Identification of a psychiatric risk gene NISCH at 3p21.1 GWAS locus mediating dendritic spine morphogenesis and cognitive function.

BACKGROUND: Schizophrenia and bipolar disorder (BD) are believed to share clinical symptoms, genetic risk, etiological factors, and pathogenic mechanisms. We previously reported that single nucleotide polymorphisms spanning chromosome 3p21.1 showed significant associations with both schizophrenia and BD, and a risk SNP rs2251219 was in linkage disequilibrium with a human specific Alu polymorphism rs71052682, which showed enhancer effects on transcriptional activities using luciferase reporter assays in U251 and U87MG cells. METHODS: CRISPR/Cas9-directed genome editing, real-time quantitative PCR, and public Hi-C data were utilized to investigate the correlation between the Alu polymorphism rs71052682 and NISCH. Primary neuronal culture, immunofluorescence staining, co-immunoprecipitation, lentiviral vector production, intracranial stereotaxic injection, behavioral assessment, and drug treatment were used to examine the physiological impacts of Nischarin (encoded by NISCH). RESULTS: Deleting the Alu sequence in U251 and U87MG cells reduced mRNA expression of NISCH, the gene locates 180 kb from rs71052682, and Hi-C data in brain tissues confirmed the extensive chromatin contacts. These data suggested that the genetic risk of schizophrenia and BD predicted elevated NISCH expression, which was also consistent with the observed higher NISCH mRNA levels in the brain tissues from psychiatric patients compared with controls. We then found that overexpression of NISCH resulted in a significantly decreased density of mushroom dendritic spines with a simultaneously increased density of thin dendritic spines in primary cultured neurons. Intriguingly, elevated expression of this gene in mice also led to impaired spatial working memory in the Y-maze. Given that Nischarin is the target of anti-hypertensive agents clonidine and tizanidine, which have shown therapeutic effects in patients with schizophrenia and patients with BD in preliminary clinical trials, we demonstrated that treatment with those antihypertensive drugs could reduce NISCH mRNA expression and rescue the impaired working memory in mice. CONCLUSIONS: We identify a psychiatric risk gene NISCH at 3p21.1 GWAS locus influencing dendritic spine morphogenesis and cognitive function, and Nischarin may have potentials for future therapeutic development.

Approach to the road of vigorously developing Chinese medicine by scientific location of channels and collaterals / 中国针灸

Through researches of channels and collaterals and clinical practice of many years, the authors understand that Chinese medicine, which considers the human body as an interrelated, mutual constraints, whole, dynamic living system, has gradually become an important part of modern medicine. Channels and collaterals are a closed loop system which is communicated and linked by energy and information in the form of electromagnetic oscillation, reflecting many characteristics similar to quantum. Channels and collaterals are not a fixed organizational structure. Studies on channel and collaterals find that the track of the propagated sensation along channels (PSC) have the phenomenon drifting about. This exactly reflects the law of channels dynamically running. By information triggering and living resonance, channels and collaterals bring into play entirely regulative action. The innovative treatment of channels and collaterals followed by characteristics and laws of quantum can get a better curative effect. Theory of channels in the position of quantum information medical science provides an important breach for modernization of Chinese medicine.

Meridian regulation is a course of communicating and implicating of the informational system with the material system / 中国针灸

<p><b>OBJECTIVE</b>To approach to the intrinsic mechanism of meridian regulation.</p><p><b>METHODS</b>Summarize and analyze the results of the author's studies and the development of other studies about life regulating and meridian at home and abroad.</p><p><b>CONCLUSION</b>The regulating mechanism of meridians has two levels. The macroscopic regulation center is the brain, and the microscopic regulation base is the energy and informational current that depends on electromagnetic and chemical oscillation mainly. The meridian regulation is the process of the energy and informational system communicating and implicating with the material system. Neuroendocrine is the link of communicating and implicating, and Ca2+ oscillation frequencies exert intermediary function between the two systems.</p>

Relationship of meridians with human material and energy systems study on theory and clinical application of meridians (IV) / 中国针灸

<p><b>OBJECTIVE</b>To expound the relationship between meridians and the human two information systems, material system and energy system.</p><p><b>METHODS</b>Summarize and analyze the results of experimental and other studies.</p><p><b>CONCLUSION</b>The carrier of the meridian is human material system. The nerve, body fluid, microcirculation and chemical factors take part in meridian circulation, and it must depend on the energy information system which works mainly at the form of electromagnetic and chemical oscillation with functions of physiological regulation and pathological repair. Oscillation parameters include various signals of regulating development and physiologic activities, and coordinate functions of organs and tissues. The meridians have the "quantum" characteristics, material particles coexist and exchange each other with electromagnetic and chemical oscillation characteristic.</p>

Study on theory and clinical application of meridians (III) / 中国针灸

<p><b>OBJECTIVE</b>To probe into essence of meridians.</p><p><b>METHODS</b>To examine meridians, acupoints, brain and relative organs by SQUID and fMRI, and to analyze the results.</p><p><b>CONCLUSION</b>A relative stable circular current of electromagnetic and chemical oscillation along the low electric resistance pathway was found. Competition of different frequency oscillation often yield resonance in some positions of the human body so as to form "oscillatory network" and "strange point" with the electromagnetic and chemical oscillation circulating dominant position in the body, which is possibly meridians and acupoints with regulative actions. The brain is the center of meridians. In different physiological or pathological process, characteristic changes and negatively correlative phenomenon of electromagnetic spectrum at acupoints and the brain are possibly key mechanisms in dynamic regulation of meridians.</p>