A Photoisomerizable Zinc (II) Complex Inhibits Microtubule Polymerization for Photoactive Therapy.

The photoisomerization-induced cytotoxicity in photopharmacology provides a unique pathway for phototherapy because it is independent of endogenous oxygen. In this study, we developed a biosafe photoisomerizable zinc(II) complex (Zn1), which releases its trans ligand (trans-L1) after being irradiated with blue light. This causes the complex to undergo photoisomerization and produce the toxic cis product (cis-L1) and generate singlet oxygen (1 O2 ). The resulting series of events caused impressive phototoxicity in hypoxic A431 skin cancer cells, as well as in a tumor model in vivo. Interestingly, Zn1 was able to inhibit tumor microtubule polymerization, while still showing good biocompatibility and biosafety in vivo. This photoisomerizable zinc(II) complex provides a novel strategy for addressing the oxygen-dependent limitation of traditional photodynamic therapy.

The management of Helicobacter pylori infection and prevention and control of gastric cancer in China.

Helicobacter pylori (H. pylori) infection, a type-1 carcinogen, was closely associated with gastric cancer (GC). Successfully eradicating H. pylori infection could reduce the incidence of GC. China was a country with high incidence of GC and high prevalence of H. pylori infection. Nearly half of worldwide GC new cases and deaths attributed to H. pylori infection occurred in China. H. pylori prevalence varied over time with the improvement of socioeconomic status and sanitary conditions. The knowledge of antibiotic resistance rate in time was important to guide the clinical choice of antibiotics use in the regimens. With the publication of five Chinese consensus reports on the management of H. pylori infection and the effort of public preach of H. pylori-related knowledge, the standardization of H. pylori diagnosis and treatment by clinicians was improved. Bismuth-containing quadruple therapy was widely applied in clinical practice of H. pylori eradication because of high efficacy and safety. High-dose Proton Pump Inhibitor-amoxicillin dual therapy or vonoprazan-amoxicillin dual therapy showed comparable efficacy and lower side effects than bismuth-containing quadruple therapy, which were the alternative choice. The diagnosis rate of early GC was low and distinguishing Chinese GC risk population for the further endoscopy screening was important. Efforts have been done to establish prediction models to stratify GC risk in the Chinese GC risk population. We reviewed the current situation of the management of H. pylori infection and prevention and control of GC in China here.

A Photoactivated Sorafenib-Ruthenium(II) Prodrug for Resistant Hepatocellular Carcinoma Therapy through Ferroptosis and Purine Metabolism Disruption.

The curative effect of sorafenib in hepatocellular carcinoma (HCC) is limited and sorafenib resistance remains a major obstacle for HCC. To overcome this obstacle, a new photoactive sorafenib-Ru(II) complex Ru-Sora has been designed. Upon irradiation (λ = 465 nm), Ru-Sora rapidly releases sorafenib and generates reactive oxygen species, which can oxidize intracellular substances such as GSH. Cellular experiments show that irradiated Ru-Sora is highly cytotoxic toward Hep-G2 cells, including sorafenib-resistant Hep-G2-SR cells. Compared to sorafenib, Ru-Sora has a significant photoactivated chemotherapeutic effect against Hep-G2-SR cancer cells and 3D Hep-G2 multicellular tumor spheroids. Furthermore, Ru-Sora inducing apoptosis and ferroptosis is proved by GSH depletion, GPX4 downregulation, and lipid peroxide accumulation. Metabolomics results suggest that Ru-Sora exerts photocytotoxicity by disrupting the purine metabolism, which is expected to inhibit tumor development. This study provides a promising strategy for enhancing chemotherapy and combating drug-resistant HCC disease.

Ferroptosis promotes sonodynamic therapy: a platinum(ii)-indocyanine sonosensitizer.

Sonodynamic therapy (SDT) has unique advantages in deep tumour ablation due to its deep penetration depth, showing great preclinical and clinical potential. Herein, a platinum(ii)-cyanine complex has been designed to investigate its potential as a SDT anticancer agent. It generates singlet oxygen (1O2) under ultrasound (US) irradiation or light irradiation, and exhibits US-cytotoxicity in breast cancer 4T1 cells but with negligible dark-cytotoxicity. Mechanistic investigations reveal that Pt-Cy reduces the cellular GSH and GPX4, and triggers cancer cell ferroptosis under US irradiation. The metabolomics analysis illustrates that Pt-Cy upon US treatment significantly dysregulates glutathione metabolism, and finally induces ferroptosis. In vivo studies further demonstrate that Pt-Cy inhibits tumor growth under US irradiation and its efficiency for SDT is better than that for PDT in vivo. This is the first example of platinum(ii) complexes for sonodynamic therapy. This work extends the biological applications of metal complexes from PDT to SDT.

An osmium-peroxo complex for photoactive therapy of hypoxic tumors.

The limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy. Herein, we report our investigation of an osmium-peroxo complex (Os2), which is inactive in the dark, but can release a peroxo ligand O2•- upon light irradiation even in the absence of oxygen, and is transformed into a cytotoxic osmium complex (Os1). Os1 is cytotoxic in the presence or absence of irradiation in hypoxic tumors, behaving as a chemotherapeutic drug. At the same time, the light-activated Os2 induces photocatalytic oxidation of endogenous 1,4-dihydronicotinamide adenine dinucleotide in living cancer cells, leading to ferroptosis, which is mediated by glutathione degradation, lipid peroxide accumulation and down-regulation of glutathione peroxidase 4. In vivo studies have confirmed that the Os2 can effectively inhibit the growth of solid hypoxic tumors in mice. A promising strategy is proposed for the treatment of hypoxic tumors with metal-based drugs.

Discovery and Validation of Novel Methylation Markers in Helicobacter pylori-Associated Gastric Cancer.

Previous studies have shown that abnormal methylation is an early key event in the pathogenesis of most human cancers, contributing to the development of tumors. However, little attention has been given to the potential of DNA methylation patterns as markers for Helicobacter pylori- (H. pylori-) associated gastric cancer (GC). In this study, an integrated analysis of DNA methylation and gene expression was conducted to identify some potential key epigenetic markers in H. pylori-associated GC. DNA methylation data of 28 H. pylori-positive and 168 H. pylori-negative GC samples were compared and analyzed. We also analyzed the gene expression data of 18 H. pylori-positive and 145 H. pylori-negative GC cases. Finally, the results were verified by in vitro and in vivo experiments. A total of 5609 differentially methylated regions associated with 2454 differentially methylated genes were identified. A total of 228 differentially expressed genes were identified from the gene expression data of H. pylori-positive and H. pylori-negative GC cases. The screened genes were analyzed for functional enrichment. Subsequently, we obtained 28 genes regulated by methylation through a Venn diagram, and we identified five genes (GSTO2, HUS1, INTS1, TMEM184A, and TMEM190) downregulated by hypermethylation. HUS1, GSTO2, and TMEM190 were expressed at lower levels in GC than in adjacent samples (P < 0.05). Moreover, H. pylori infection decreased HUS1, GSTO2, and TMEM190 expression in vitro and in vivo. Our study identified HUS1, GSTO2, and TMEM190 as novel methylation markers for H. pylori-associated GC.

Expression and prognostic significance of the DNA damage response pathway and autophagy markers in gastric cancer.

Gastric cancer (GC) is a leading cause of mortality and morbidity worldwide. We assessed the expression patterns of DNA damage response (DDR)-related markers, including ATM, CHK2, p-p53 (S15), Rad51, and BRCA2 and autophagy-related proteins including p62 and Beclin-1 in 153 GC specimens using immunohistochemistry staining. GC tissues showed lower levels of ATM, CHK2, p-p53, BRCA2, and higher levels of Rad51 compared to adjacent normal tissues. The autophagy-related protein p62 was upregulated, whereas Beclin-1 was downregulated in human GC groups. Additionally, different statuses of DDR pathways and autophagy characterized by protein expression were associated with overall survival. Our results indicated that the impairment of DNA damage and autophagy may be implicated in gastric cancer progression and its clinical prognosis.

Upregulation of oncogene Activin A receptor type I by Helicobacter pylori infection promotes gastric intestinal metaplasia via regulating CDX2.

BACKGROUND: Activin A receptor type I (ACVR1) is involved in tumorigenesis. However, the underlying molecular mechanisms of ACVR1 in gastric cancer (GC) and its association with Helicobacter pylori remained unclear. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database were utilized to explore the ACVR1 expression in GC and normal control and its association with survival. The ACVR1 was knocked out using CRISPR/Cas-9; RNA sequencing analysis was performed in AGS cells with ACVR1 knockout and normal control. Functional experiments (CCK-8, colony-forming, and transwell assays) were conducted to demonstrate the role of ACVR1 in cell proliferation, invasion, and metastasis. H. pylori-infected C57/BL6 models were established. ACVR1, p-Smad1/5, and CDX2 were detected in AGS cells cocultured with H. pylori strains. The CDX2 and key elements of BMP signaling pathway were detected in AGS cells with ACVR1 knockout and normal control. In addition, Immunohistochemistry was performed to detect the ACVR1 and CDX2 expression in gastric samples. RESULTS: ACVR1 expression was higher in GC than normal control from TCGA, GEPIA, and samples collected from our hospital (p < 0.05). ACVR1 promoted cell proliferation, migration, and invasion in vitro. Both cagA+ and cagA- H. pylori could upregulate the expression ACVR1 (p < 0.05). Downregulation of ACVR1 inhibited the H. pylori-induced cell proliferation, migration, and invasion (p < 0.05). H. pylori increased the expression of p-Smad 1/5 and CDX2. The CDX2 and key elements of BMP signaling pathway were downregulated in AGS cells with ACVR1 knockout. ACVR1 and CDX2 were upregulated in the stage of intestinal metaplasia (IM). Moreover, ACVR1 and CDX2 expressions were higher in H. pylori-positive group than H. pylori-negative group (p < 0.05). CONCLUSION: Our data indicate that H. pylori infection increases ACVR1 expression, promoting gastric IM via regulating CDX2, which is an essential step in H. pylori carcinogenesis.

Caudal type homeoboxes as a driving force in Helicobacter pylori infection-induced gastric intestinal metaplasia.

HELICOBACTER PYLORI: (H. pylori), a common pathogenic bacterium in the stomach, has been demonstrated to be a major cause of gastric cancer (GC). The typical pathological evolution of H. pylori infection-induced GC involves development from gastric atrophy, via intestinal metaplasia (IM) and dysplasia, to intestinal-type GC. During this process, IM is considered to be an "irreversible point" that significantly increases the risk for GC. Therefore, the elucidation of the mechanism underlying IM is of great significance for the prevention and treatment of gastric mucosal carcinogenesis associated with H. pylori infection. Caudal type homeoboxes (CDXs) are transcription factors involved in intestinal differentiation establishment and the maintenance of normal intestinal mucosa and IM. H. pylori infection increases the expression of CDXs through epigenetic regulation, the nuclear factor-kappaB signaling pathway and its downstream proinflammatory factors, and the transforming growth factor-beta signaling pathway, leading to the progression from normal gastric mucosa to IM. However, the precise mechanisms of gastric intestinal metaplasia have not yet been fully elucidated. In this review, we focus on research progress revealing the functions of CDXs in H. pylori infection-induced IM, as well as the regulators modulating this process.

Pancreatic necrosis and severity are independent risk factors for pancreatic endocrine insufficiency after acute pancreatitis: A long-term follow-up study.

BACKGROUND: Pancreatic endocrine insufficiency after acute pancreatitis (AP) has drawn increasing attention in recent years. AIM: To assess the impact of risk factors on the development of pancreatic endocrine insufficiency after AP. METHODS: This retrospective observational long-term follow-up study was conducted in a tertiary hospital. Endocrine function was evaluated by the oral glucose tolerance test. The data, including age, sex, body mass index, APACHE II score, history of smoking and drinking, organ failure, pancreatic necrosis, debridement of necrosis (minimally invasive and/or open surgery), and time interval, were collected from the record database. RESULTS: A total of 361 patients were included in the study from January 1, 2012 to December 30, 2018. A total of 150 (41.6%) patients were diagnosed with dysglycemia (including diabetes mellitus and impaired glucose tolerance), while 211 (58.4%) patients had normal endocrine function. The time intervals (mo) of the above two groups were 18.73 ± 19.10 mo and 31.53 ± 27.27 mo, respectively (P = 0.001). The morbidity rates of pancreatic endocrine insufficiency were 46.7%, 28.0%, and 25.3%, respectively, in the groups with different follow-up times. The risk factors for pancreatic endocrine insufficiency after AP were severity (odds ratio [OR] = 3.489; 95% confidence interval [CI]: 1.501-8.111; P = 0.004) and pancreatic necrosis (OR = 4.152; 95%CI: 2.580-6.684; P = 0.001). CONCLUSION: Pancreatic necrosis and severity are independent risk factors for pancreatic endocrine insufficiency after AP. The area of pancreatic necrosis can affect pancreatic endocrine function.

Elevated CA125 levels are associated with adverse clinical outcomes in acute pancreatitis: A propensity score-matched study.

OBJECTIVES: Glycosylation alterations are indicative of tissue inflammation and neoplasia. However, there are no large-sample, real-world studies assessing the levels of serum carbohydrate antigen 125 (CA125) in patients with acute pancreatitis (AP). We aimed to identify the association between elevated CA125 levels and adverse clinical outcomes in AP. METHODS: This was a retrospective cohort study with an analysis of 3939 patients with AP who were admitted to the First Affiliated Hospital of Nanchang University between January 2015 and September 2019 that used data from a prospectively maintained database. Multivariate logistic regression analysis and a propensity score-matched analysis were conducted to reveal the relationship between elevated CA125 levels and poor prognosis. RESULTS: The overall prevalence of elevated CA125 (>35 U/mL) levels was 38.51% (1517/3939) in AP patients. Elevated CA125 levels were independently associated with higher risks of mortality (adjusted odds ratio (AdjOR), 1.82; 95% confidence interval (CI), 1.30-2.54; P < 0.001), severe acute pancreatitis (SAP) (AdjOR, 2.40; 95% CI, 2.00-2.88; P < 0.001), and infected pancreatic necrosis (IPN) (AdjOR, 3.54; 95% CI, 2.65-4.71; P < 0.001). The propensity score-matched cohort analysis also demonstrated that mortality (OR, 1.57; 95% CI, 1.06-2.23; P < 0.05), SAP (OR, 2.20; 95% CI, 1.77-2.73; P < 0.001), and IPN (OR, 2.79; 95% CI, 1.98-3.92; P < 0.001) were more common in the elevated CA125 group than in the normal CA125 group. CONCLUSIONS: Elevated CA125 levels (>35 U/mL) are independently associated with adverse clinical outcomes in AP patients. These observations justify ongoing efforts to understand the role of CA125 in the pathogenesis and prognosis of AP.

Microenvironment-sensitive iridium(iii) complexes for disease theranostics.

Microenvironmental parameters, including hypoxia, pH, polarity, viscosity and temperature, play pivotal roles in controlling the biological, physical or chemical behaviors of local molecules. Abnormal changes in these parameters would cause cellular malfunction or become a hallmark of the occurrence of severe diseases. Recently, a number of phosphorescent Ir(iii) complexes have been designed to respond to such parameters due to their attractive properties such as high photostability, long emission lifetimes, and environment-sensitive emission profiles. This review aims to provide a summary of the progress achieved in developing iridium-based probes responding to microenvironmental parameters in biological systems in recent years for diagnosis and treatment of diseases such as cancer and diabetes.

Integrative Analysis of Differential lncRNA/mRNA Expression Profiling in Helicobacter pylori Infection-Associated Gastric Carcinogenesis.

Helicobacter pylori (H. pylori) infection is the greatest known risk factor for gastric cancer (GC). Long non-coding RNAs (lncRNAs) are implicated in multiple biological processes. However, their contribution in H. pylori-associated GC remains largely unknown. We performed transcriptome sequencing to investigate differential lncRNA and mRNA expression profiles in gastric AGS cells infected with the H. pylori strain 7.13 or 43504. We identified significantly differentially expressed (SDE) mRNAs and lncRNAs following H. pylori infection. A co-expression network of lncRNAs and mRNAs was constructed via WGCNA analysis. Moreover, several of the most significantly upregulated genes were selected for further validation by qRT-PCR analysis in H. pylori-infected gastric cells and transgenic INS-GAS mice. We finally evaluated these genes in human GC tissues. A total of 158442 genes were identified between uninfected and infected cells. Of these, 298 mRNAs and 73 lncRNAs were consistently differentially expressed following infection with the H. pylori 7.13 and 43504 strains, respectively. The expression levels of most upregulated mRNAs (DDIT4, NDRG1, CHAC1, IL32, RELB, CTH, and SLC7A1) and lncRNAs (lncRNA36068, lncRNA51663, lncRNA49853, lncRNA49852, and FLJ46906) were validated by qRT-PCR analysis. We found that H. pylori infection significantly induced the transcript levels of the coding genes RELB and SLC7A11 in in vitro and in vivo assays, which was supported by their high expression levels in GC tissues. In addition, lncRNA51663 and FLJ46906 were remarkably increased in H. pylori-infected cells and consistently overexpressed in human GC tissues compared to adjacent normal tissues. Our study identified mRNA and lncRNA expression profiles related to H. pylori infection. These results may provide important insights regarding lncRNAs in H. pylori-induced gastric carcinogenesis.

RACK1 Acts as a Potential Tumor Promoter in Colorectal Cancer.

BACKGROUND: The receptor of activated protein kinase C 1 (RACK1) promotes the progression and invasion of several cancers. However, the role of RACK1 in the pathogenesis of colorectal cancer (CRC) has not been clearly defined. Herein, we aimed to investigate the biological role of RACK1 in CRC. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset were searched, and the expression of RACK1 in CRC tissues and adjacent normal tissues was evaluated. Immunohistochemical staining was performed to detect the expression of RACK1 in human CRC, adenoma, and normal tissues. Western blotting was used to detect the expression of RACK1 in human CRC cell lines. Functional assays, such as BrdU, colony formation, and wound healing and transwell invasion assays, were used to explore the biological role of RACK1 in CRC. RESULTS: RACK1 was upregulated in CRC tissues compared with its expression in adjacent normal tissues in TCGA and the GEO dataset (P < 0.05). Moreover, RACK1 was significantly overexpressed in CRC and adenoma tissues compared with its expression in normal tissues (P < 0.05). Loss-of-function experiments showed that RACK1 promoted cell proliferation, migration, and invasion in vitro. CONCLUSIONS: Our data indicated that RACK1, as an oncogene, markedly promoted the progression of CRC, which suggested that RACK1 is a potential therapeutic target for CRC management.

Impact factors that modulate gastric cancer risk in Helicobacter pylori-infected rodent models.

Gastric cancer causes a large social and economic burden to humans. Helicobacter pylori (H pylori) infection is a major risk factor for distal gastric cancer. Detailed elucidation of H pylori pathogenesis is significant for the prevention and treatment of gastric cancer. Animal models of H pylori-induced gastric cancer have provided an invaluable resource to help elucidate the mechanisms of H pylori-induced carcinogenesis as well as the interaction between host and the bacterium. Rodent models are commonly used to study H pylori infection because H pylori-induced pathological processes in the stomachs of rodents are similar to those in the stomachs of humans. The risk of gastric cancer in H pylori-infected animal models is greatly dependent on host factors, bacterial determinants, environmental factors, and microbiota. However, the related mechanisms and the effects of the interactions among these impact factors on gastric carcinogenesis remain unclear. In this review, we summarize the impact factors mediating gastric cancer risk when establishing H pylori-infected animal models. Clarifying these factors and their potential interactions will provide insights to construct animal models of gastric cancer and investigate the in-depth mechanisms of H pylori pathogenesis, which might contribute to the management of H pylori-associated gastric diseases.

Downregulation of tumor suppressor RACK1 by Helicobacter pylori infection promotes gastric carcinogenesis through the integrin ß-1/NF-κB signaling pathway.

Receptor of activated protein kinase C 1 (RACK1) is downregulated in gastric cancer and is involved in modulating NF-κB signaling pathway activity. However, the underlying molecular mechanisms regulating RACK1 expression are unclear. In this study, we demonstrated that downregulated expression of RACK1 was observed in gastric cancer tissue compared to adjacent normal tissue and was correlated with poor prognosis in patients. Helicobacter pylori (H. pylori) infection downregulated RACK1 expression in concert with canonical NF-κB signaling pathway activation in vivo and in vitro. RACK1 overexpression suppressed NF-κB signaling pathway activation as well as the release of downstream proinflammatory cytokines. In addition, RACK1 downregulation increased integrin ß-1 expression, while integrin ß-1 silencing decreased NF-κB signaling activation. Moreover, H. pylori infection downregulated RACK1 but upregulated integrin ß-1 expression at the precancerous lesion stages in human subjects. Our data indicate that H. pylori infection promotes the upregulation of integrin ß-1 expression via downregulation of RACK1 expression, which subsequently leads to the elevated activation of the NF-κB signaling pathway, an essential step in H. pylori-induced carcinogenesis.

Analysis of key genes and signaling pathways involved in Helicobacter pylori-associated gastric cancer based on The Cancer Genome Atlas database and RNA sequencing data.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with the development of gastric cancer, although the mechanism is unclear. Herein, this study aimed to clarify the key genes and signaling pathways involved in H. pylori pathogenesis based on The Cancer Genome Atlas (TCGA) database and RNA sequencing analysis. MATERIALS AND METHODS: Forty-nine gastric cancer samples (16 with H. pylori and 33 without H. pylori) and 35 cancer-adjacent normal samples from TCGA database were analyzed by bioinformatics. The differentially expressed genes between H. pylori-positive and H. pylori-negative patients were verified in 18 gastric cancer (GC) samples (9 with H. pylori and 9 without H. pylori), which were analyzed using RNA sequencing. Survival analysis was carried out to explore associations between the differentially expressed genes and prognosis. Bioinformatics analysis was performed to determine the signaling pathways associated with H. pylori. RESULTS: The baseline level of clinical features from TCGA database and RNA sequencing showed no differences between the H. pylori-positive and H. pylori-negative GC groups (P > 0.05). TP53 was shown to be upregulated in the H. pylori-positive group in both TCGA database and RNA sequencing data, which also showed higher expression in the GC tissues than in adjacent normal tissues (P < 0.05). CCDC151, CHRNB2, GMPR2, HDGFRP2, and VSTM2L were shown to be downregulated in the H. pylori-positive group by both TCGA database and RNA sequencing, which also showed lower expression in the GC tissues than in adjacent normal tissues (P < 0.05). GC patients with low expression levels of HDGFRP2 had a poor prognosis (P < 0.05). Thirty-three signaling pathways and 10 biological processes were found to be positively associated with H. pylori infection (P < 0.05, FDR < 0.05). CONCLUSIONS: These results indicate that some genes (TP53, CCDC151, CHRNB2, GMPR2, HDGFRP2, VSTM2L) and previously unidentified signaling pathways (eg, the Hippo signaling pathway) might play an important role in H. pylori-associated GC.

The effect of antioxidants on Helicobacter pylori eradication: A systematic review with meta-analysis.

BACKGROUND: The efficacy and safety of the addition of antioxidants to triple or quadruple therapy were unclear. MATERIALS AND METHODS: This systematic review was performed in accordance with the PRISMA 2009 guidelines. A systematic search of PubMed, EMBASE, and the Cochrane Library databases was conducted to identify potentially relevant publications using the following keywords: ([Helicobacter pylori] or [H. pylori] or [Hp]) and ([antioxidant] or [vitamin] or [N-acetylcysteine] or [curcumin] or [cranberry]). The primary end-point of this study was to evaluate the efficacy of the addition of antioxidants to triple or quadruple therapy according to ITT and PP analysis. The second end-points were side effects and the comparative efficacy in terms of H. pylori eradication according to different antioxidant and antibiotic combinations. RESULTS: We included 9 studies with 1260 participants. The total eradication rate of H. pylori in the group combining eradication therapy with antioxidants was not superior to that without antioxidants according to the ITT (pooled RR [95% CI] = 1.17 [0.99-1.38]; P = 0.07) and PP analysis (pooled RR [95% CI] = 1.15 [0.99-1.34; P = 0.07]. There were no differences regarding side effects between the two groups (pooled RR [95% CI], 1.36 [0.81-2.28]; P = 0.24). However, the eradication regimen with vitamin supplementation (1400 mg/day) showed a significant, superior efficacy in eradication relative to those without supplementation (pooled RR [95% CI] = 1.57 [1.35, 1.84]; P < 0.01). In particular, in the amoxicillin-clarithromycin-based subgroup, the crude H. pylori eradication rate determined by ITT analysis was 81.3% and 68.6% for eradication therapy with and without antioxidant supplementation, respectively, which was a statistically significant difference (pooled RR [95% CI] = 1.23 [1.02-1.49]; P = 0.03). CONCLUSIONS: The addition of antioxidants (vitamin, N-acetylcysteine, curcumin, cranberry) to amoxicillin-clarithromycin-based therapy could improve the eradication rate, and vitamin supplementation might be effective at a high dosage. However, antioxidant supplements have no impact on improving side effects.

Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection.

BACKGROUND: Since the 'Fourth Chinese National Consensus Report on the management of H. pylori infection' was published in 2012, three important consensuses (Kyoto global consensus report on H. pylori gastritis, The Toronto Consensus for the Treatment of H. pylori Infection in Adults and Management of H. pylori infection-the Maastricht V/Florence Consensus Report) have been published regarding the management of H. pylori infection. MATERIALS AND METHODS: A Delphi method was adopted to develop the consensus of relevant 'statements'. First, the established 'statements' were sent to experts via email. Second, after undergoing two rounds of consultation, the initial statements were discussed face to face and revised in the conference item by item on 16 December 2016. Finally, 21 core members of conferees participated in the final vote of statements. Voting for each statement was performed using an electronic system with levels of agreements shown on the screen in real time. RESULTS: Consensus contents contained a total of 48 "statements" and related 6 parts, including indications for H. pylori eradication, diagnosis, treatment, H. pylori and gastric cancer, H. pylori infection in special populations, H. pylori and gastrointestinal microbiota. CONCLUSIONS: Recommendations are provided on the basis of the best available evidence.

Establishment and Characterization of a Nude Mouse Model of Subcutaneously Implanted Tumors and Abdominal Metastasis in Gastric Cancer.

A mouse gastric cancer model is an important tool for studying the mechanisms of gastric cancer. To establish subcutaneously implanted tumors, MKN-45 cell suspensions and tumor tissues were implanted into the middle of the right armpit of nude mice. To generate an abdominal metastasis model, MKN-45 cell suspensions and tumor tissue homogenates were implanted into the middle of the lower abdomen. We measured the weights of the nude mice and the longest dimension, shortest dimension, thickness, and volume of the tumor. We also analyzed the rate of tumor formation, the time required for tumor formation, and the number and size of abdominal tumors in the mice. The rates of formation of the subcutaneously implanted tumors were 100%, 0%, and 100% in the nude mice inoculated with 2 × 107 cells/mL or 1 × 107 cells/mL of the MKN-45 cell suspension or the tumor tissue homogenate (2 × 107 cells/mL), respectively. The rates of metastatic abdominal tumor formation were 100%, 50%, and 75% in mice inoculated with 5 × 107 cells/mL or 1 × 107 cells/mL of the tumor tissue homogenate or the MKN-45 cell suspension (5 × 107 cells/mL), respectively. We derived tumor tissues and tumor tissue homogenates from nude mice prior to establishing the subcutaneous model of implanted tumors and the abdominal metastasis model of gastric cancer, respectively.