual therapy ameliorated variations in the CYP2C19, IL-1B-511, and H. pylori VacA genotypes. There were no significant differences in the compliance rates between the 2 groups. The modified dual therapy group exhibited significantly less overall side effects compared with the bismuth-containing quadruple therapy group (P < 0.001). Furthermore, the cost of medications in the modified dual therapy was lower compared with that in the bismuth-containing quadruple therapy. CONCLUSIONS: Modified dual therapy at high dose and administration frequency is equally effective and safer and less costly compared with bismuth-containing quadruple therapy.

Mutant selection window of clarithromycin for clinical isolates of Helicobacter pylori.

BACKGROUND: Clarithromycin-resistance is becoming a global health concern in the treatment of Helicobacter pylori (H. pylori). The mutant prevention concentration (MPC) represent the propensities of antimicrobial agents to select resistant mutants. The concentration range between the minimum inhibitory concentration (MIC) and the MPC is defined as mutant selection window (MSW). In this study, we aimed to determine the cause of increasing clarithromycin resistance by investigating the MSW for clinical isolates of H. pylori. RESULTS: A retrospective subgroup, which included 68 clarithromycin-sensitive H. pylori strains, was selected from a double-blind trial. The MICs and MPCs were determined using agar plate assays. Genotypic tests were performed using Sanger sequencing. All isolates were wild-type, and 33.82% (23/68) had a 0.016 mg/L MIC, 45.59% (31/68) had a 0.031 mg/L MIC, 16.18% (11/68) had a 0.062 ≤ MIC ≤ 0.125 mg/L, and 4.41% (3/68) had a 0.25 mg/L MIC. The MPC50/90 (mg/L) of the isolates were: 0.062/0.125, 0.125/0.5, 0.25/0.25 and 1/2, respectively. The MPCs showed a moderate correlation with the MICs (rs = 0.65, P < 0.0001). Using published data and MPC90, we calculated the time inside the MSW (TMSW) for low- and high-dose (200 or 500 mg bid) clarithromycin that were 6 and 0 h, 24 and 4 h, 15 and 2 h, 5 and 17 h for the strains with MICs (mg/L) of 0.016, 0.031, 0.062-0.125, and 0.25, respectively. CONCLUSIONS: This study showed that in the clarithromycin-sensitive clinical isolates of H. pylori, low-dose clarithromycin may lead to decreased drug sensitivity or even clarithromycin resistance; strains with a 0.25 mg/L MIC display a high risk of treatment failure.

Management of Helicobacter pylori infection by clinicians: A nationwide survey in a developing country.

BACKGROUND & AIMS: Developing countries are making efforts to improve health management. Practice deviating from the guideline means inefficient control. The study aims to investigate the management of Helicobacter pylori (H pylori) infection from a developing country perspective. METHODS: An authoritative survey was conducted in 14th (2014) and 17th (2017) Congress of Gastroenterology China, respectively. The Maastricht V/Florence consensus report was invoked as the evaluation criterion. RESULTS: A total of 4182 valid samples were included in this study. Most of the respondents (94%) updated knowledge by lectures. Respondents had a different awareness rate of H pylori-related diseases, ranging from 45% to 95%. Up to 40% of the respondents did not follow the recommendations for the diagnosis. Choice accuracy of eradication regimens and antibiotic combinations was <70%. About 20% of the respondents did not pay attention to the confirmation after the eradication. The situation had been improved in 2017 when compared with that in 2014 (all P < .05). Multivariate logistic regression analysis revealed that influencing factors including nongastroenterologists, bachelor degree and below, the primary professional title, hospital location, and a small proportion of H pylori infection in daily practice related to the deviation of consensus (all P < .05). CONCLUSIONS: Although the management of H pylori infection has been improved in a developing country, there is still a gap between the real-world practices and the consensus. Influencing factors should be taken into account in decision-making, and the corresponding population should be strengthened with precision training during the promotion of the guideline.

Furazolidone-containing triple and quadruple eradication therapy for initial treatment for Helicobacter pylori infection: A multicenter randomized controlled trial in China.

BACKGROUND: The efficacy of Helicobacter pylori (H. pylori) eradication has steadily declined, primarily because of antibiotic resistance. This study aimed to evaluate the efficacy and safety of furazolidone eradication therapies as initial treatments for H. pylori infection. METHODS: A national, multicenter, open-label, randomized controlled trial was performed at 16 sites across 13 provinces in China to evaluate the efficacy and safety of furazolidone-containing therapies for H. pylori infection. Treatment naïve patients were randomly assigned to: esomeprazole 20 mg, bismuth 220 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily for 10 and 7 days (FAB 10 and FAB 7; the same therapy without bismuth (FA 10 and FA 7). The primary and secondary outcomes were the eradication rate and regimen safety, respectively. Treatment success was assessed by the 13 C urea breath test at least 4 weeks after treatment completion. RESULTS: Overall, according to intention-to-treat (ITT) analysis, the eradication rates for FAB 10 and FAB 7 were 86.6% (95% confidence interval [CI], 79.9%-93.2%) and 83.6% (95% CI, 76.3%-90.9%) and for FA 10 and FA 7 were 82.4% (95% CI, 74.9%-89.8%) and 77.6% (95% CI, 69.4%-85.8%), respectively. According to per-protocol analysis, the overall eradication rates for FAB 10 and FAB 7 were 94.7% (95% CI, 90.3%-99.1%) and 90.8% (95% CI, 85.1%-96.5%) and for FA 10 and FA 7 were 90.6% (95% CI, 84.9%-96.3%) and 85.1% (95% CI, 78.2%-92.1%), respectively. The overall prevalence of side effects was 8.1%. CONCLUSIONS: Furazolidone-containing therapies, particularly the tested 10-day quadruple therapy, exhibited satisfactory efficacy and safety. This 10-day quadruple therapy represents a promising initial treatment strategy for Chinese patients.

Comparison of procedural sequences in same-day painless bidirectional endoscopy: Single-center, prospective, randomized study.

BACKGROUND AND AIM: To compare the efficacy and safety of esophagogastroduodenoscopy (EGD)-colonoscopy and colonoscopy-EGD sequences for patients subjected to same-day bidirectional endoscopy under remifentanil and propofol sedation. METHODS: A total of 209 eligible outpatients scheduled for diagnostic same-day bidirectional endoscopy between 16 February 2016 and 30 April 2016 were randomly assigned to the EGD-colonoscopy (n = 106) and colonoscopy-EGD (n = 103) sequence groups. Primary endpoint was total dose of propofol required for the procedure. Secondary endpoints included duration of endoscopy, patient satisfaction, adverse effects, endoscopy findings, and cardiopulmonary responses of the patients. RESULTS: Patients in the two groups were similar in terms of demographic and clinical data (P > 0.05). EGD-colonoscopy sequence group had lesser requirement of propofol for sedation (P < 0.05), faster recovery (P < 0.001), and lesser influence on mean arterial pressure (MAP) during the endoscopy (P < 0.05). Duration of EGD and colonoscopy, patient satisfaction, adverse effects, and pathological findings did not differ between the two groups. CONCLUSIONS: The EGD-colonoscopy sequence may be considered the preferred sequence for same-day bidirectional endoscopy as a result of less cardiovascular stress, lessened need for sedation with propofol, and faster recovery.

A 21-35 kDa Mixed Protein Component from Helicobacter pylori Activates Mast Cells Effectively in Chronic Spontaneous Urticaria.

BACKGROUND: Helicobacter pylori (H. pylori) seem to involve in the etiology of chronic spontaneous urticaria (CSU). But studies of the pathogenic mechanism are very little. METHODS: In this study, we detected the serum-specific anti-H. pylori IgG and IgE antibodies in 211 CSU and 137 normal subjects by enzyme-linked immunosorbent assay (ELISA), evaluated the direct activation effects of H. pylori preparations and its protein components on human LAD2 mast cell line in vitro, and analyzed the specific protein ingredients and functions of the most effective H. pylori mixed protein component using liquid chromatography-mass spectrometry and ELISA assay. RESULTS: In CSU patients, the positive rate of anti-H. pylori IgG positive rate was significantly higher than that in normal controls, and the anti-H. pylori IgE levels had no statistical difference between H. pylori-infected patients with and without CSU. Further studies suggested that H. pylori preparations can directly activate human LAD2 mast cell line in a dose-dependent manner and its most powerful protein component was a mixture of 21-35 kDa proteins. Moreover, the 21-35 kDa mixed protein component mainly contained 23 kinds of proteins, which can stimulate the release of histamine, TNF-a, IL-3, IFN-γ, and LTB4 by LAD2 cells in a dose-dependent or time-dependent manner. CONCLUSIONS: A 21-35 kDa mixed protein component should be regarded as the most promising pathogenic factor contributing to the CSU associated with H. pylori infection.

Cortactin Mediates Apoptosis of Gastric Epithelial Cells Induced by VacA Protein of Helicobacter pylori.

BACKGROUND: Vacuolating cytotoxin antigen (VacA) is one of the major virulence factors in Helicobacter pylori (H. pylori), which is responsible for cell vacuolar degeneration and apoptotic cell death. A candidate host factor which mediates this process is cortactin, a protein associated with the processes of colonization and adhesion of H. pylori in gastric epithelium. AIM: To investigate the role of cortactin in VacA-induced apoptosis of gastric epithelial cells. METHODS: Cortactin expression and shRNA lentiviral constructs were developed and transduced into the human gastric cancer cell line, AGS. VacA protein was purified from H. pylori cultures, acid-activated, and co-incubated with the transduced cell populations. Apoptosis was detected by flow cytometry, and the levels of the pro- and anti-apoptotic proteins Bax and Bcl-2 were determined by Western blot. RESULTS: Acid-activated purified VacA induced apoptosis in the parental AGS cells. Increased expression of cortactin (AGS/cortactin) led to a greater percentage of cells undergoing apoptosis. In contrast, knockdown of cortactin with shRNA (AGS/cortactin-shRNA) decreased the percentage of apoptotic cells. The protein levels of pro- and anti-apoptotic proteins Bax and Bcl-2 were increased and decreased in AGS/cortactin cells relative to the parental AGS cells. In the AGS/cortactin-shRNA cells, Bax protein levels were decreased, while Bcl-2 protein was increased. CONCLUSIONS: The results indicate that cortactin is involved in the regulation of apoptosis induced by VacA in gastric cells.

Etomidate-remifentanil is more suitable for monitored anesthesia care during gastroscopy in older patients than propofol-remifentanil.

BACKGROUND: This prospective and randomized study was designed to compare safety, potential complications, and patient and examiner satisfaction of 2 anesthetic combinations - etomidate-remifentanil and propofol-remifentanil - in elderly patients undergoing diagnostic gastroscopy. MATERIAL AND METHODS: A group of 720 patients, aged 60-80 years, scheduled for diagnostic gastroscopy under sedation were prospectively randomized. After 0.4-0.6 µg kg⁻¹ of remifentanil was infused, etomidate or propofol was administered. Patients in the etomidate group received doses of etomidate at 0.1-0.15 mg kg⁻¹ followed by 4-6 mg. Patients in the propofol group received doses of propofol at 1-2 mg kg⁻¹ followed by 20-40 mg. Physiological indexes were evaluated for the 715 of 720 patients that completed the treatment. The onset time, duration time, and discharge time were recorded. Physicians, anesthetists, and patients were surveyed to assess their satisfaction. RESULTS: Systolic pressure and diastolic pressure decreased significantly after the procedure in the propofol group (P<0.001). The average heart rate was significantly lower in the propofol group (P<0.05). No periods of desaturation (SpO2 <95%) were observed in either group. The onset time was earlier in the etomidate group (P=0.00). All adverse events, with the exception of myoclonus, were greater in the propofol group, and physician and patient satisfaction in both groups was similar. CONCLUSIONS: Etomidate-remifentanil administration for sedation and analgesia during gastroscopy resulted in more stable hemodynamic responses and less adverse events in older patients.

Efficacy and safety of esomeprazole with flupentixol/melitracen in treating gastroesophageal reflux disease patients with emotional disorders.

BACKGROUND AND AIM: This study was designed to demonstrate the safety and efficacy of esomeprazole combined with flupentixol/melitracen for the treatment of gastroesophageal reflux disease (GERD) patients with emotional disorders. METHODS Two hundred eighty-nine GERD patients with emotional disorders were divided randomly into two groups: group 1 received esomeprazole only (monotherapy) and group 2 received esomeprazole and flupentixol/melitracen (combination therapy). The patients' GERD questionnaire (GerdQ) and hospital anxiety and depression (HAD) scores were obtained before and after treatment. Changes in the scores, rates of symptom remission, and adverse effects were compared between the two groups. RESULTS: After 2 weeks of treatment, the average decrease in GerdQ score in the combination group (4.04 ± 2.34) was significantly greater than that in the monotherapy group (3.34 ± 2.74; P < 0.05). Significant differences between the two groups were also found for changes in HAD anxiety scores (5.45 ± 2.41 vs 3.34 ± 2.43, P < 0.05), depression scores (5.47 ± 2.47 vs 3.00 ± 3.28, P < 0.05), and anxiety-depression scores (5.20 ± 2.71 vs 3.60 ± 2.56, P < 0.05). The remission of symptoms (eructation, abdominal pain, anorexia, and other accompanying symptoms) in the combination group was significantly better than that in the monotherapy group, and no significant difference in the incidence of adverse events was observed between the two groups. CONCLUSIONS: The combination therapy has better efficacy than the monotherapy in improving the symptoms of gastroesophageal reflux in patients with emotional disorders. In addition, this combination treatment is safe, with a low incidence of adverse events.

Knockdown of nucleostemin can inhibit the proliferation of esophageal carcinoma cells in vitro through upregulating p21.

BACKGROUND/AIMS: Esophageal squamous cell carcinoma is a common digestive tract cancer with poor prognosis. Nucleostemin is a nucleolar protein expressed in stem and cancer cells, involved in the regulation of cell proliferation. p21 plays an important role in negative regulation of the cell-cycle. We investigated the role of nucleostemin through regulating p21 expression in the occurrence and progression of human esophageal carcinoma. METHODOLOGY: The expression of nucleostemin and p21 protein and of nucleostemin was knocked-down by means of RNA interference (RNAi) in Eca109 cells. Then, mRNA and protein expressions of nucleostemin and p21 were determined by reverse transcriptase polymerase chain reaction and Western blotting, respectively. In addition, the effect of nucleostemin RNAi on cell proliferation and cell cycle distribution of Eca109 cells were observed. RESULTS: Nucleostemin was high expressed, but p21 was low expressed in esophageal carcinoma tissues while increased level of nucleostemin protein was associated with reduced p21. inhibition of nucleostemin resulted in an increased expression of p21 and inhibition of cell proliferation, cause G1/G0 phase cells increased and S-phase cells reduced greatly in Eca109 cells. CONCLUSION: Silence of nucleostemin inhibit cell proliferation through up-regulating p21 expression and nucleostemin may be involved in the pathogenesis of esophageal squamous cell carcinoma.

Comparison of the efficacy between the dual therapy of tegoprazan and the quadruple therapy of tegoprazan: A randomized, controlled, multicenter study.

INTRODUCTION: Tegoprazan (TPZ), a potassium-competitive acid blocker, exerts a strong acid-suppression effect and a rapid onset of action. However, research on TPZ-amoxicillin (TA) dual treatment is limited. Here, we compared the safety and efficacy of TPZ-amoxicillin dual treatment and TPZ, bismuth potassium citrate, amoxicillin, and clarithromycin (TBAC) quadruple therapy in patients newly diagnosed with H. pylori infection over a 14-day treatment period. METHODS: A total of 236 patients newly diagnosed with H. pylori were enrolled in this multi-center, prospective, open-label, and randomized controlled study. Patients randomly received either TA dual or TBAC quadruple therapy. The incidence of adverse reactions and treatment compliance were recorded and then analyzed. RESULTS: The intention-to-treat analysis revealed that H. pylori-eradication rates were 83.9% (95% confidence interval [CI] 78.2%-91.3%) and 81.4% (95% CI 74.2%-88.5%) for the TA and TBAC groups, respectively, with no statistically significant difference between them (P = 0.606). The per-protocol analysis revealed that the H. pylori-eradication rates were 88.3% and 84.8% for the TA and TBAC groups, respectively (P = 0.447). The incidence of adverse reactions was significantly lower in the TA group than in the TBAC group (4.2% vs. 15.3%, P = 0.004). Moreover, the TA group demonstrated substantially higher treatment compliance than the TBAC group (94.1% vs. 89.0%, P = 0.020). CONCLUSION: The TA dual therapy successfully eradicated H. pylori with a high eradication rate and a low incidence of adverse reactions. Therefore, this treatment is recommended as an alternative course for patients newly diagnosed with H. pylori infection.

High expression of lysine-specific demethylase 1 correlates with poor prognosis of patients with esophageal squamous cell carcinoma.

Recent studies have elucidated the role of lysine-specific demethylase 1 (LSD1), a member of the histone demethylases, in epigenetic regulation of tumor suppressing/promoting genes and neoplastic growth. However, the expression of LSD1 in patients with esophageal squamous cell carcinoma (ESCC) is still unknown. Here, we reported that LSD1 expression was elevated in cancerous tissue and correlated with lymph node metastasis and poorer overall survival in patients with ESCC. Compared to EC109 cells, LSD1 expression was unregulated in aggressive cancer cell lines KYSE450 and KYSE150. Knockdown of LSD1 using lentivirus delivery of LSD1-specific shRNA abrogated the migration and invasion of ESCC cells in vitro. Further, a LSD1 inhibitor, tranylcypromine, suppressed H3K4me2 demethylation and attenuated cellular motility and invasiveness in a dose-dependent manner. Taken together, these data suggested that LSD1 was a potential prognostic maker and may be a molecular target for inhibiting invasion and metastasis in ESCC.