Chronic cough due to non-acid reflux may be related to cough reflex hypersensitivity caused by neurogenic airway inflammation and mast cell activation, in which weakly acidic reflux is possibly a major factor.

-Mechanisms underlining oxidative stress-induced injury to cardiomyocytes during myocardial infarction (MI) or acute ischemia/reperfusion (I/R) are not well recognized. Forkhead box O (FOXO) transcription factors have been defined as critical mediators of oxidative stress resistance in multiple cell types, but their cardioprotective functions have not been reported previously. In the present study, we investigated the promotion to FOXO1 by the treatment with hydrogen peroxide (H 2 O 2 ) during the H 2 O 2 -induced apoptosis in cardiomyocyte H9c2 cells. We then silenced FOXO1 with FOXO1-specific siRNA, and re-evaluated the H 2 O 2 -induced apoptosis. In addition, we also examined the H 2 O 2 -induced autophagy and the autophagy induction post FOXO1 silence. Results demonstrated that H 2 O 2 induced a significantly high level of apoptosis in H9c2 cells. Interestingly, the FOXO1 in both mRNA and protein levels were not significantly regulated, however, the phosphorylated form of FOXO1 was significantly promoted in the H 2 O 2 -treated H9c2 cells. On the other hand, post the significant knockout of FOXO1 with the transfection with FOXO1-specific siRNA, the apoptosis induction was more significant in H9c2 cells subjected to H 2 O 2 . In addition, we found a significantly higher level of autophagy induction in the H 2 O 2 -treated H9c2 cells. However, the autophagy was markedly reduced by the knockout of FOXO1. In summary, these data support the critical role for FOXO1 in promoting cardiomyocytes against oxidative stress probably through inducing autophagy.

MiR-873/CDK3 has been shown to play a critical role in ERα signaling and tamoxifen resistance. Thus, targeting this pathway may be a potential therapeutic approach for the treatment of ER positive breast cancer especially tamoxifen resistant subtype. Here we report that Norcantharidin (NCTD), currently used clinically as an ani-cancer drug in China, regulates miR-873/CDK3 axis in breast cancer cells. NCTD decreases the transcriptional activity of ERα but not ERβ through the modulation of miR-873/CDK3 axis. We also found that NCTD inhibits cell proliferation and tumor growth and miR-873/CDK3 axis mediates cell proliferation suppression of NCTD. More important, we found that NCTD sensitizes resistant cells to tamoxifen. NCTD inhibits tamoxifen induced the transcriptional activity as well ERα downstream gene expressions in tamoxifen resistant breast cancer cells. In addition, we found that NCTD restores tamoxifen induced recruitments of ERα co-repressors N-CoR and SMRT. Knockdown of miR-873 and overexpression of CDK3 diminish the effect of NCTD on tamoxifen resistance. Our data shows that NCTD regulates ERα signaling and tamoxifen resistance by targeting miR-873/CDK3 axis in breast cancer cells. This study may provide an alternative therapy strategy for tamoxifen resistant breast cancer.

Modified three-step empirical therapy was as efficacious as primary three-step therapy for chronic cough, but was preferable because it had fewer side-effects.

TB-IGRA had a high sensitivity and specificity for TB infection; it could be comparable with the QFT-GIT assay. It might be a powerful assisting tool for TB infection diagnosis in the Chinese clinical setting.

Abstract.A 74-year-old female patient was admitted to hospital following a road accident with pains in the chest, abdomen, waist, back, nose, left wrist and lower limbs. After 1 week, the patient presented with gastrointestinal bleeding, and thus was treated with protein pump inhibitors (PPIs), including lansoprazole, esomeprazole and omeprazole enteric-coated tablets, in order to inhibit acid secretion and attenuate bleeding. However, the patient developed skin rashes on the chest and right lower limb and foot 28 days following treatment initiation. The skin rashes spread and ulcerated after 3 days, and were associated with tracheal mucosal injury and hemoptysis. Subsequently, treatment of the patient with PPIs was terminated, after which the tracheal hemoptysis and skin rashes markedly improved. In addition, no new skin rashes appeared following termination of the PPI treatment. In the present case, long-term treatment of an elderly patient with PPIs may have induced exfoliative dermatitis, due to hepatic ischemia, hypoxia and acute renal failure, which may have decreased the metabolism of PPIs, resulting in the accumulation of PPI metabolites. IntroductionExfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder which results in generalized eruption of the skin. It is usually caused by a variety of underlying dermatoses, drug reactions and malignancies, including lymphoma, leukemia and solid tumors (1-8). Previous studies have demonstrated that therapeutic agents including sulfonamides, captopril, phenobarbital, all-transretinoic acid and anti-tubercular drugs, such as rifampicin, isoniazid, ethambutol and pyrazinamide, may induce exfoliative dermatitis (3-8).Protein pump inhibitors (PPIs) are commonly-used prescription drugs, which can inhibit gastric acid secretion by blocking the gastric H + /K + -ATPase that is necessary for the final step of this process. PPIs are widely administered for the treatment of numerous acid-associated diseases, including peptic ulcer, gastroesophageal reflux disease and Zollinger-Ellison syndrome (9,10). In addition, PPIs have an important role in eradicating infections caused by Helicobacter pylori, controlling gastrointestinal bleeding and preventing nonsteroidal anti-inflammatory drug-induced gastric mucosal injuries. Furthermore, Ramirez et al (11) suggested that the long-term use of PPIs may be considered a major risk factor in the occurence of anaphylaxis with common PPI-induced anaphylactic symptoms including skin rashes, erythema and systemic pruritus, and rare symptoms including urticaria, herpes and skin allergic edema. In severe cases, acute diffuse epidermal necrolysis and anaphylactic shock have also been reported (12). Case reportOn September 29 th 2014, a 74-year-old female patient was admitted to Hubei General Hospital (Hubei, China) following a road accident with pains in the chest, abdomen, waist, back, nose, left wrist and lower limbs. A cranial computed tomography (CT) scan did not detect any abnormalities, whereas a nasal...

Because traditional Chinese medicine (TCM) is a complex mixture of multiple components, the application of methodologies for evaluating single-component Western medicine in TCM studies may have certain limitations. Appropriate strategies that recognize the integrality of TCM and connect to TCM theories remain to be developed. Yang-Xin-Ding-Ji (YXDJ) capsule is originally from a classical TCM formula used for the treatment of arrhythmia. In this study, we used UPLC-Q-TOF-MS detection method, coupled with the metabolic research and network pharmacology analysis, to study the scientific connotation of the YXDJ capsule. A total of 33 absorbed constituents and 23 metabolites were identified or tentatively characterized in dosed plasma and urine, and the possible metabolic pathways were mainly methylation, oxidation, sulfation, glucuronidation, and deglucosylation. We optimized the conventional process ways of network pharmacology by collecting targets based on absorbed constituents into the blood. The constituents-target disease and Kyoto Encyclopedia of Genes pathway analysis revealed that 24 absorbed constituents, 32 target genes, and 10 key pathways were probably related to the efficacy of the YXDJ capsule against arrhythmia. The results provided a scientific basis for understanding the bioactive compounds and the pharmacological mechanism of the YXDJ capsule.

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