[Hyper-IgE syndrome in adults characterized by disseminated mixed infection: a case report and literature review].

Objective: To improve the awareness of hyper-IgE syndrome (HIES) characterized by disseminated infection. Methods: We retrospectively analyzed a patient with HIES characterized by Talaromyces marneffei and Staphylococcus aureus mixed disseminated infection in Shenzhen People's Hospital. The clinical manifestations, results of laboratory tests/genetic examinations, therapeutic strategies and prognosis were summarized. The keywords "hyper-lgE syndrome" were used to search and review the literature in Wanfang databases and Pubmed database. Results: In February 2021, an 18-year-old male patient was admitted to our hospital with backache for over 3 weeks and fever for 4 days. Physical examination revealed deciduous teeth in the oral cavity, bilateral renal pain on percussion, and interphalangeal joint hyperextension. Laboratory studies demonstrated increased blood eosinophils and serum level of total IgE. Bacterial culture from bronchoscopic secretions, bronchial mucosa, and necrotic tissue from the left upper arm showed Talaromyces marneffei. Bacterial culture from alveolar lavage fluid, left upper arm necrotic tissue, puncture fluid of right retroauricular abscess and renal drainage fluid suggested methicillin-sensitive Staphylococcus aureus. The chest and abdominal CT revealed diffuse patchy and nodular lesions in bilateral lungs, cavitary lesions in the upper lobe of the left lung, multiple enlarged lymph nodes in the mediastinum, and infectious lesions within both kidneys and perirenal space. Furthermore, the patients was identified with STAT3 mutations by whole exome sequencing, which confirmed the diagnosis of HIES. Nineteen literature articles were retrieved, involving 27 adult patients with a median age of diagnosis of 23 years. The most common manifestations included: skin infection (16/27), eczema (15/27), elevated IgE (26/27) and eosinophils (17/27), as well as positive STAT3 mutation (11/27). Conclusion: Clinicians should be alert to the possibility of hyper-IgE syndrome in patients with severe or disseminated intracellular bacterial infections.

[Clinical analysis of 3 cases of eosinophilic granulomatosis with polyangiitis].

Objective: To improve the clinical recognition of eosinophilic granulomatosis with polyangiitis(EGPA) in clinical manifestations, diagnosis and treatment. Methods: The clinical manifestations, pathological characteristic, imaging manifestations, diagnosis and the therapy of three patients with EGPA were presented. Results: These 3 patients had asthma-like symptoms and extrapulmonary manifestations of systemic vasculitis. They were 20, 40 and 44 years old. All of them were female.They denied exposure or contact. Chest radiographic examination showed that the most common features were nodule shadow and tree-in-bud in the lung. The pathological manifestation was characterized by hypereosinophilia, high total IgE(over 300 KU/L) and high CRP(over 14.1mg/L). The FeNO of 2 patients was over 100ppb. The ANCA of these 3 patients was negative. The pulmonary pathology was observed had eosinophil infiltration in the alveolar, interstitial and vessel for 3 cases. The clinical manifestations were nonspecific. All patients were treated by glucocorticoid and immune-inhibitor(alkylating agents or purine synthesis inhibitors) therapy. Because patients were complicated with other organs involved, they needed long-time treatment. Conclusions: This disease is diverse and complex, with a lack of pathognomonic symptoms. We should highly suspect eosinophilic granulomatosis with polyangiitis, when the patients present severe asthma and eosinophilia. Early detection, early treatment, and the prognosis could be better.

Hepatitis B virus infection is associated with gastric cancer in China: an endemic area of both diseases.

BACKGROUND: Hepatitis B virus (HBV) infection was demonstrated to be a risk factor of several cancers of the digestive system. In addition, liver cirrhosis, which could possibly result from chronic HBV infection, was associated with a higher risk of gastric cancer. However, the association of HBV infection and gastric cancer has not been investigated. METHODS: A retrospective case-control study with 580 cases and 580 controls matched for age, sex and year of diagnosis was conducted. The associations between gastric cancer and HBV infection were explored with univariate and multivariate unconditional logistic regression analysis. RESULTS: Hepatitis B surface antigen (HBsAg) was positively associated with gastric cancer (AOR (95% CI): 1.49 (1.06-2.10)). This association remained significant in patients without family history of gastric cancer (AOR (95% CI): (1.06-2.11)). For HBsAg-negative population, being anti-HBc positive/anti-HBs negative, which possibly indicated occult HBV infection, was also found to have some associations with gastric cancer. In addition, some synergistic effects between HBV infection and blood type A in gastric cancer were identified. CONCLUSIONS: The HBV infection was positively related with gastric cancer, especially for patients without family history of gastric cancer. Further prospective studies are warranted to confirm this relationship.

Pemetrexed for previously treated patients with metastatic gastric cancer: a prospective phase II study.

BACKGROUND: Gastric cancer is one of the leading causes of cancer-related death worldwide. There were debates on the value of the second-line and beyond chemotherapy by the time we designed this trial. So we designed this phase II trial to assess the efficacy and safety of pemetrexed in patients with pretreated metastatic gastric cancer. METHODS: Thirty-four patients with pretreated metastatic gastric cancer were enroled in the study. Patients received pemetrexed 500 mg m(-2) every 21 days until the presence of progressive disease (PD) or unacceptable toxicity. RESULTS: A total of 34 patients were enroled in the study; 34 were eligible for toxicity and 30 for response. The response rate was 13.3%, 13.3% patients achieved a partial response, 50.0% achieved stable disease and 36.7% had a PD as the best response. The median overall survival time and median progression-free survival time was 6.4 months (95% confidence interval (CI) 5.8-9.5 months) and 2.2 months (95% CI 2.0-5.5 months), respectively. Most haematologic and non-haematologic toxicity were grade 1/2. Grade 3/4 toxicity included fatigue, neutropenia, thrombocytopenia, weight loss, anorexia and transaminase elevation. CONCLUSIONS: The monochemotherapy of pemetrexed is active and well tolerated when used in previously treated patients with metastatic gastric cancer.

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo.

Epidermal growth factor receptor (EGFR) had been reported as one of the major responsible genes for malignant progression and phenotype reversion of gliomas, and has been used as one of the most important therapeutic targets. In the present study, small interference RNA (siRNA) and antisense EGFR expression constructs, which target sequences of human EGFR catalytic domain (2400-2420) and the 3'-coding region, respectively, were used to examine the growth inhibition effects on U251 glioma cells. Cell growth was significantly inhibited and G2/M arrest was observed in antisense- and siRNA-treated groups. Matrigel matrix demonstrated spotted cell clustering pattern in antisense- and siRNA-transfected U251 cells, indicating poor cell growth activities. In addition, the tumor volumes in U251 subcutaneous mice model treated with antisense and siRNA were significantly smaller than those treated with control siRNA and phosphate-buffered saline. Also, glial fibrillary acidic protein expression was upregulated in antisense- and siRNA-treated groups than the control groups. Our results demonstrated that antisense- or siRNA-targeting intracellular region of EGFR can inhibit EGFR expression, exerted growth inhibition effect on U251 glioma cells in vitro and in vivo. Consequently, siRNA expression plasmid-mediated gene therapy would be a new strategy in treatment of gliomas.