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Yu Chen,1 Ruohuang Lu,2 Yang Wang,3 Pingping Gan1 1Department of Oncology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Stomatology, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Pingping Gan, Department of Oncology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86 13874975101, Email gppxy@csu.edu.cnPurpose: Paclitaxel-induced peripheral neuropathy (PIPN) is increasingly becoming one of the most widespread adverse effects in the treatment of cancer patients, and further precipitate neuroinflammation in the nervous system. Interestingly, Shaoyao Gancao Decoction (SGD), a traditional Chinese analgesic prescription, has emerged as a primary adjuvant to chemotherapy in relieving side effects, especially in the case of PIPN. However, the underlying mechanism of SGD functioning in PIPN remains elusive. Accordingly, the current study set out to explore the potential axis implicated in the functioning of SGD in PIPN.Methods: First, network pharmacology was adopted to predict the role of the transient receptor potential vanilloid type 1 (TRPV1) protein in treating PIPN with SGD. Subsequently, the effects of SGD treatment on mechanical allodynia and thermal hyperalgesia were evaluated in rat PIPN models. Based on the bioinformatics information and current literature, paclitaxel activates toll-like receptor 4 (TLR4) induces the sensitization of TRPV1 mechanistically. Thereafter, TLR4-myeloid-differentiation response gene 88 (MyD88) signaling and TRPV1 expression patterns in dorsal root ganglias (DRGs) were measured by means of Western blotting, qPCR and immunofluorescence.Results: Initial bioinformatics reared a total of 105 bioactive compounds and 1075 target genes from SGD. In addition, 40 target genes intersected with PIPN were considered as potential therapeutic genes. Based on the network analysis, SGD was found to exert its analgesic effect by reducing the expression of TRPV1. Further experimentation validated that SGD exerted an analgesic effect on thermal hyperalgesia in PIPN models, such that this protective effect was associated with the suppression of TRPV1 and TLR4-MyD88 Signaling over-expression.Conclusion: Collectively, our findings indicated that SGD ameliorates PIPN by inhibiting the over-expression of TLR4-MyD88 Signaling and TRPV1, and further highlights the use of SGD as a potential alternative treatment for PIPN.Keywords: paclitaxel-induced peripheral neuropathy, Shaoyao Gancao Decoction, transient receptor potential vanilloid type 1, network pharmacology, paclitaxel, toll-like receptor 4

The microparticle-initiated breakdown plays a key role in the failure of gas switches and has become an active area of investigation in gas discharge recently. The mechanism of the microparticle-initiated breakdown in a 2-mm air gap is studied by experiments and simulations in this article. The dynamics of the microparticle in the electric field is obtained, and four breakdown modes are acquired from the picture of the high-speed camera. The probabilities of breakdown for the 200-, 300-, and 500- $\mu \text{m}$ Cu microparticles under different voltages are presented, and the corresponding lowest breakdown voltages reduce to 65%, 56%, and 47% of the static-breakdown voltage. The relation between the breakdown voltage and position of the microparticle is calculated based on the Townsend theory. The simulated results agree well with the experimental results. The breakdown process and evolution of the plasma are also revealed with PIC simulations.

The proposed Compact Intense Fast NEutron Facility (CIFNEF) will have a wide range of applications, including the investigation of the exotic structure of neutron-rich nuclei, data for the nuclear fission , and the simulation of the neutron field in a star. To satisfy aims of producing high-intensity fast neutrons and forward neutrons with very low environmental background, the CIFNEF linac should have the capacity of accelerating continuous wave (CW) deuteron (D + ), hydrogen ( H 2 + ) and lithium (7Li 3 + ) beams to 2.5 MeV/u with maximum beam currents of 10 mA, 5 mA and 10 uA, respectively. Based on the above requirements, we proposed a novel compact linac using a combination of RFQ and DTL structures. The dynamics of RFQ and DTL are completed to meet all requirements and start-to-end simulation results show that the three ion species can be accelerated to the final energy with transmission efficiency above 99% as well as good beam quality with lower emittance growth. In addition, we performed error sensitivity analysis and combined error study to evaluate the error tolerance limits of the obtained design.

The present study proposes a new approach for direct CO

For a high-current Radio Frequency Quadrupole (RFQ) accelerator, space charge will strongly affect the stability of beams, which brings challenges and difficulties to the beam dynamics design. For an in-depth study of this space charge effect, a project has been proposed by Peking University and the Institute of Modern Physics of the Chinese Academy of Sciences. This project requires a 162.5 MHz RFQ to accelerate a 100-mA continuous-wave (CW) proton beam to 3 MeV. The beam dynamics design of this RFQ is based on the four-section procedure with improved radial focusing strength along the RFQ. We have investigated the relationship between limiting current and beam transmission to analyze the reasons for emittance growth and beam loss. We have also carried out an irradiation experiment based on this beam dynamics design to study the irradiation damage of the electrode surface, as this can be one main reason for reduced transmission or unstable operation that most existing high-current RFQs encounter after long-time operation. The results show that low-energy beam losses need to be kept as low as possible to prolong the life of the RFQ electrodes. The final simulated transmission efficiency reached 99.8%, as confirmed by the code toutatis .

Free radical-induced oxidative damage occurs rapidly and is of primary importance during the secondary pathophysiological cascades of traumatic brain injury (TBI). Hydroxysafflor yellow A (HSYA) is a constituent of the flower petals of Carthamus tinctorius (safflower) and may represent a potential therapeutic strategy to improve outcomes following TBI. The present study aimed to identify HSYA in the brain tissues of rats exposed to TBI to determine its absorption and to investigate the underlying effects of HSYA on antioxidant enzymes in the brain tissues of TBI rats. To determine the absorption of HSYA for the investigation of the underlying antioxidant effects of HSYA in TBI, the presence of HSYA in the brain tissues of the TBI rats was identified using an ultra performance liquid chromatography‑tandem mass spectrometry method. Subsequently, the state of oxidative stress in the TBI rat model following the administration of HSYA was investigated by determining the levels of antioxidant enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT), and the ratio of glutathione (GSH)/glutathione disulfide (GSSG). The data obtained demonstrated that HSYA was absorbed in the brain tissues of the TBI rats. HSYA increased the activities of SOD and CAT, the level of GSH and the GSH/GSSG ratio. However, HSYA concomitantly decreased the levels of MDA and GSSG. These preliminary data suggest that HSYA has the potential to be utilized as a neuroprotective drug in cases of TBI.

Ethnopharmacological relevance Zhiqiao–Houpu herb-pair (ZQHPHP), composed of Fructus Aurantii (Zhiqiao [ZQ] in Chinese) and Magnolia officinalis (Houpu [HP] in Chinese), is a traditional herbal formula that has been extensively used for treating gastrointestinal motor dysfunction. The aim of the study was to evaluate the effect and possible mechanism of ZQHPHP on gastric emptying (GE) and gastric antral smooth muscle contractility (GASMC). Materials and methods This study includes four parts: (a) study of ZQHPHP's effect on GE; (b) study of ZQHPHP's effect on gastric antral smooth muscle contractility (GASMC); (c) comparing the effects of ZQHPHP, ZQ and HP on GASMC; (d) study of antagonists or agonists on ZQHPHP-induced GASMC. A test meal of Evans blue was adopted to estimate GE in rats. A polygraph was used to measure GASMC in rats. Results The in vivo experiments demonstrated that, at the doses of 10 mg/kg bw and 20 mg/kg bw, ZQHPHP could promote GE. While, at the higher dose of 30 mg/kg bw, ZQHPHP delayed the GE. From the in vitro experiments we found that ZQHPHP (3–10 μg/ml) concentration-dependently increased the mean amplitude of contractions in the antral circular strip compared to untreated controls. While, in the concentration of 30 μg/ml, ZQHPHP prohibited GASMC. Besides, atropine blocked the stimulatory effect of ZQHPHP on GASMC and norepinephrine partly prohibited the stimulatory effect of ZQHPHP on GASMC, whereas isoproterenol showed no effect. From the in vitro experiment, we also found that ZQ and HP used together can synergistically increase gut motor. Conclusions The experiment indicated that ZQHPHP could induce bidirectional regulation on gastric motility. ZQ and HP used together can synergistically increase gut motor at a certain dosage. Lower dosage of ZQHPHP increases gastric motility, while higher dosage produces inhibition. In addition, the improvement of gastric motility by ZQHPHP is predominantly involved with muscarinic receptors and secondarily with alpha-receptors.

A simple, novel, specific, rapid and reproducible ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry method has been developed and validated for the determination of hydroxysafflor yellow A (HSYA) in biological fluids (plasma, urine and cerebrospinal fluid) of patients with traumatic brain injury after intravenous injection of Xuebijing (XBJ). Liquid-liquid extraction was performed, and separation was carried out on an Acquity UPLC™ BEH C18 column, with gradient elution using a mobile phase composed of methanol and 0.1% formic acid at a flow rate of 0.3 mL/min. A triple quadrupole tandem mass spectrometer with electrospray ionization was used for the detection of HSYA. The mass transition followed was m/z 611.0 → 491. The retention time was less than 3.0 min. The calibration curve was linear in the concentration range from 2 to 6125 ng/mL for cerebrospinal fluid, plasma and urine. The intra- and inter-day precisions were