Restoration of FMRP expression in adult V1 neurons rescues visual deficits in a mouse model of fragile X syndrome

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.

Methodological study of rapid health technology assessment of drugs ：taking antitumor drugs as an example / 中国药房

OBJECT IVE To develop a rapid health technology assessment （rHTA）methodology of drugs based on evidence integration and value judgment ，which is suitable for China ’s national conditions. METHODS The literature review was adopted to study health technology assessment （HTA）and multi-criteria decision analysis （MCDA），and then rHTA method based on China ’s condition was formulated preliminarily with anti-tumor drugs ；the method of rHTA was demonstrated by expert consultation ； finally，the feasibility of rHTA was preliminarily verified taking the drugs for the treatment of non-small cell lung cancer as an example. RESULTS Established rHTA method combined the theory and principles of HTA and MCDA ：HTA method was used to guide the collection and synthesis of literature and real-world evidence ，while MCDA made the value measurements of achievable evidences by various stakeholders from different views ；it established the working process ，evaluation dimensions ，evaluation indicators and scoring system of rHTA. The feasibility of this method was verified by the drug example of treating non-small cell lung cancer. CONCLUSIONS A set of drug-driven rHTA methodology guidance based on HTA and MCDA is established. It can quickly collect and integrate evidence ，and provide evidence support for decision makers in a short time.