4%) and the validation cohort (AUC = 67.7%). Together, our study uncovered the microbiota spectrum of lung cancer patients and established the specific gut microbial signature for the potential prediction of the early-stage lung cancer.Background Between 1995 and 2010, the laparoscopic Heller myotomy (LHM) was considered in most centers the treatment of choice for esophageal achalasia. The technique evolved over time, and the initial thoracoscopic approach was abandoned in favor of LHM with the addition of a fundoplication, due to the high incidence of postoperative reflux. Recently, a new endoscopic technique has been adopted in the treatment of achalasia-peroral endoscopic myotomy (POEM), which has slowly become the preferred treatment modality in many centers. While POEM is as effective as LHM in relieving symptoms, it has been associated with a very high rate of pathological reflux, development of strictures, Barrett's esophagus, and adenocarcinoma. In addition, many patients still complain of heartburn and regurgitation even when treated with high doses of proton pump inhibitors. Methods We described 3 cases of achalasia patients with reflux symptoms refractory to medical treatment after POEM who underwent laparoscopic antireflux surgery. Results The operations were completed laparoscopically despite presence of mediastinal adhesions, probably secondary to micro-leaks during POEM. All patients had resolution of their symptoms. Conclusions This is the first report that describes patients who developed severe heartburn and regurgitation refractory to medical treatment following POEM, who eventually underwent a laparoscopic partial fundoplication with resolution of their symptoms. Our experience shows that post-POEM reflux is a serious concern, especially when refractory to medical treatment. We feel that this is a worrisome problem that will require frequent surgical interventions in the future.Exercise training is known to prolong the ventricular cardiomyocyte action potential duration (APD), increasing Ca2+ influx and contractility. The prolonged APD is caused in part by a decreased responsiveness to β-adrenergic agonists. Study aims are to elucidate the mechanisms by which exercise-training alters β-adrenergic regulation and determine the involvement of delayed rectifier potassium channels (IKr and IKs) in the response. Rats were randomly assigned to wheel-running trained (TRN) or sedentary (SED) groups. After 6-8 weeks of training, myocytes were isolated from the apex and base regions of the left ventricle, and current-voltage relationships of IKr and IKs were measured. Myocytes from SED and TRN rats exhibit lower IKr current compared to IKs, and regional difference in IKs was observed with higher current in apex compared to base myocytes. Wheel running decreased IKs at positive voltages and reduced IKs responsiveness to β-agonist. IKs channel subunit KCNQ1 content was higher in apex compared to base, and exercise training decreased KCNQ1 and KCNE1 subunit content in both regions. Exercise-training had no effect on β1-adrenergic receptor (β1-AR) content but reduced the kinase anchoring protein yotiao and β-adrenergic receptor kinase GRK2 compared to SED rats. The reduced KCNQ1, KCNE1, and yotiao provide a mechanism underlying the training induced decreased in IKs current, while down regulation of GRK2 would reduce inactivation of the β-AR, maintaining adrenergic stimulation of contractility. Collectively, these membrane protein changes in response to TRN provide a mechanism for prolonging the APD, increasing myocyte efficiency in low stress conditions, while increasing contractility.We examined whether a countdown (CD) before voluntary cycling exercise induced prospective vascular adjustment for the exercise and, if so, whether and how muscle sympathetic nerve activity (MSNA) was involved in the responses. Young men performed voluntary cycling in a semi-recumbent position (n=14) while middle cerebral artery blood flow velocity (VMCA; Doppler ultrasonography), heart rate (HR), arterial pressure (AP; finger photoplethysmography), oxygen consumption rate (VO2), oxygen saturation in the thigh muscle (StO2; near-infrared spectrometry), cardiac output (CO; Modelflow method) and total peripheral resistance (TPR) were measured (Exp1). Another group underwent the same exercise protocol but used only the right leg (n=10) while MSNA (microneurography) was measured in the peroneal nerve of the left leg (Exp2).  https://www.selleckchem.com/products/jsh-23.html  All subjects performed 8 trials with a ≥5-min rest between trials. In 4 trials randomly selected from the 8 trials, exercise onset was signaled by a 30-sec CD, whereas in the remaining 4 trials, exercise was started without CD. We found that CD first increased VMCA, HR, CO, and mean AP, then decreased TPR and increased StO2 and VO2 (Exp1; all, P less then 0.021). Furthermore, the CD-induced increase in mean AP decreased total MSNA and burst frequency (Exp2; both, P less then 0.048) through the baroreflex, with decreased TPR and increased StO2 (Exp2; both, P less then 0.001). The vasodilation and increased VO2 continued after the start of exercise. Thus, CD before starting exercise induced the muscle vasodilatory response with a concomitant reduction in MSNA through the baroreflex to accelerate aerobic energy production after the start of exercise.Acute intermittent hypoxia (AIH) triggers sympathetic long-term facilitation (sLTF), a progressive increase of sympathetic nerve activity (SNA) linked to central AT1 receptor (AT1R) activation by circulating angiotensin II (AngII). Here we investigated AIH activation of the peripheral renin-angiotensin system (RAS) and the extent to which the magnitude of RAS activation predicts the magnitude of AIH-induced sLTF. In anesthetized male Sprague-Dawley rats, plasma renin activity (PRA) increased in a linear fashion in response to 5 (P=0.0342) and 10 (P less then 0.0001) cycles of AIH, with PRA remaining at the 10th cycle level 1 h later, a period over which SNA progressively increased. On average, SNA ramping began at AIH cycle 4.6 ± 0.9 (n=12), and was similar in magnitude 1 h later whether AIH consisted of 5 or 10 cycles (n=6/group). Necessity of central AT1R in post-AIH sLTF was affirmed by intracerebroventricular (ICV) losartan (40 nmol, 2 µL, n=5), which strongly attenuated both splanchnic (P=0.0469) and renal (P=0.