The preventive treatment of latent tuberculosis infection (LTBI) is of great importance for the elimination and control of tuberculosis (TB) worldwide, but existing screening methods for LTBI are still limited in predicting the onset of TB. Previous studies have found that some high-risk factors (including human immunodeficiency virus (HIV), organ transplantation, silicosis, tumor necrosis factor-alpha blockers, close contacts and kidney dialysis) contribute to a significantly increased TB reactivation rate. This article reviews each risk factor's association with TB and approaches to address those factors. Five regimens are currently recommended by the World Health Organization, and no regimen has shown superiority over others. In recent years, studies have gradually narrowed down to the preventive treatment of LTBI for high-risk target groups, such as silicosis patients, organ-transplantation recipients and HIV-infected patients. This review discusses regimens for each target group and compares the efficacy of different regimens. For HIV patients and transplant recipients, isoniazid monotherapy is effective in treating LTBI, but for others, little evidence is available at present.

BackgroundExosomes are small vesicles containing a wide range of functional proteins, mRNA and miRNA. Exosomal miRNAs from cancer cells play crucial roles in mediating cell-cell communication and tumor-microenvironment cross talk, specifically in enabling metastasis and promoting angiogenesis. We focused on miR-9 that was identified as a tumor suppressor previously in nasopharyngeal carcinoma (NPC) tumorigenesis.MethodsDifferential centrifugation, transmission electron microscopy and nanoparticle tracking analysis were used to isolate and identify exosomes. Quantitative PCR and western blotting analysis were used to detect miR-9, pri-miR-9, CD63, TSG101, MDK, P70S6K P-Ser424 and PDK1 P-Ser241 expression. Laser confocal microscopy was used to trace exosomal miR-9 secreted by NPC cells into HUVECs. The effect of exosomal miR-9 on cell migration and tube formation of HUVECs in vivo and vitro was assessed by using migration assay, tube formation assay and matrigel plug assay, respectively. Bioinformatics analysis and luciferase reporter assay were utilized to confirm the binding of exosomal miR-9 to the 3′untranslated region (3′-UTR) of MDK, while Phosphorylation Array was performed to identify AKT Pathway in HUVECs treated with exosomal miR-9. Furthermore, Immunohistochemistry (IHC) and in situ hybridization (ISH) was used to detected miR-9, CD31 and MDK expression in human NPC tumor samples.ResultsNPC cells transfected with miR-9-overexpressing lentivirus, released miR-9 in exosomes. Exosomal miR-9 directly suppressed its target gene - MDK in endothelial cells. Mechanistic analyses revealed that exosomal miR-9 from NPC cells inhibited endothelial tube formation and migration by targeting MDK and regulating PDK/AKT signaling pathway. Additionally, the level of MDK was upregulated in NPC tumor samples and was positively correlated with microvessel density. Notably, the level of exosomal miR-9 was positively correlated with overall survival, and MDK overexpression was positively associated with poor prognosis in NPC patients, suggesting the clinical relevance and prognostic value of exosomal miR-9 and MDK.ConclusionsTaken together, our data identify an extracellular anti-angiogenic role for tumor-derived, exosome-associated miR-9 in NPC tumorigenesis and prompt further investigation into exosome-based therapies for cancer treatment.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0814-3) contains supplementary material, which is available to authorized users.

This study demonstrated a significant increase in TB risk in patients with RA treated with TNF-α antagonists; among them, ETN is least likely to cause active TB. The study also proposes the necessity of LTBI prophylaxis in patients with RA.

BackgroundCancers have a multifactorial etiology a part of which is genetic. Recent data indicate that expression of the tight junction claudin proteins is involved in the etiology and progression of cancer.MethodsTo explore the correlations of the tight junction proteins claudin-2,-6, and −11 in the pathogenesis and clinical behavior of gastric cancer, 40 gastric cancer tissues and 28 samples of non-neoplastic tissues adjacent to the tumors were examined for expression of claudin-2,-6, and −11 by streptavidin-perosidase immunohistochemical staining method.ResultsThe positive expression rates of claudin-2 in gastric cancer tissues and adjacent tissues were 25% and 68% respectively (P < 0.001). The positive expression rates of claudin-6 in gastric cancer tissues and adjacent tissues were 55% and 79% respectively (P = 0.045 < 0.05). In contrast, the positive expression rates of claudin-11 in gastric cancer tissues and gastric cancer adjacent tissues were 80% and 46% (P = 0.004 < 0.01). Thus in our study, the expression of claudin-2, and claudin-6 was down regulated in gastric cancer tissue while the expression of claudin-11 was up regulated. Correlations between claudin expression and clinical behavior were not observed.ConclusionOur study provides the first evidence that claudin-2,-6, and −11 protein expression varies between human gastric cancers and adjacent non-neoplastic tissues.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5470513569630744

A U-shaped external photonic quasi-crystal fiber (PQF) sensor based on surface plasmon resonance is proposed for refractive index (RI) sensing. The advantages of sensing with metal/liquid surface plasmon polariton (SPP) mode are summarized. The gold/liquid SPP mode is excited and used for sensing in the U-shaped external PQF, which can detect a small variation of the analyte RI. The maximum sensitivity of the sensor is 33600 nm/RIU, and the average sensitivity is 21643.75 nm/RIU within the detection RI range of 1.420–1.436. The U-shaped PQF sensor will provide a new design idea for the RI sensor with high sensitivity.

No abstract

Purpose Cycloserine has been used in multidrug-resistant tuberculosis (MDR-TB) treatment since the 1950s. We evaluated the efficacy and safety of cycloserine and sought to clarify the role of cycloserine for treatment of simple MDR-TB, pre-extensively drug-resistant tuberculosis (pre-XDR-TB), and extensively drug-resistant tuberculosis (XDR-TB). Materials and methods A retrospective observational study was performed in Zhejiang Province, China. We enrolled 144 cycloserine-treated and 181 cycloserine-nontreated patients consecutively and determined the treatment outcome as the primary outcome. The proportion of patients with sputum culture conversion and the frequency of adverse drug reactions were also assessed. Results One-hundred (69.4%) out of 144 patients in the cycloserine group successfully completed treatment. The HR of any unfavorable treatment outcome after the introduction of cycloserine was 0.58 (95% CI: 0.38–0.86, P =0.008). Subgroup analysis showed that cycloser-ine could benefit simple MDR-TB cases reducing the risk of unfavorable treatment outcomes (HR: 0.43, 95% CI: 0.24–0.76, P =0.004), but not pre-XDR-TB (HR: 0.65, 95% CI: 0.30–1.38, P =0.263) or XDR-TB (HR: 0.73, 95% CI: 0.22–2.37, P =0.589). The culture conversion rate at the intensive phase was similar whether cycloserine was administered or not ( P =0.703). Of the 144 patients treated with cycloserine, a total of 16 (11.1%) patients experienced side effects attributed to cycloserine. Conclusion Cycloserine is an attractive agent for the treatment of MDR-TB, and its safety profile warrants its use in most MDR-TB cases. Cycloserine significantly improved the chance of a favorable outcome for patients with simple MDR-TB but not pre-XDR-TB and XDR-TB. Thus, more aggressive regimens might be required for pre-XDR-TB or XDR-TB patients.

No abstract