Cardiomyocyte death is one major factor in the development of heart dysfunction, thus, understanding its mechanism may help with the prevention and treatment of this disease. Previously, we reported that anti-β1-adrenergic receptor autoantibodies (β1-AABs) decreased myocardial autophagy, but the role of these in cardiac function and cardiomyocyte death is unclear. We report that rapamycin, an mTOR inhibitor, restored cardiac function in a passively β1-AAB-immunized rat model with decreased cardiac function and myocardial autophagic flux. Next, after upregulating or inhibiting autophagy with Beclin-1 overexpression/rapamycin or RNA interference (RNAi)-mediated expression of Beclin-1/3-methyladenine, β1-AAB-induced autophagy was an initial protective stress response before apoptosis. Then, decreased autophagy contributed to cardiomyocyte death followed by decreases in cardiac function. In conclusion, proper regulation of autophagy may be important for treating patients with β1-AAB-positive heart dysfunction.
We report on the experimental demonstration of stable all-optical switching between two steady state values of optical bistability from a laser diode end-pumped quasi-three-level Tm,Ho:LLF laser in the 2 µm spectral region. The width of the hysteresis cycle and jump power values can be efficiently controlled by changing the length of the cavity, which is very important to adjust and optimize the optical switching process. The all-optical bistable switching effect is realized by only adding short positive and negative trigger pulses to the pump light. This is, to our knowledge, the first observation of all-optical bistable switching in a rare earth doped solid state laser.
Disordered motility is one of the most important pathogenic characteristics of unctional dyspepsia (FD), although the underlying mechanisms remain unclear. Since the sympathetic system is important to the regulation of gastrointestinal motility, the present study aimed to investigate the role of norepinephrine (NE) and adrenoceptors in disordered gastric motility in a rat model with FD. The effect of exogenous NE on gastric motility in control and FD rats was measured through an organ bath study. The expression and distribution of β-adrenoceptors were examined by real-time PCR, Western blotting and immunofluorescence. The results showed that endogenous gastric NE was elevated in FD rats, and hyperreactivity of gastric smooth muscle to NE and delayed gastric emptying were observed in the rat model of FD. The mRNA levels of β1-adrenoceptor and norepinephrine transporter (NET) and the protein levels of β2-adrenoceptor and NET were increased significantly in the gastric corpus of FD rats. All three subtypes of β-adrenoceptors were abundantly distributed in the gastric corpus of rats. In conclusion, the enhanced NE and β-adrenoceptors and NETs may be contributed to the disordered gastric motility in FD rats.
Esophageal achalasia is a type of motility disorder characterized by incomplete relaxation of lower esophageal sphincter (LES) and absence of esophageal peristalsis. Peroral endoscopic myotomy (POEM) is a new treatment option for achalasia that is less invasive, more effective, and safe as compared to surgery. High-frequency electrotome is commonly used in POEM, but takes longer time to make the tunnel in the esophagus and causes many complications. The thulium laser decreases the risk of bleeding and perforation in endoscopy but has not been reported in digestive diseases, especially in POEM. Therefore, the aim of this study is to evaluate the feasibility of the 1940 nm thulium laser in POEM. From March 2015 to August 2015, five patients with achalasia at the Digestive department, Beijing Friendship Hospital, Capital Medical University, Beijing, China were included. Before the procedure, the patients' gender, age, and duration of symptoms were recorded. Eckardt symptom score and LES thickness, which measured by endoscopic ultrasonography, were recorded. While the subtypes of achalasia (according to the Chicago classification), lower esophagus sphincter resting pressure (LESRP) and integrated relaxation pressure (IRP) were measured by HRM for all patients. Barium esophagram was also used to rule out anatomical lesions, esophageal varices, or neoplasia, which may cause similar symptoms. All examinations were performed one week before POEM. POEM was performed with the 1940 nm thulium laser under general anesthesia. Eckardt score, procedure duration, myotomy length, and complications were recorded one week after POEM. All the patients were followed-up at two weeks and four weeks after POEM. POEM was successfully performed in all five patients. The mean age of the patients was 38.8 years (24-54 years). Achalasia subtypes were type I (n = 1), II (n = 2), and III (n = 2). The operation duration was 186, 180, 111, 75, and 126 minutes for the five cases. Pre/postprocedure Eckardt scores were 3/0, 7/0, 5/1, 6/0, and 9/0. Pre/postprocedure LESRP (mmHg) were 45.3/26.4, 18.0/1.1, 25.8/10.4, 16.5/11.2, and 24.2/20.8. Pre/postprocedure IRP (mmHg) were 27.3/15.5, 15.4/4.2, 5.7/6.8, 15.5/10.1, and 13.1/14, respectively. No adverse events occurred during the procedure. After POEM, subcutaneous emphysema occurred in case 1 on the first day, which relieved spontaneously after two days without special intervention. Infection occurred in case 5 on the day of POEM was healed with antibiotics three days later. The 1940 nm thulium laser is feasible for POEM procedure. Further studies are needed to determine whether the 1940 nm thulium laser is better than high-frequency electrotome.
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