Case report: Acute Talaromyces marneffei mediastinitis in an HIV-negative patient.

Talaromyces marneffei (T. marneffei) is one of the most important opportunistic human pathogens endemic in Southeast Asia. Talaromycosis, which was once regarded as an opportunistic infectious disease in patients with acquired immunodeficiency syndrome, is being increasingly reported in HIV-negative populations. Since T. marneffei infection can be localized or disseminated, patients may present with a variety of symptoms. However, mediastinal infection attributed to T. marneffei is extremely rare. We report the case of a 32-year-old female who manifested a large mediastinal mass and was eventually diagnosed as acute T. marneffei mediastinitis. The patient was HIV-negative and had no direct contact with intermediate hosts. We successfully managed to treat the patient with inhaled amphotericin B deoxycholate and observed lesion absorption in subsequent CT examinations. To our knowledge, this is the first published case of T. marneffei mediastinitis and first use of inhaled antifungal monotherapy on patients with T. marneffei infection.

Comparative study on the mutation spectrum of tissue DNA and blood ctDNA in patients with non-small cell lung cancer.

Background: To study the mutations detected in tissue DNA and blood circulating tumor DNA (ctDNA) of patients with advanced lung cancer and analyze the correlations between gene mutations, clinical features, and treatment. Methods: Targeted next-generation sequencing (NGS) technology based on probe hybrid capture and Illumina high-throughput sequencing was used to detect the DNA of tumor tissue samples (n=24) and blood samples (n=15) of ctDNA from 28 lung cancer patients with a clear pathological diagnosis. For mutations, the detection range included 4 types of mutations (point mutations, small indels, copy number variations) in all exon regions and partial intron regions of the 556 genes panel. Results: The most frequently detected mutant genes in 24 lung cancer tissue samples were TP53 (58.3%, 14/24), EGFR (33.3%, 8/24), LRP1B (25.0%, 6/24), KRAS (20.8%, 5/24), and ARID1A (16.7%, 4/24). The common mutant genes detected in 15 ctDNA samples were TP53 (60%, 5/15), EGFR (33.3%, 5/15), LRP1B (20.0%, 3/15), ERBB4 (3/15), and ARID1A (13.3%, 2/15). Among the 28 patients, 11 patients underwent both tissue DNA and ctDNA detection. The average co-mutation frequency of paired tissue DNA with ctDNA was 38.9% (0-83.3%), and the median value was 37.5%. Conclusions: Tissue DNA and ctDNA samples could detect genetic mutations and be consistent. Therefore, ctDNA detection as a method for disease diagnosis and evaluation of tumor molecular status may be helpful for the clinical diagnosis and treatment of lung cancer patients.

DNA-methylation-induced silencing of DIO3OS drives non-small cell lung cancer progression via activating hnRNPK-MYC-CDC25A axis.

DNA methylation is a class of epigenetic modification manner, which is responsible for the inactivation of various tumor suppressors. Recently, long non-coding RNAs (lncRNAs) were revealed to be implicated in a variety of malignancies, including non-small cell lung cancer (NSCLC). However, the contributions of lncRNAs to DNA-methylation-induced oncogenic effects in NSCLC remain largely unknown. In this study, we identified a DNA-methylation-repressed lncRNA DIO3 opposite strand upstream RNA (DIO3OS) in NSCLC. DIO3OS is downregulated in NSCLC, and its low expression is related to poor prognosis. Ectopic expression of DIO3OS repressed NSCLC cell growth and motility and promoted NSCLC cell apoptosis in vitro. DIO3OS also repressed NSCLC tumorigenesis and metastasis in vivo. DIO3OS knockdown exhibited opposite biological effects. DIO3OS competitively bound heterogeneous nuclear ribonucleoprotein K (hnRNPK), repressed the binding of hnRNPK to MYC DNA and MYC mRNA, reduced the promoting roles of hnRNPK on MYC transcription and translation, led to the repression of MYC transcription and translation, and therefore remarkably decreased the expression of MYC and CDC25A, a downstream target of MYC. Additionally, depletion of hnRNPK blocked the tumor-suppressive roles of DIO3OS in NSCLC. In conclusion, these findings identified DIO3OS as an important protective factor against NSCLC via modulating hnRNPK-MYC-CDC25A axis.

Long non-coding RNA BRE-AS1 represses non-small cell lung cancer cell growth and survival via up-regulating NR4A3.

Recently, several long non-coding RNAs (lncRNAs) have been revealed to play crucial roles in tumorigenesis and progression of many cancers. Nevertheless, more than 50,000 lncRNAs were identified in human cells and the roles of majority of these lncRNAs in non-small cell lung cancer (NSCLC) are unknown. In this study, using public NSCLC microarray data we identified a novel lncRNA BRE antisense RNA 1 (BRE-AS1). BRE-AS1 is significantly down-regulated in NSCLC tissues and cell lines. Gain-of-function and loss-of-function assays showed that BRE-AS1 reduces NSCLC cell viability, represses NSCLC cell proliferation, and induces NSCLC cell apoptosis in vitro, and represses NSCLC tumor growth in vivo. Mechanistic investigation revealed that BRE-AS1 physically binds STAT3, reduces the binding of STAT3 to the promoter of NR4A3, relieves the repression of NR4A3 caused by STAT3, and up-regulates NR4A3 expression. Consistently, NR4A3 is significantly down-regulated in NSCLC tissues and the expression of NR4A3 is positively correlated with the expression of BRE-AS1 in NSCLC tissues. In addition, depletion of NR4A3 attenuates the tumor suppressive roles of BRE-AS1 in NSCLC. Collectively, our data demonstrate that BRE-AS1 represses NSCLC cell growth and survival via up-regulating NR4A3 and suggest that enhancing BRE-AS1 may be potential therapeutic strategy for NSCLC.

[Clinical analysis of 190 cases of outbreak with atypical pneumonia in Guangzhou in spring, 2003].

OBJECTIVE: To study methods of diagnosis and treatment for atypical pneumonia (Severe Acute Respiratory Syndrome), outbreak of the illness in Guangzhou during Jan. - Mar., 2003. METHODS: 190 cases with atypical pneumonia were analyzed, and the cases were admitted in Guangzhou municipal First Hospital and Guangzhou municipal Eighth Hospital. RESULTS: Patients were infected by close quarters contacting each other. All patients manifest high fever, and accompany by dyspnea, cough, palpitate, weakness, headache and swirl. Other 46 cases were accompanied by diarrhea. Most of patients, manifestation of lungs was negative. Chest X-ray, shadow of lungs were light in beginning, and change to severity slowly or suddenly during 5 - 10 days. Of these cases, 36 cases develop to ARDS and 11 cases died with severity ARDS. Using general antibiotic was of no effect for the illness. Continual positive airway pressure (CPAP) and glucocorticoid was required that can control deprivation of the disease when toxicosis symptom of patients was severity and shadow of lungs diffuse more and more. CONCLUSION: Infectivity of the illness is evidence and spread by airway. Using general antibiotic was of no effect for the illness. Continual positive airway pressure (CPAP) and glucocorticoid are effective for control of the disease.