In asthma, mucus hypersecretion is thought to be a prominent pathological feature associated with widespread mucus plugging. However, the current treatments for mucus hypersecretion are often ineffective or temporary. The potential therapeutic targets of mucus hypersecretion in asthma remain unknown. Here, we show that Lyn is a central effector of endoplasmic reticulum stress (ER stress) and mucous hypersecretion in asthma. In Lyn-transgenic mice (Lyn-TG) and wild-type (WT) C57BL/6J mice exposed to ovalbumin (OVA), Lyn overexpression attenuates mucus hypersecretion and ER stress. Interleukin 13 (IL-13) induced MUC5AC expression by enhancing ER stress in vitro. Lyn serves as a negative regulator of IL-13-induced ER stress and MUC5AC expression. We further find that an inhibitor of ER stress, which is likely involved in the PI3K p85α/Akt pathway and NFκB activity, blocked MUC5AC expression in Lyn-knockdown cells. Furthermore, PI3K/Akt signaling is required for IL-13-induced ER stress and MUC5AC expression in airway epithelial cells. The ER stress regulation of MUC5AC expression depends on NFκB in Lyn-knockdown airway epithelial cells. Our studies indicate not only a concept of mucus hypersecretion in asthma that involves Lyn kinase but also an important therapeutic candidate for asthma.

The aim of this study was to retrospectively evaluate the effectiveness of intravesical electrical stimulation (IVES) on detrusor underactivity (DU).From 2009 to 2016, a total of 105 patients with symptoms of DU who were treated with IVES were included in this retrospective study. The medical records, physical examination findings, urine culture results, and video-urodynamic studies were reviewed. Changes in post-void residual urine (PVR) and voiding efficiency (VE) were included for evaluation of efficacy. Patients achieving a >50% reduction in the PVR were regarded as responders. A >80% reduction in the PVR was considered obvious improvement. A questionnaire was administered to patients with bladder sensation.Of the 105 patients, the information of residual urine volume and voiding volume was obtained in 89 patients, and detailed pre- and post-IVES bladder sensation information was available on 96 patients. Of the 89 patients, 47.2% (42/89) were responders and achieved a >50% reduction in the PVR. Obvious improvement in the PVR, defined as a >80% reduction, occurred in 27% (24/89) of the patients. VE developed in 76.4% (68/89) of the patients, and 30.3% (27/89) of the patients increased >50%. Significant improvements in the PVR and VE were observed during IVES treatment (P < .05). Based on the questionnaire, bladder sensation developed and was sustained in 44.8% (43/96) of the patients.IVES provides a promising method for improving the PVR and VE in a majority of patients with DU. Thus, IVES is worth to further study and carry out.

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