Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors/antagonists & inhibitors* ; G2 Phase Cell Cycle Checkpoints ; Histone Deacetylase Inhibitors/pharmacology* ; Histone Deacetylases/metabolism* ; M Cells ; Multiple Myeloma/drug therapy*

Compound Traditional Chinese Medicine (CTCM) applying for FDA approval as botanical drug is a systemic and innovative work.Compound Danshen Dripping Pill (T89) is the first CTCM completed FDA global multi-center Phase Ⅲ clinical trial,which has become a benchmark for TCM globalization.Extensive experiences have been accumulated through the 20 years' research and development.Tasly fully considered the characteristics of CTCM while complying with FDA regulations during the entire application process.In which,product indication was clearly defined and agreed,clinical trial protocol was scientifically and innovatively designed with gold standard,phase Ⅱ study was well completed,SPA for phase Ⅲ study was obtained,and eventually the global multi-center phase Ⅲ study was successfully completed.In order to better support T89's application,Tasly conducted series of additional studies and introduced many innovations,such as drug-drug interaction study for TCM,finger printing study for CTCM,quality consistency study,biological assay study and etc.Globalization of T89 is not only a product creating history,but also a process for Tasly and the US FDA working together to continuously innovate and create history in innovating modern TCM standards,improving industrial chain GMP system for botanical drugs,making technical breakthroughs,exploring regulatory pathways and increasing product value.It represents the national power and historical progress in medicine.

Objective To establish a coupled model combining the rat brain nuclei microelectrode recordings and the behavioristics for rehabilitation experiment. Methods The modified indwelling tube connection fixed device was put inside the rats' back, and the microprobes were implanted into related neural nucleus. A signal connection was made between self-administration system and electrophysiological data acquisition system. The rat was addicted after training by self-administration system. The related cerebral nucleus electrophysiological sig-nals were recorded in different states of addiction. Results and Conclusion The modified indwelling tube connection fixed device has a bet-ter quality for reducing the phenomenon of leak. The signal was well in the combination of two different systems. The signals for the rat's ac-tion and neural electrical were recorded in the same time.

To investigate the relationship of the rotation stimulation with motion sickness, the expression of Fos protein in the whole brain of the rat stimulated by complex double rotation on two axes was observed in the present study. The rats were randomly divided into four groups: normal contral group; double-axes rotation stimulation group; the bilateral labyrinthectomy group; group of two-axes rotation stimulation after the bilateral labyrinthectomy. Immunohistochemical staining method was used to detect the expression of Fos protein in different regions of whole brain of the rat. The present results showed that: (1) No Fos-like immunoreactivity was detected in the brain of the rats in control group and the bilateral labyrinthectomy group; (2) In the double-axes rotation stimulation group, the Fos-like immunoreactive neurons were observed in many regions of the brain and brainstem of the rats following complex double-axes rotation stimulation, and the Fos-immunoreactivities were expressed in the nucleus. These Fos-immunopositive neurons were intensively distributed in different subnuclei of the vestibular nucleus complex (including medial, superior and spinal nuclei), nucleus of the solitary tract, locus coeruleus, medial and lateral parabrachial nucleus of the brainstem, paraventricular nucleus of the diencephalons and the amygdala of the limbic system; (3) The expression of Fos protein can be scarcely detected around forementioned regions in brains of the rats following complex two-axes rotation stimulation after the bilateral labyrinthectomy. The present results suggest that the double-axes rotation stimulation can activate effectively the vestibular neurons and many neurons of other region of the brain and brainstem are further activated through direct or indirect connections with vestibular nuclei after complex double rotation stimulation. These activated neurons may be related to the complex mechanism of the motion sickness.