Background Neuronal hyperactivity related to β-amyloid (Aβ) is considered an early warning sign of Alzheimer disease (AD). Although increasing evidence supports this opinion, the underlying mechanisms are still unknown. Methods Here, we recorded whole-cell synaptic currents and membrane potentials using patch clamping of acute hippocampal slices from human amyloid precursor protein (APP)/presenilin-1 transgenic (5XFAD) mice and their wild-type littermates. Biochemical methods, electron microscopic imaging, behavioral tests, and intraventricular drug delivery applied with osmotic pumps were used in this study. Results We confirmed hyperactivity of hippocampal CA1 pyramidal neurons in 5XFAD mice using whole-cell electrophysiological recording at 2.5 months old, when local Aβ-positive plaques had not developed and only mild cognitive dysfunction occurred. We further discovered attenuated inhibitory postsynaptic currents and unchanged excitatory postsynaptic currents in CA1 pyramidal neurons, in which the intrinsic excitability was unchanged. Moreover, the density of both γ-aminobutyric acid A (GABAA) receptor subunits, α1 and γ2, was reduced in synapses of the hippocampus in transgenic mice. Intriguingly, early intervention with the GABAA receptor agonist gaboxadol reversed the hippocampal hyperactivity and modestly ameliorated cognitive performance in 5XFAD mice under our experimental conditions. Conclusions Inhibitory postsynaptic disruption critically contributes to abnormalities in the hippocampal network and cognition in 5XFAD mice and possibly in AD. Therefore, strengthening the GABAergic system could be a promising therapy for AD in the early stages.

BackgroundIt is unclear at present whether extracorporeal membrane oxygenation (ECMO) therapy can improve intestinal mucous barrier function through increased perfusion. The present study establishes an animal model for post-traumatic acute respiratory distress syndrome (ARDS) and evaluates the effect of v-vECMO treatment on the intestinal mucosal barrier.MethodPulmonary contusion combined with ischemia-reperfusion injury was induced in 30 piglets. The animals were randomly divided into control, model, and ECMO groups. Serum I-FABP, d-lactate, and endotoxin were measured over a 24-h period. The jejunum and colon were collected post-mortem and evaluated histopathologically. The tissue was also examined using electron microscopy, and intestinal tight junction proteins (ZO-1 and occludin) were measured after 24 h of ECMO therapy. Mortality rate and cause of death were also recorded.ResultsThe serum markers evaluating the intestinal mucosal barrier deteriorated in the model group compared to the control group (p < 0.05). At 2 h, serum I-FABP, d-lactate, and endotoxin were significantly increased in the ECMO group compared to the model group (p < 0.05). At 12 h, I-FABP and d-lactate in the ECMO group dropped to model group levels. Serum d-lactate was slightly lower in the ECMO group (p > 0.05) and serum I-FABP was significantly lower than in the model group (p < 0.05) at 24 h. Similarly, serum endotoxin was slightly lower in the ECMO group than in the model group (p > 0.05) at 24 h. After 24 h of ECMO therapy, the occludin and ZO-1 protein concentrations in jejunum and colon mucosa increased moderately compared to that in the model group (p < 0.05). Morphologic structure of the jejunum and colon did not improved significantly after ECMO therapy. Finally, we observed that ECMO therapy moderately decreased mortality (25% vs. 50%).ConclusionIntestinal mucosal barrier continued to deteriorate in the model group. Although early ECMO therapy aggravates intestinal mucosal injury, the damage gradually improves later during therapy. The results show that ECMO therapy has a protective effect on the intestinal mucosal barrier in the later treatment stage.

Background: From the traditional Chinese medicine (TCM) constitution theory perspective, the phlegm-dampness constitution is thought to be closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). However, this viewpoint still lacks rigorous statistical evidence. This study aimed to test the association between the phlegm-dampness constitution and NAFLD.Methods: We conducted a cross-sectional study. Participants were residents living in Chengdu, China, undergoing health checkups at the health management center of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between December 2018 and September 2020. TCM constitution type was diagnosed by DAOSH four examinations instrument, NAFLD was diagnosed according to the liver ultrasonography and medical history. Multivariate logistic regression and propensity score matching (PSM) were used to analyze a total of 1,677 qualified data.Results: 1,037 participants had biased constitution(s), 67.8% of which had mixed constitutions (with at least two constitutions). Among 1,677 participants, the phlegm-dampness constitution was associated with the yang-deficiency, yin-deficiency, dampness-heat, qi-depression, and blood-stasis constitutions. The correlation coefficients were 0.11, 0.32, 0.42, 0.20, 0.14, respectively. Between the phlegm-dampness constitution and NAFLD, the odds ratio (OR) and the 95% confidence interval (CI) was 2.05 (1.57–2.69) in the crude model. After adjusting for age, gender, Body mass index (BMI), other biased constitutions, smoking, high blood pressure, diabetes, and dyslipidemia, the OR reduced to 1.51 (1.04–2.18). The associations of seven other biased TCM constitutions and NAFLD were not statistically significant in the fully adjusted model. The PSM analysis showed consistent results with the logistic regression.Conclusions: Among eight biased TCM constitutions, the phlegm-dampness constitution is independently associated with NAFLD. We speculate the phlegm-dampness constitution is a risk factor of NAFLD. Longitudinal studies are needed to confirm this causal relationship in the future. In addition, inconsistent with some TCM practitioners' experience, we disagree that the blood-stasis constitution is associated with NAFLD.

The electric shock has been proposed as one of the new needling sensations in recent years. In acupuncture sensation scales, the electric shock is included by ASS and SNQS, but not SASS, MASS, and C-MMASS. Some scholars argue that the electric shock is a normal needling sensation, but some researchers do not agree with this view. This problem has not been resolved due to a lack of evidence from basic research. Literature and research point out that the electric shock is caused by inserting a needle into the nerve directly. A question of considerable scientific and practical interest is whether the electric shock should be a normal needling sensation. In this article, we review the historical documentation of the needling sensation and the process of formulating and improving acupuncture sensation scales to suggest that the electric shock may not be a normal needling sensation. Secondly, we collected and analyzed cases of nerve injury caused by acupuncture accompanied by the electric shock and why acupuncture caused the electric shock without nerve injury. It suggests that there may be a correlation between the electric shock and peripheral nerve injury, and acupuncture manipulation is an essential factor in adverse acupuncture events. Finally, we put forward that the electric shock during acupuncture is a warning sign that the peripheral nerve may be injured, rather than a normal needling sensation. In the future, we hope to have experimental studies on the mechanism of the electric shock or observational studies on the correlation between the electric shock and peripheral nerve injury to verify.

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