Sulfur dioxide in the caudal ventrolateral medulla reduces blood pressure and heart rate in rats via the glutamate receptor and NOS/cGMP signal pathways / 生理学报

This study was designed to investigate the cardiovascular effects of sulfur dioxide (SO2) in the caudal ventrolateral medulla (CVLM) of anesthetized rats and its mechanism. Different doses of SO2 (2, 20, 200 pmol) or artificial cerebrospinal fluid (aCSF) were injected into the CVLM unilaterally or bilaterally, and the effects of SO2 on blood pressure and heart rate of rats were observed. In order to explore the possible mechanisms of SO2 in the CVLM, different signal pathway blockers were injected into the CVLM before the treatment with SO2 (20 pmol). The results showed that unilateral or bilateral microinjection of SO2 reduced blood pressure and heart rate in a dose-dependent manner (P < 0.01). Moreover, compared with unilateral injection of SO2 (2 pmol), bilateral injection of 2 pmol SO2 produced a greater reduction in blood pressure. Local pre-injection of the glutamate receptor blocker kynurenic acid (Kyn, 5 nmol) or soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 pmol) into the CVLM attenuated the inhibitory effects of SO2 on both blood pressure and heart rate. However, local pre-injection of nitric oxide synthase (NOS) inhibitor NG-Nitro-L-arginine methyl ester (L-NAME, 10 nmol) only attenuated the inhibitory effect of SO2 on heart rate but not blood pressure. In conclusion, SO2 in rat CVLM has cardiovascular inhibitory effects, and its mechanism is related to the glutamate receptor and NOS/cGMP signal pathways.

Sex Differences in Neuropathology and Cognitive Behavior in APP/PS1/tau Triple-Transgenic Mouse Model of Alzheimer's Disease / 神经科学通报·英文版

Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PS1/tau triple-transgenic AD mice (3×Tg-AD mice) and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofibrillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expression levels of hippocampal protein kinase A-cAMP response element-binding protein (PKA-CREB) and p38-mitogen-activated protein kinases (MAPK) also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB-MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.

Amyloid β protein injection into medial septum impairs hippocampal long-term potentiation and cognitive behaviors in rats / 生理学报

The specific loss of cholinergic neurons and the progressive deficits of cognitive function are the most primary characteristics of Alzheimer's disease (AD). Although the neurotoxicity of amyloid β protein (Aβ) in AD has been investigated extensively, it is still unclear whether the Aβ aggregated in the medial septum (MS), a major cholinergic nucleus projecting to the hippocampus, could affect hippocampal synaptic plasticity and further impair the memory behaviors. The present study investigated the effects of Aβ injection into the MS on hippocampal long-term potentiation (LTP) and cognitive behaviors of rats by using Morris water maze (MWM), Y maze and in vivo hippocampal LTP recording. The effects of kainic acid (KA), an agent with specific neurotoxicity to GABAergic neurons, were also observed. The results showed that: (1) Intra-MS injection of Aβ, not KA, impaired spatial learning and memory of rats in classical and reversal MWM tests; (2) Both Aβ and KA impaired novelty-seeking behavior of rats in Y maze; (3) Intra-MS injection of Aβ, not KA, suppressed in vivo hippocampal LTP in the CA1 region of rats; (4) Both Aβ and KA did not affect the motor ability in behavioral tests and the hippocampal paired-pulse facilitation (PPF) in electrophysiological recording. These results indicate that intra-MS injection of Aβ could impair spatial memory, cognitive flexibility and exploratory motivation, as well as hippocampal LTP in rats, suggesting that the cholinergic neurons in the MS and the septo-hippocampal projection could be important targets of neurotoxic Aβ, and the specific damage of cholinergic neurons in the MS is likely responsible for the impairments of hippocampal synaptic plasticity and cognitive function in AD.

Treatment of Mild-to-moderate Bronchial Asthma (Heat Wheezing Syndrome) Patients at Acute Onset with Western Medicine Combined Danlong Oral Liquid: a Multi-center, Randomized Double- blinded, Positive-controlled Clinical Trial / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the efficacy and safety of Danlong Oral Liquid (DOL) combined Western medicine (WM) in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset.</p><p><b>METHODS</b>Totally 480 mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset were randomly assigned to two groups in the ratio 3:1, the treatment group (360 cases) and the control group (120 cases). All patients received basic WM treatment. Patients in the treatment group took DOL, 10 mL each time, 3 times per day for 7 days in total, while those in the control group took Kechuanning Oral Liquid (KOL) , 10 mL each time, 3 times per day for 7 days in total. Efficacy for asthma symptoms, lung functions and scores of TCM syndrome and/or main symptoms were evaluated.</p><p><b>RESULTS</b>The percentage of clinical control and significant effectiveness of asthma symptoms in the treatment group was significantly higher than that of the control group (77.36% vs 56.07%, P < 0.01). The percentage of clinical control and significant effectiveness of lung functions in the treatment group was significantly higher than that of the control group (74.28% vs 50.00%, P < 0.01). The anterior-posterior difference in scores of TCM syndrome was significantly superior in the treatment group than in the control group (-11.26 ± 4.70 vs -9.21 ± 5.09, P < 0.01). The anterior-posterior difference in scores of main symptoms was significantly better in the treatment group than in the control group (-6.58 ± 3.08 vs -5.16 ± 3.45, P < 0.01). The incidence of adverse reactions was significantly lower in the treatment group than in the control group [1.73% (6/346 cases) vs 10.17% (12/118 cases) , P < 0.05].</p><p><b>CONCLUSION</b>DOL combined WM was superior to KOL in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset.</p>

Extracorporeal cardiac shock wave therapy for treatment of coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility and efficiency of extracorporeal cardiac shock wave therapy (CSWT) for treatment of coronary artery disease.</p><p><b>METHODS</b>Twenty-five patients with 1 - 16 years history of chronic angina pectoris underwent the CSWT. Before and after the treatment, low-dose Dobutamine stress echocardiography and (99)Tc(m)-MIBI myocardial perfusion SPECT were applied to locate the ischemic segments, detect the viable myocardium and evaluate the effect of CSWT. Under the guidance of echocardiography, CSWT was applied in R-wave-triggered manner with low energy (0.09 mJ/mm(2)) at 200 shoots/spot for 9 spots (-1-0-+1 combination). Patients were divided group A and group B. Sixteen patients in group A were applied 9 sessions on 29 segments within 3 month and nine patients in group B were applied 9 sessions on 13 segments within 1 month. Ten chronic angina pectoris patients receiving standard medication served as controls.</p><p><b>RESULTS</b>All patients completed the 9 sessions without procedural complications or adverse effects. CSWT significantly improved symptoms as evaluated by NYHA, Canadian Cardiovascular Society (CCS) class sores, Seattle angina questionnaire (SAQ), 6-min walk and the use of nitroglycerin (P < 0.05). CSWT also improved myocardial perfusion and regional myocardium function as evaluated by rest SPECT and stress peak systolic strain rate (PSSR) (P < 0.01). Myocardial perfusion improvement was more significant in group A compared with group B (1.21 ± 0.86 vs. 0.83 ± 0.80, P < 0.01). All parameters remained unchanged in control group during follow up.</p><p><b>CONCLUSION</b>These preliminary results indicate that CSWT is safe and effective on ameliorating anginal symptoms for chronic angina pectoris patients.</p>