Type I and type II Helicobacter pylori infection status and their impact on gastrin and pepsinogen level in a gastric cancer prevalent area.

BACKGROUND: Type I Helicobacter pylori (H. pylori) infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis. However, its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated; it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17 (G-17) and pepsinogens (PGs) during clinical practice. AIM: To explore the prevalence of type I and type II H. pylori infection status and their impact on G-17 and PG levels in clinical practice. METHODS: Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined, and 523 patients were enrolled in this study. H. pylori infection was confirmed by both 13C-urea breath test and serological assay. Patients were divided into non-atrophic gastritis (NAG), non-atrophic gastritis with erosion (NAGE), chronic atrophic gastritis (CAG), peptic ulcers (PU) and gastric cancer (GC) groups. Their serological G-17, PG I and PG II values and PG I/PG II ratio were also measured. RESULTS: A total H. pylori infection rate of 3572 examined patients was 75.9%, the infection rate of 523 enrolled patients was 76.9%, among which type I H. pylori infection accounted for 72.4% (291/402) and type II was 27.6%; 88.4% of GC patients were H. pylori positive, and 84.2% of them were type I infection, only 11.6% of GC patients were H. pylori negative. Infection rates of type I H. pylori in NAG, NAGE, CAG, PU and GC groups were 67.9%, 62.7%, 79.7%, 77.6% and 84.2%, respectively. H. pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio. Both types of H. pylori induced higher G-17 level, but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG, NAGE and CAG groups over uninfected controls. Overall PG I levels showed no difference among all disease groups and in the presence or absence of H. pylori; in stratified analysis, its level was increased in GC and PU patients in H. pylori and type I H. pylori-positive groups. CONCLUSION: Type I H. pylori infection is the major form of infection in this geographic region, and a very low percentage (11.6%) of GC patients are not infected by H. pylori. Both types of H. pylori induce an increase in G-17 level, while type I H. pylori is the major strain that affects PG I and PG IIs level and PG I/PG II ratio in stepwise chronic gastric disease. The data provide insights into H. pylori infection status and indicate the necessity and urgency for bacteria eradication and disease prevention in clinical practice.

Comparison the cost-efficacy of furazolidone-based versus clarithromycin-based quadruple therapy in initial treatment of Helicobacter pylori infection in a variable clarithromycin drug-resistant region, a single-center, prospective, randomized, open-label study.

Helicobacter pylori (Hp) drug resistant rate to clarithromycin (CLA) has increased to 20% to 50%, which cause concerns regarding its effectiveness in eradicating Hp, we aim to evaluate the cost-effectiveness of CLA-based versus furazolidone (FZD)-based quadruple therapy, and assess factors that affect anti-Hp efficacy.One hundred eighty-five patients were enrolled in this single-center, prospective, randomized, open-label study. In FZD group, 92 patients were treated with FZD plus esomeprazole, bismuth potassium citrate, and amoxicillin for 14 days. In CLA group, 93 patients were treated with the same regimen except FZD was replaced by CLA. Patients were tested 4 weeks post-treatment to confirm eradication.Of the 185 enrolled patients, 180 completed the study. On intention-to-treat analysis, Hp eradication rates in FZD and CLA groups were 90.22% and 86.02% (P = .378); in per-protocol analysis, their eradication rates were 93.26% and 87.91%, respectively (P = .220). Overall incidence of total side effects in FZD and CLA groups was 19.57% and 13.98%, and their severe side effects were 3.26% and 2.15%, respectively (P > .05). Cost-effectiveness ratios of FZD and CLA groups were 0.75 and 1.02, and incremental cost-effectiveness ratio of FZD group over CLA group was -3.62. Eradication failures were not associated with factors including gender, age, body mass index, smoking, alcohol consumption, educational level, and urban-rural distribution in this observation (P > .05).Despite increasing drug resistance to CLA, Hp eradication rates in FZD and CLA groups have no significant difference at present; as FZD-based quadruple therapy is more cost-effective, we recommend this regimen be a first-line choice for Hp eradication.

Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis.

AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis. METHODS: A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period. RESULTS: Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 10(9)/L vs 63.3 ± 15.7 × 10(9)/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation. CONCLUSION: BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.

Anti-apoptotic proteins and catalase-dependent apoptosis resistance in nickel chloride-transformed human lung epithelial cells.

Chronic exposure to nickel compounds is associated with increased incidence of certain types of human cancer, including lung and nasal cancers. Despite intensive investigation, the oncogenic processes remain poorly understood. Apoptosis resistance is a key feature for tumor cells to escape physiological surveillance and acquire growth advantage over normal cells. Although NiCl2 exposure induces transformation of human lung epithelial cells, little information is available with regard to its molecular mechanisms, it is also not clear if the transformed cells are apoptosis resistant and tumorigenic. We explored the apoptosis resistance properties of nickel chloride­transformed human lung epithelial cells and the underlying mechanisms. The results showed that transformed BEAS-2B human lung epithelial cells are resistant to NiCl2-induced apoptosis. They have increased Bcl-2, Bcl-xL and catalase protein levels over the passage matched non­transformed counterparts. The mechanisms of apoptosis resistance are mitochondria­mediated and caspase-dependent. Forced overexpression of Bcl-2, Bcl-xL and catalase proteins reduced NiCl2-induced cell death; siRNA­mediated knockdown of their expression sensitized the cells to nickel-induced apoptosis, suggesting that Bcl-2, Bcl-xl and catalase protein expression plays a critical role in apoptosis resistance. Akt also participates in this process, as its overexpression increases Bcl-xL protein expression levels and attenuates NiCl2-induced apoptosis. Furthermore, transformed cells are tumorigenic in a xenograft model. Together, these results demonstrate that nickel-transformed cells are apoptosis­resistant and tumorigenic. Increased expression of Bcl-2, Bcl-xL and catalase proteins are important mechanisms contributing to transformed cell oncogenic properties.

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.

[Serum proteomic profiles of the subjects with esophageal precancerous and cancerous lesions from Linzhou, an area with high incidence of esophageal cancer in Henan Province, Northern China].

BACKGROUND & OBJECTIVE: Some molecular changes occurred in esophageal precancerous and cancerous lesions could be reflected in the serum, but the clinical application is limited because of their low sensitivity and specificity. Serum proteomic profiling is much desirable in identifying the proteins closely related to esophageal carcinogenesis. This study was to characterize the serum protein profiles of the subjects with normal esophagus, esophageal precancerous and cancerous lesions from Linzhou, the area with the highest incidence of esophageal carcinoma (EC) in Henan Province, Northern China. METHODS: Proteomic spectra were generated with surface-enhanced laser desorption/inionation-time of flight-mass spectra (SELDI-TOF-MS) and weak cation exchange (WCX2) protein chip system, and analyzed by bioinformatics like decision tree classification algorithm on a set of serum from 130 symptom-free subjects [including 63 cases with normal esophageal epithelia, 40 with basal cell hyperplasia (BCH), and 27 with dysplasia (DYS)] and 30 EC patients from Linzhou. RESULTS: One protein in BCH group with a ratio of mass to charge (M/Z) of M9 306.61 u, 1 in DYS group with a M/Z ratio of M13 765.9 u, and 2 in EC group with M/Z ratios of M2 942.15 u and M15 953.4 u were selected to build 3 decision tree classification models to identify the subjects with BCH, DYS, and EC, respectively. With these classification models, the sensitivities of identifying BCH, DYS and EC were 57.5% (23/40), 88.8% (24/27) and 96.6% (29/30), respectively, in the training sets, and 57.5% (23/40), 66.6% (18/27) and 60.0% (18/30), respectively, in the test sets; the specificities of identifying BCH, DYS and EC were 96.8% (61/63), 63.4% (40/63) and 92.0% (58/63), respectively, in the training sets, and 95.2% (60/63), 71.4% (45/63) and 84.1% (53/63), respectively, in the test sets. CONCLUSION: The protein sets with M/Z ratios of M9 306.61 u, M13 765.9 u, M2 942.15 u, and M15 953.4 u may contain promising serum biomarkers for screening the subjects with high-risk of EC.

[The application of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in diagnosing dysplasia and chronic atrophic gastric-carditis in population with high risk of gastric-cardia adenocarcinoma].

OBJECTIVES: To evaluate the serum biomarkers for diagnosis of gastric cardia dysplasia (DYS) and chronic atrophic gastric-carditis (CAG) and to provide a novel screening method for high risk population of gastric-cardia adenocarcinoma (GCA). METHODS: Proteomic spectra were generated by surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS) and weak cation exchange protein chip system. A set of spectra derived from analysis of serum from 143 symptom-free subjects at high-risk area for GCA, including 63 cases with histologically normal gastric cardia epithelia, 57 of CAG and 23 of DYS, were analyzed by bioinformatics like decision tree classification algorithm. The sensitivity and the specificity for test group were performed by using 10-fold cross validation classification with the decision tree classification model. RESULTS: One protein spot with a ratio of mass to charge (M/Z) of M3894. 0 was selected to build a decision tree classification model to identify the case with DYS or normal. With this classification model, the sensitive rate for DYS identification was 87% (20/23). Two proteins with M/Z of M2942. 15 and M33316. 6 were used to build a decision tree classification model. With this model, the sensitivity for discriminating CAG from normal was 93% (53/57) and the specificity was 92 (58/63). CONCLUSIONS: The gastric cardia lesions of DYS and CAG could be identified by SELDI-TOF-MS technique specifically in symptom-free subjects at high incidence area for GCA. The present findings provide a new screening way for high-risk subjects with CGA.