for the China Gastric Cancer Study Group T HE ASSOCIATION BETWEEN chronic Helicobacter pylori infection and development of gastric cancer is well established. [1][2][3][4] The International Agency for Research on Cancer has categorized H pylori as a group I carcinogen. 5 In Correa's model of gastric carcinogenesis, the gastric mucosa progresses through the stages of chronic active gastritis, glandular atrophy, intestinal metaplasia, and dysplasia before the development of gastric adenocarcinoma. 6-10 Two recent large-scale, prospective studies, 11,12 both in high-risk populations, have re-ported H pylori infection as a definite risk factor for the development of gastric cancer. In the first study, presence of H pylori at baseline was associated with an increased risk of progression to dyspla-Author Affiliations and Members of the China Gastric Cancer Study Group are listed at the end of this article.

Purpose: Studies have shown that mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain are associated with response of lung cancer to gefitinib (Iressa, AstraZeneca Corp., Shanghai, China). A higher incidence of EGFR mutation was observed in non^small cell lung cancer (NSCLC) patients of Japanese origin compared with those of American origin. However, no data about such mutations in Chinese patients with NSCLC could be obtained. Methods: Primary NSCLC tissues were obtained for analysis of mutations in exons 18 to 21 of EGFR from a total of 76 patients, of whom 54 did not receive gefitinib therapy and 22 did. PCR products were sequenced directly and mutations were confirmed by an independent PCR and sequence analysis. All types of mutation were cloned and sequenced. Results: A total of 10 types of mutation were found in the series of patients, including two different silent mutations in exon 20 from 11patients. More than half of the silent mutations (6 of 11) in exon 20 coexisted with other mutations. Mutations were more frequent in adenocarcinoma (17 of 35; 48.6%) compared with squamous carcinoma (1 of 19; 5.3%) among untreated patients. Similar mutations were observed in all seven gefitinib-treated patients with partial response, and no mutations were detected in all eight patients with progressive disease (P < 0.001), except two silent mutations. Three mutations were observed in seven patients with stable disease. Conclusions: Mutations in the epidermal growth factor receptor tyrosine kinase domain in lung adenocarcinomas from Chinese patients were more frequent than reported previously in lung adenocarcinomas from American patients. Such mutations were well correlated with tumor response to gefitinib.

BackgroundHeart failure (HF) is a progressive disorder characterized by reduced cardiac output and increased peripheral resistance, ultimately leading to tissue perfusion deficits and devastating consequences for several organs including the brain. We previously described a tumor necrosis factor-α (TNF-α)–dependent enhancement of posterior cerebral artery tone and concomitant reduced cerebral blood flow in a mouse model of early HF in which blood pressure remains minimally affected. HF is often associated with cognitive impairments such as memory deficits, even before any overt changes in brain structure and function occur. The pathophysiology underlying the development of cognitive impairments in HF is unknown, and appropriate treatment strategies are lacking.Methods and ResultsWe used a well-established mouse model in which HF was induced by experimental myocardial infarction produced by permanent surgical ligation of the left anterior descending coronary artery (infarct size ≈25% of the left ventricular wall). Ligated mice developed enlarged hearts, congested lungs, and reduced cardiac output and blood pressure, with elevated peripheral resistance within 6 to 8 weeks after ligation. In this study, we demonstrated the significance of the proinflammatory cytokine TNF-α during HF-mediated neuroinflammation and associated impaired hippocampus-independent nonspatial episodic memory function. Augmented cerebral TNF-α expression and microglial activation in HF mice, indicative of brain inflammation, were accompanied by morphological changes and significant reduction of cortical dendritic spines (61.39±8.61% for basal and 61.04±9.18% for apical spines [P<0.001]). The significance of TNF-α signaling during the observed HF-mediated neurodegenerative processes is supported by evidence showing that sequestration or genetic deletion of TNF-α ameliorates the observed reduction of cortical dendritic spines (33.51±7.63% for basal and 30.13±6.98% for apical spines in wild-type mice treated with etanercept; 17.09±6.81% for basal and 17.21±7.29% for apical spines in TNF-α−/−). Moreover, our data suggest that alterations in cerebral serum and glucocorticoid-inducible kinase 1 (SgK1) expression and phosphorylation during HF may be TNF-α dependent and that an increase of SgK1 phosphorylation potentially plays a role in the HF-associated reduction of dendritic spine density.ConclusionsOur findings demonstrate that TNF-α plays a pivotal role in HF-mediated neuroinflammation and associated alterations of cortical dendritic spine density and has the potential to reveal novel treatment strategies for HF-associated memory deficits.

BackgroundIncreasing cases of diabetes, a general lack of routinely operational prevention, and a long history of separating disease prevention and treatment call for immediate engagement of frontier clinicians. This applies especially to village doctors who work in rural China where the majority of the nation’s vast population lives.ObjectiveThis study aims to develop and test an online Smart Web Aid for Preventing Type 2 Diabetes (SWAP-DM2) capable of addressing major barriers to applying proven interventions and integrating diabetes prevention into routine medical care.MethodsDevelopment of SWAP-DM2 used evolutionary prototyping. The design of the initial system was followed by refinement cycles featuring dynamic interaction between development of practical and effective standardized operation procedures (SOPs) for diabetes prevention and Web-based assistance for implementing the SOPs. The resulting SOPs incorporated proven diabetes prevention practices in a synergetic way. SWAP-DM2 provided support to village doctors ranging from simple educational webpages and record maintenance to relatively sophisticated risk scoring and personalized counseling. Evaluation of SWAP-DM2 used data collected at baseline and 6-month follow-up assessment: (1) audio recordings of service encounters; (2) structured exit surveys of patients’ knowledge, self-efficacy, and satisfaction; (3) measurement of fasting glucose, body mass index, and blood pressure; and (4) qualitative interviews with doctors and patients. Data analysis included (1) descriptive statistics of patients who received SWAP-DM2–assisted prevention and those newly diagnosed with prediabetes and diabetes; (2) comparison of the variables assessed between baseline and follow-up assessment; and (3) narratives of qualitative data.ResultsThe 17 participating village doctors identified 2219 patients with elevated diabetes risk. Of these, 84.85% (1885/2219) consented to a fasting glucose test with 1022 new prediabetes and 113 new diabetes diagnoses made within 6 months. The prediabetic patients showed substantial improvement from baseline to 6-month follow-up in vegetable intake (17.0%, 43/253 vs 88.7%, 205/231), calorie intake (1.6%, 4/253 vs 71.4%, 165/231), leisure-time exercises (6.3%, 16/253 vs 21.2%, 49/231), body weight (mean 62.12 kg, SD 9.85 vs mean 58.33 kg, SD 9.18), and body mass index (mean 24.80 kg/m2, SD 3.21 vs mean 23.36 kg/m2, SD 2.95). The prediabetic patients showed improvement in self-efficacy for modifying diet (mean 5.31, SD 2.81 vs mean 8.53, SD 2.25), increasing physical activities (mean 4.52, SD 3.35 vs mean 8.06, SD 2.38), engaging relatives (mean 3.93, SD 3.54 vs mean 6.93, SD 2.67), and knowledge about diabetes and risks of an imbalanced diet and inadequate physical activity. Most participating doctors and patients viewed SWAP-DM2 as useful and effective.ConclusionsSWAP-DM2 is helpful to village doctors, acceptable to patients, and effective in modifying immediate determinants of diabetes at least in the short term, and may provide a useful sol...

BackgroundThorax is the common place to develop Castleman disease (CD), but there is no systemic clinical analysis for intrathoracic CD.MethodsWe conducted a retrospective analysis of 48 intrathoracic CD patients with definite pathological diagnosis who were hospitalized between 1992 and 2012 in a Chinese tertiary referral hospital.ResultsThe study included 16 cases with unicentric CD (UCD) and 32 cases with multicentric CD (MCD). UCD were younger than MCD (30.5y vs 41.6ys, P < 0.05). MCD were more symptomatic (50% vs 96.9%, P < 0.001) and sicker than UCD, including more fever, hepatomegaly and/or splenomegaly and hypoalbuminemia. All of UCD showed solitary mass in various sites and two of them were complicated by small pleural effusion. In the MCD group, their chest CT showed obvious lymphadenopathy in the hilum and/or mediastinum (100%), diffuse parenchymal lung shadows (43.75%), pleural effusion (40.6%), mass in the mediastinum (6.25%) or hilum (3.12%) and bronchiolitis obliterans (BO) (3.12%). Besides LIP-like images, multiple nodules of different size and sites, patchy, ground-glass opacities and consolidation were showed in their chest CT. Surgery were arranged for all UCD for diagnosis and treatment and all were alive. In MCD group, superficial lymph nodes biopsies (21 cases), surgery biopsy (9 cases) and CT-guided percutaneous lung biopsy (2 cases) were performed. Hyaline vascular (HV) variant were more common in the UCD group (75% vs 37.5%, P < 0.05). In MCD group, 28 cases were prescribed with chemotherapy, one refused to receive therapy and the rest three were arranged for regular follow-up. Among MCD, 18 cases was improved, 7 cases was stable, 4 cases lost follow-up and 3 cases died.ConclusionsIntrathoracic MCD was more common than UCD in our hospital. MCD was older, more symptomic and sicker than UCD. HV variant were more common in UCD. All of UCD showed mass in various intrathoracic locations and surgery resection was performed for all and all were alive. Mass, pleural effusion, BO and diffuse pulmonary shadows, including LIP-like images, multiple nodules of different size and sites, patchy, GGO and consolidations were showed in our MCD. Most of MCD cases were arranged with chemotherapy and their prognosis were worse than UCD’s.