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Background Depression is the most common form of mental disorder in community and health care settings and current treatments are far from satisfactory. Vagus nerve stimulation (VNS) is an FDA-approved somatic treatment for treatment-resistant depression. However, the involvement of surgery has limited VNS only to patients who have failed to respond to multiple treatment options. Transcutaneous VNS (tVNS) is a relatively new, non-invasive VNS method based on the rationale that there is afferent / efferent vagus nerve distribution on the surface of the ear. The safe and low-cost characteristics of tVNS have the potential to significantly expand the clinical application of VNS. Methods In this study, we investigated how tVNS can modulate the default mode network (DMN) functional connectivity (FC) in mild or moderate major depressive disorder (MDD) patients. Forty-nine MDD patients were recruited, and received tVNS or sham tVNS (stVNS) treatments. Result 34 patients completed the study and were included in data analysis. After one month of tVNS treatment, the 24-item Hamilton Depression Rating Scale (HAMD) score reduced significantly in the tVNS group as compared to the stVNS group. The FC between the DMN and anterior insula and parahippocampus decreased; the FC between the DMN and precuneus and orbital prefrontal cortex increased compared to stVNS. All these FC increases are also associated with HAMD reduction. Conclusions tVNS can significantly modulate the DMN FC of MDD patients; our results provide insights to elucidate the brain mechanism of tVNS treatment for MDD patients.

Background Depression presents a significant burden to both patients and society. One treatment that has emerged is vagus nerve stimulation (VNS), an FDA-approved physical treatment for depressive disorders. However, the application of this intervention has been limited by the involvement of surgery and potential side effects. The aim of this study is to explore the effectiveness of stimulating the superficial branches of the vagus nerve as a solo treatment for MDD. Methods This is a nonrandomized, controlled study. The first cohort of patients (n = 91) only received transcutaneous auricular VNS (taVNS) for 12 weeks. In the second cohort (n = 69), patients first received 4 weeks of sham taVNS followed by 8 weeks of taVNS. All treatments were self-administered by the patients at home after they received training from the hospitals. The primary outcome measurement was the 24-item Hamilton Depression Rating Scale measured at weeks 0, 4, 8, and 12. Data analysis included a timelag analysis comparing 1) real and sham taVNS groups at week 4; 2) the real taVNS group at week 4 vs the sham taVNS group at week 8 (fourth week of real taVNS following 4 weeks of sham); and 3) the real taVNS group at week 8 vs the sham taVNS group at week 12 (eighth week of real taVNS following sham). Results After four weeks of treatment, MDD patients in the taVNS group showed greater improvement than that of the sham taVNS group as indicated by both Hamilton score changes as well as response and remission rates at week four. In addition, we also found that the clinical improvements continued until week 12 during taVNS. Limitations Patients were not randomized in this study. Conclusions Our results suggest that taVNS is a promising, safe, and cost-effective therapeutic method for mild and moderate MDD.

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Auricular acupuncture has been utilized in the treatment of diseases for thousands of years. Dr. Paul Nogier firstly originated the concept of an inverted fetus map on the external ear. In the present study, the relationship between the auricular acupuncture and the vagal regulation has been reviewed. It has been shown that auricular acupuncture plays a role in vagal activity of autonomic functions of cardiovascular, respiratory, and gastrointestinal systems. Mechanism studies suggested that afferent projections from especially the auricular branch of the vagus nerve (ABVN) to the nucleus of the solitary tract (NTS) form the anatomical basis for the vagal regulation of auricular acupuncture. Therefore, we proposed the “auriculovagal afferent pathway” (AVAP): both the autonomic and the central nervous system could be modified by auricular vagal stimulation via projections from the ABVN to the NTS. Auricular acupuncture is also proposed to prevent neurodegenerative diseases via vagal regulation. There is a controversy on the specificity and the efficacy of auricular acupoints for treating diseases. More clinical RCT trials on auricular acupuncture and experimental studies on the mechanism of auricular acupuncture should be further investigated.

As the therapeutic agent for antiviral applications, the clinical use of oseltamivir is limited with the appearance of drug-resistant viruses. It is important to explore novel anti-influenza drugs. The antiviral activity of silver nanoparticles (AgNPs) has attracted increasing attention in recent years and was a possibility to be employed as a biomedical intervention. Herein, we describe the synthesis of surface decoration of AgNPs by using oseltamivir (OTV) with antiviral properties and inhibition of drug resistance. Compared to silver and oseltamivir, oseltamivir-modified AgNPs (Ag@OTV) have remarkable inhibition against H1N1 infection, and less toxicity was found for MDCK cells by controlled-potential electrolysis (CPE), MTT, and transmission electron microscopy (TEM). Furthermore, Ag@OTV inhibited the activity of neuraminidase (NA) and hemagglutinin (HA) and then prevented the attachment of the H1N1 influenza virus to host cells. The investigations of the mechanism revealed that Ag@OTV could block H1N1 from infecting MDCK cells and prevent DNA fragmentation, chromatin condensation, and the activity of caspase-3. Ag@OTV remarkably inhibited the accumulation of reactive oxygen species (ROS) by the H1N1 virus and activation of AKT and p53 phosphorylation. Silver nanoparticle based codelivery of oseltamivir inhibits the activity of the H1N1 influenza virus through ROS-mediated signaling pathways. These findings demonstrate that Ag@OTV is a novel promising efficient virucide for H1N1.

preparation of vagal nerves and spinal cord, while the inhibitory response induced by stimulating homosegmental acupoints is involved in the intact preparation of sympathetic nerves. Only the acupuncture-stimulation with intensity over the threshold of Aδ and/or C afferent fibers can markedly modulate gastrointestinal motility. INTRODUCTIONAcupuncture, a commonly used neuromodulating technique, has been widely accepted in the treatment of pain syndromes [1] . It modulates the functions of visceral organs by inducing activation of the somato-visceral reflexes and change of the autonomic nervous system [2][3][4] . Electro-acupuncture therapy is increasingly adopted in Western countries. Acupuncture involves stimulating specific somatic points on the body by puncturing the skin with a needle. Heat, pressure or impulses of electrical energy can also stimulate the points. It was reported that the nervous system, neurotransmitters and endogenous substances respond to electro-acupuncture. Abundant information is now available concerning the neurobiological mechanisms of acupuncture related with the neural pathways and neurotransmitters/hormonal factors that mediate autonomic regulation, pain relief and other therapeutics [5] . Being a kind of traditional technique with a long history, acupuncture has been used to treat a variety of diseases including pain. Electrophysiological studies showed that acupuncture might inhibit the neuron discharge induced by pain of both somatic and visceral sources at different levels of the central nervous system, which gives a good explanation for the clinic phenomena in which acupuncture produces quick effect on somatic and visceral pain and relatively slow and long post-effect. Though there are data relating the modulation of somatic afferent inputs on visceral nociception or dysfunction, evidence for the role of acupuncture in this process is not sufficient. Abstract AIM: To investigate the acupuncture-modulated gastric motility and its underlying neural mechanism. BASIC RESEARCH METHODS:Intragastric pressure and/or waves of gastric contraction in rats were recorded by intrapyloric balloon and changes of gastric motility induced by acupuncture stimulation were compared with the background activity before any stimulation. Gastrovagal or splanchnic-sympathetic nerves were recorded or cut respectively for investigating the involvement of autonomic nerve pathways. Spinalization experiment was also performed. RESULTS:Acupuncture-stimulation by exciting Aδ and/ or C afferent fibers, could only modulate gastric motility. Acupuncture-stimulation on fore-and hind-limbs evoked a moderate gastric motility followed by increased vagus discharges with unchanged sympathetic activity, while the same stimulus to the acupoints in abdomen resulted in reversed effects on gastric motility and autonomic nervous activities. The inhibitory gastric response was completely abolished by splanchnic denervation, but the facilitative gastric response to stimulation of acupoints in limbs was not influenced, which ...

The cyclic nucleotide phosphodiesterase10A (PDE10) has been mostly studied as a therapeutic target for certain psychiatric and neurological conditions, although a potential role in tumorigenesis has not been reported. Here we show that PDE10 is elevated in human colon tumor cell lines compared with normal colonocytes, as well as in colon tumors from human clinical specimens and intestinal tumors from ApcMin/+ mice compared with normal intestinal mucosa, respectively. An isozyme and tumor-selective role of PDE10 was evident by the ability of small molecule inhibitors and siRNA knockdown to suppress colon tumor cell growth with reduced sensitivity of normal colonocytes. Stable knockdown of PDE10 by shRNA also inhibits colony formation and increases doubling time of colon tumor cells. PDE10 inhibition selectively activates cGMP/PKG signaling to suppress β-catenin levels and T-cell factor (TCF) transcriptional activity in colon tumor cells. Conversely, ectopic expression of PDE10 in normal and precancerous colonocytes increases proliferation and activates TCF transcriptional activity. These observations suggest a novel role of PDE10 in colon tumorigenesis and that inhibitors may be useful for the treatment or prevention of colorectal cancer.