Qihuang needle therapy in senile cervical spondylotic radiculopathy.

Background: Neurogenic cervical spondylosis [cervical spondylotic radiculopathy (CSR)] accounts for ~50-60% of all types of cervical spondylosis, and its incidence is the highest among all types of cervical spondylosis. Objective: The present study aimed to investigate the clinical efficacy of the Qihuang needle in the treatment of senile cervical radiculopathy. Methods: A total of 55 elderly patients with neurogenic cervical spondylosis were randomly divided into the general acupuncture group (27 cases) and the Qihuang acupuncture group (28 cases). The treatment given to these patients lasted for three sessions. The VAS scores and the Tanaka Yasuhisa Scale scores were compared before the treatment, after the first treatment, after the first session, and at the end of the session. Results: The basic data of the two groups before the treatment showed no difference. The VAS scores in the mackerel acupuncture group decreased significantly, whereas in the Tanaka Kangjiu Scale scores, the efficiency rates of the first and second courses of treatment increased significantly. Conclusion: The Qihuang needle therapy is recommended for the treatment of cervical spondylosis of the nerve root type. The said therapy is characterized by selection of fewer acupoints, a quick operation time, and no needle retention.

Propofol affects the growth and metastasis of pancreatic cancer via ADAM8.

BACKGROUND: Anesthesia is a major component of surgery and recently considered an important regulator of cell phenotypes. Here we aimed to investigate propofol, an anesthesia drug, in suppressing pancreatic cancer (PDAC), focusing on A disintegrin and metalloprotease 8, (ADAM8) as a molecular mediator. METHODS: Quantitative real-time PCR and western blot were used to assess the change of ADAM8 expression in Panc1 PDAC cells treated with 5 or 10 µg/mL propofol, using cells treated with BB-94 inhibitor as controls. ADAM8 activity was measured through quantifying fluorescence release induced by PEPDAB013 decomposition. MTT assay, scratch wound assay and Matrigel invasion assay were used to investigate the proliferation, migration and invasion of the cells. Western blot and immunohistochemical analysis were used to quantify integrin ß1, ERK1/2, MMP2 and MMP9 expression. RESULTS: Propofol and BB-94 reduced ADAM8 expression, cell proliferation and migration of Panc1 cells. Tumor growth was inhibited by propofol and BB-94, concomitant with downregulation of integrin ß1, ERK1/2, MMP2 and MMP9. ADAM8 is downregulated by propofol, leading to inhibition of pancreatic cancer proliferation and migration. CONCLUSION: Pancreatic tumor growth is also inhibited by propofol and BB-94, which is attributed to suppression of ERK/MMPs signaling.

Effect of sevoflurane treatment on microglia activation, NF-kB and MAPK activities.

Microglia activation has been implicated in neurodegenerative disease. Sevoflurane is fluorinated methyl isopropyl ether with anti-inflammatory activity. In this study, we evaluated the potential effects of sevoflurane on lipopolysaccharides (LPS)-induced microglia activation. We treated primary microglia cells with sevoflurane prior to LPS treatment and tested the microglia migration, the productions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-6 and interleukin-8. We also explored the effects of sevoflurane on NF-κB and p38 MAPK activation. Finally, we examined the effect of sevoflurane on cytokines production in rat brain. Sevoflurane significantly reduced LPS-induced microglial migration. Sevoflurane significantly decreased the production of pro-inflammatory cytokines both in vitro and in vivo. Sevoflurane attenuated activations of NF-κB and MAPK signaling pathways. Sevoflurane treatment decreased microglia activation by suppressing NF-kB and MAPK signaling pathways.

Morin Alleviates Vincristine-Induced Neuropathic Pain via Nerve protective Effect and Inhibition of NF-κB Pathway in Rats.

Vincristine is a toxic chemotherapeutic agent which often triggers neuropathic pain through inflammation. Morin isolated from figs (Ficus carica) exerts anti-inflammatory and neuroprotective activities. We investigated whether morin ameliorates vincristine-induced neuropathic pain and the underlying mechanism. Vincristine was injected i.p. for 10 days (day 1-5 and day 8-12). Morin was orally administered every other day from day 1 to 21. The pain behaviors were determined by measuring paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The axons of sciatic nerves were stained with toluidine blue to study the histological abnormality. Function deficit of sciatic nerves was evaluated by sciatic functional index and the sciatic nerve conduction velocity. Neuronal excitability was assessed electrophysiologically and inflammatory mediators were detected using western blotting in dorsal root ganglia. The vincristine-induced reduction in PWT, PWL, and body weight gain was attenuated by morin. Morin restored the sciatic nerve deficits both histologically and functionally in vincristine-injected rats. The vincristine-induced neuronal hyperexcitability and increase in the expression of IL-6, NF-κB, and pNF-κB were abolished after morin administration. This study suggests that morin treatment suppressed vincristine-induced neuropathic pain by protecting the sciatic nerve and inhibiting inflammation through NF-κB pathway.

Sevoflurane anesthesia impairs metabotropic glutamate receptor-dependent long-term depression and cognitive functions in senile mice.

AIM: Postoperative cognitive dysfunction is often observed in older patients. Previous reports described the link between postoperative cognitive dysfunction and general anesthetics, such as sevoflurane, but the exact mechanism remains unclear. We therefore sought to characterize the effects of sevoflurane on hippocampal-dependent cognitive functions, as well as hippocampal plasticity, and to delineate the underlying mechanisms. METHODS: Behavioral assays including the novel object recognition test and the Morris water maze test were carried out to assess the cognitive performance of control and sevoflurane-exposed mice. Electrophysiological recordings were carried out to evaluate the sevoflurane-induced changes of synaptic plasticity in the hippocampus. Furthermore, western blot assay was utilized to quantitatively assess the altered protein expression resulting from sevoflurane exposure. RESULTS: Sevoflurane anesthesia impaired cognitive functions, as well as metabotropic glutamate receptor-dependent long-term depression, through elevated surface expression of small conductance calcium-activated potassium type 2 channels. Blockage of calcium-activated potassium type 2 channels reversed the sevoflurane-induced deficits at both cellular and behavioral levels. CONCLUSIONS: Sevoflurane anesthesia impaired metabotropic glutamate receptor-dependent long-term depression and thereby affected cognitive functions in old mice. Inhibitory modulators of calcium-activated potassium type 2 channels might prevent cognitive decline elicited by sevoflurane. Geriatr Gerontol Int 2019; 19: 357-362.

Neonatal exposure to sevoflurane caused cognitive deficits by dysregulating SK2 channels and GluA2-lacking AMPA receptors in juvenile rat hippocampus.

Anesthetics exposure to neonates leads to impairment of hippocampal synaptic plasticity and cognitive functions later in life. This phenomenon complies with the concept of metaplasticity: a priming stimulation can affect induction of synaptic plasticity mins or days later. We aimed to understand whether small conductance Ca2+-activated potassium channel type2 (SK2) and subunit composition of AMPA receptors are altered and contribute to sevoflurane-induced metaplasticity. To fulfill this goal, we exposed neonatal rats (postnatal day 7) to 2% sevoflurane for 2 h (sevoflurane rats) and examined synaptic plasticity in the hippocampus and cognitive function in juvenile rats (postnatal day 30-35). We observed that the juvenile sevoflurane rats showed elevation in the threshold for LTP induction, facilitation of LTD induction, and cognitive dysfunctions. Meanwhile, these rats also exhibited increased surface expression of SK2 and enhanced synaptic recruitment of GluA2-lacking AMPA receptors, which possess stronger inward rectification. Blocking SK2 eliminated inward rectification of AMPA receptors in juvenile sevoflurane rats. Interestingly, blocking either SK2 channels or GluA2-lacking AMPA receptors normalized LTP, LTD, and spatial memory in juvenile sevoflurane rats. Our data indicate that neonatal sevoflurane anesthesia have negative impact on cognitive function extended to juvenile rats probably through increasing surface expression of SK2 and synaptic recruitment of GluA2-lacking AMPA receptors. This study provides a new sight for sevoflurane induced metaplasticity.

MiR-145 ameliorates neuropathic pain via inhibiting inflammatory responses and mTOR signaling pathway by targeting Akt3 in a rat model.

Neuropathic pain perplexes a large population of patients with various diseases. Inflammation plays a key role in the physiopathology of neuropathic pain. Anti-inflammatory can be a promising strategy to treat neuropathic pain. We generated a chronic constriction injury rat model to mimic neuropathic pain by ligating the left ischiadic nerves of rats. Then we performed intrathecal injection of miR-145 mimics to treat these rats for seven consecutive days. Pain behavior tests including mechanical allodynia and thermal hyperalgesia, pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were analyzed. Quantitative polymerase chain reaction and immunoblotting were performed to detect the changes of signaling pathway after miR-145 mimic treatment. Targeting of Akt3 by miR-145 was studied by dual-luciferase reporter gene assays. MiR-145 mimics injection significantly mollified both mechanical allodynia and thermal hyperalgesia in rats, and down-regulated secretion of TNF-α, IL-1ß and IL-6. We confirmed that miR-145 directly targeted Akt3, inhibiting NF-κB and mTOR downstream genes in rat dorsal root ganglia. MiR-145 can mollify neuropathic pain in a chronic constriction injury rat model by reducing inflammation and ion channel overexpression through Akt3/mTOR and Akt3/NF-κB signaling pathways.

NaHS Protects against the Impairments Induced by Oxygen-Glucose Deprivation in Different Ages of Primary Hippocampal Neurons.

Brain ischemia leads to poor oxygen supply, and is one of the leading causes of brain damage and/or death. Neuroprotective agents are thus in great need for treatment purpose. Using both young and aged primary cultured hippocampal neurons as in vitro models, we investigated the effect of sodium hydrosulfide (NaHS), an exogenous donor of hydrogen sulfide, on oxygen-glucose deprivation (OGD) damaged neurons that mimick focal cerebral ischemia/reperfusion (I/R) induced brain injury. NaHS treatment (250 µM) protected both young and aged hippocampal neurons, as indicated by restoring number of primary dendrites by 43.9 and 68.7%, number of dendritic end tips by 59.8 and 101.1%, neurite length by 36.8 and 66.7%, and spine density by 38.0 and 58.5% in the OGD-damaged young and aged neurons, respectively. NaHS treatment inhibited growth-associated protein 43 downregulation, oxidative stress in both young and aged hippocampal neurons following OGD damage. Further studies revealed that NaHS treatment could restore ERK1/2 activation, which was inhibited by OGD-induced protein phosphatase 2 (PP2A) upregulation. Our results demonstrated that NaHS has potent protective effects against neuron injury induced by OGD in both young and aged hippocampal neurons.

Involvement of spinal glutamate transporter-1 in the development of mechanical allodynia and hyperalgesia associated with type 2 diabetes.

Little is known about the effects of the development of type 2 diabetes on glutamate homeostasis in the spinal cord. Therefore, we quantified the extracellular levels of glutamate in the spinal cord of Zucker diabetic fatty (ZDF) rats using in vivo microdialysis. In addition, protein levels of glutamate transporter-1 (GLT-1) in the spinal cord of ZDF rats were measured using Western blot. Finally, the effects of repeated intrathecal injections of ceftriaxone, which was previously shown to enhance GLT-1 expression, on the development of mechanical allodynia and hyperalgesia as well as on basal extracellular level of glutamate and the expression of GLT-1 in the spinal cord of ZDF rats were evaluated. It was found that ZDF rats developed mechanical hyperalgesia and allodynia, which were associated with increased basal extracellular levels of glutamate and attenuated levels of GLT-1 expression in the spinal cord, particularly in the dorsal horn. Furthermore, repeated intrathecal administrations of ceftriaxone dose-dependently prevented the development of mechanical hyperalgesia and allodynia in ZDF rats, which were correlated with enhanced GLT-1 expression without altering the basal glutamate levels in the spinal cord of ZDF rats. Overall, the results suggested that impaired glutamate reuptake in the spinal cord may contribute to the development of neuropathic pains in type 2 diabetes.

Impacts of Thermal Atomic Layer-Deposited AlN Passivation Layer on GaN-on-Si High Electron Mobility Transistors.

Thermal atomic layer deposition (ALD)-grown AlN passivation layer is applied on AlGaN/GaN-on-Si HEMT, and the impacts on drive current and leakage current are investigated. The thermal ALD-grown 30-nm amorphous AlN results in a suppressed off-state leakage; however, its drive current is unchanged. It was also observed by nano-beam diffraction method that thermal ALD-amorphous AlN layer barely enhanced the polarization. On the other hand, the plasma-enhanced chemical vapor deposition (PECVD)-deposited SiN layer enhanced the polarization and resulted in an improved drive current. The capacitance-voltage (C-V) measurement also indicates that thermal ALD passivation results in a better interface quality compared with the SiN passivation.

AlGaN/GaN MISHEMTs with AlN gate dielectric grown by thermal ALD technique.

Recently, AlN plasma-enhanced atomic layer deposition (ALD) passivation technique had been proposed and investigated for suppressing the dynamic on-resistance degradation behavior of high-electron-mobility transistors (HEMTs). In this paper, a novel gate dielectric and passivation technique for GaN-on-Si AlGaN/GaN metal-insulator-semiconductor high-electron-mobility transistors (MISHEMTs) is presented. This technique features the AlN thin film grown by thermal ALD at 400°C without plasma enhancement. A 10.6-nm AlN thin film was grown upon the surface of the HEMT serving as the gate dielectric under the gate electrode and as the passivation layer in the access region at the same time. The MISHEMTs with thermal ALD AlN exhibit enhanced on/off ratio, reduced channel sheet resistance, reduction of gate leakage by three orders of magnitude at a bias of 4 V, reduced threshold voltage hysteresis of 60 mV, and suppressed current collapse degradation.

Connection changes in somatosensory cortex induced by different doses of propofol.

BACKGROUND: The mechanism by which general anesthetics, widely used in clinical practice for over 160 years, effects on sensory responsiveness has been unclear until now. In the present study, the authors sought to explore the effect of different doses of propofol on somatosensory cortex by whisker stimulation in rats. METHODS: In a fixed cage, rats were anesthetized with propofol 80 mg/kg intraperitoneally and then cathetered tail vein with 23-gauge metal needle connected with a pump. Two holes (2 mm diameter) were drilled and recording electrodes implantated in the primary somatosensory cortex barrel field (S1BF) and secondary somatosensory cortex (S2). The extracellular (20 rats) and intracellular (8 rats) recordings were used to test the neuron activity in both cortices at different doses of propofol (20, 40 and 80 mg/kg/h) through tail vein by pump. Meantime, vibrissal, olfactory, corneal responses (VOCR, sedation), and tail-pinch response (TRP, analgesia) were tested every 10 min during the doses of propofol 20, 40 and 80 mg/kg/h. RESULTS: VOCR and TRP were depressed by propofol in a dose-dependent manner. The amplitude by whisker stimulation in S1BF was stronger and the peak latency was shorter compared with that of in S2. The response latency of S1BF and S2 was increased by raising infusion rate of propofol with the response latency in S2 being longer than that in S1BF at the same doses of propofol. The cross-correlation between S1BF and S2 decreased as the propofol infusion rate increased. The input resistance was higher by increasing infusion rate of propofol. CONCLUSION: The sedation and analgesia effects of propofol were dose-dependent. Both the connectivity and instinctive oscillation between S1BF and S2 were proportionally modulated by the different doses of propofol.

The neurotoxicity of ß-amyloid peptide toward rat brain is associated with enhanced oxidative stress, inflammation and apoptosis, all of which can be attenuated by scutellarin.

This study was designed to investigate the processes underlying the neurotoxicity induced by ß-amyloid peptide (Aß) in the rat brain, as well as to examine whether scutellarin (Scu) can prevent this neurotoxicity. Thirty Wistar rats were randomly divided into 3 groups, i.e., untreated (control), treated with Aß and treated with both Aß and Scu. The treated rats were subjected to bilateral intracerebroventricular injection of Aß(25-35) with or without subsequent dietary exposure to Scu. Learning and memory were assessed with the Morris water maze test; the activities of superoxide dismutase (SOD) and monoamine oxidase (MAO) were assayed biochemically; expression of the interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) proteins was determined by immunohistochemistry; and neuronal apoptosis was detected with Annexin staining followed by flow cytometry. The animals treated with Aß exhibited impaired learning and memory; reduced SOD and elevated MAO activity, elevated protein levels of IL-1ß, IL-6 and TNF-α; and a higher percentage of apoptotic neurons in the brain. Interestingly, all of these effects were ameliorated by administration of Scu. These findings indicate that the deficits in learning and memory demonstrated by the rats receiving Aß are due to elevated oxidative stress and inflammation, which result in apoptosis and that Scu may prevent these deleterious effects.

Chemical form of metals in traditional medicines underlines potential toxicity in cell cultures.

ETHNOPHARMACOLOGICAL RELEVANCE: Mercury (Hg) and arsenic (As) are frequently found in traditional medicines as sulfides, such as cinnabar (HgS) and realgar (As(4)S(4)). There is a general perception that any medicinal use of such metal-containing remedies is unacceptable. An opposing opinion is that different chemical forms of arsenic and mercury have different toxic potentials. AIM OF THE STUDY: To clarify this question, cinnabar, realgar, and cinnabar- and realgar-containing traditional medicine An-Gong-Niu-HuangWan (AGNH), were compared to well-known mercurials (HgS, HgCl(2) and MeHg) and arsenicals (As(2)S(2), As(2)O(3), NaAsO(2), and Na(2)HAsO(4)) for their cytotoxicity in human and rodent cell lines. MATERIALS AND METHOD: Cultured cells derived from target organs such as brain (HAPI) and liver (Hep3B, HepG2 and TRL1215) were treated with chemicals for 48 h and cytotoxicity was determined by the MTS assay. RESULTS: MeHg was most toxic with LC(50) of 4-20µM, followed by NaAsO(2) (LC(50), 25-250 µM) and HgCl(2) (LC(50,) 50-100 µM), Na(2)HAsO(4)(LC(50), 60-400µM), As(2)O(3)(LC(50), 30-900 µM), and As(2)S(2) (LC(50), 100-500 µM). In comparison, the LC(50) of realgar ranged from 250 to1500 µM; whereas cinnabar or HgS were approximately 20,000 µM and the toxicity of AGNH was in the range of 1500-8000 µM. Approximately 5000-fold differences exist between MeHg and HgS, and over 10-fold differences exist between NaAsO(2) and As(4)S(4). CONCLUSIONS: Chemical forms of metals are important factor in determining their toxicity in traditional medicines, both cinnabar and realgar are much less toxic than well-known mercurial and arsenicals.

[Analysis of Belamcanda chinensis with space flight mutagenesis by FTIR].

The amorphous active components of the space mutagenesis Belamcanda chinensis and the ground group were measured, compared and analyzed. The purpose was to get a comprehensive understanding of the changes in quality of the 4th generation space mutagenesis Belamcanda chinensis, accumulate data for further studies, and try to establish the quality criterions of space mutagenesis Belamcanda chinensis. The result shows that the FTIR spectra of the space sample are almost the same as that of the ground one in terms of the main absorption peaks positions and shapes, but there are obvious differences in intensities. The intensity of the absorption peak at 1 642 and 1 318 cm(-1) of the space group was remarkably enhanced than the ground group, but at 1 541, 1 456, 1 417 and 1 051 cm(-1) it was decreased compared to the ground group. At the same time, the peak at 1 642 cm(-1) of the stretching vibration of C=O, the characteristic absorption of the keto, was remarkably enhanced. The peaks at 1 541 and 1 456 cm(-1) were assigned to C-C groups, the peak at 1 417 cm(-1) was due to the -CH2- groups, the peak at 1 318 cm(-1) was the characteristic absorption of calcium oxalate monohydrate, and the peak at 1 051 cm(-1) was assigned to C-O groups. It was shown that the relative content of flavone was increased distinctly. Space mutation breeding is conducive to breeding new varieties of highly active ingredients, it is also one of the ways to innovate germplasm resources of Chinese medicines efficiently. The effect of the space group is expected to be enhanced than the ground group, but it needs to be proved through further research.

[Analysis of the 4th generation Scutellaria baicalensis Georgi with space mutagenesis via FTIR spectroscopy].

Determination and analysis for the Scutellaria baicalensis Georgi with space mutagenesis and the ground group were carried out with FTIR for the first time in order to fully understand the quality changes of the 4th generation of space mutagenesis of Scutellaria baicalensis Georgi and do further research. The result shows that for the FTIR spectra of the two samples the position and shape of main absorption peaks are approximately the same, indicating that the major components and the structures of space group remain intact, but the intensities of the absorption peaks are obviously different, with the intensities of the space group significantly enhanced compared to the ground group, especially for the flavonoid compounds (baicalin, baicalein, wogonoside, wogonin and wogonoside etc), which are the main active components of the Scutellaria baicalensis Georgi, the absorption peak intensities at 3391, 1655 and 1069 cm(-1) are obviously stronger than those of the ground group, so the contents of flavonoid compounds and other components are higher, and the amorphous active components are optimized. Space mutation breeding is conducive to breeding new varieties of highly active components, and it is also one of the ways to innovate Chinese medicines germplasm resources efficiently.

[Study on spaceflight mutagenesis Platycodon grandiflorum via FTIR].

OBJECTIVE: To establish a method for analyzing amorphous organic compound components of space Platycodon grandflorum rapidly. METHOD: FTIR was applied for measuring and comparing P. grandflorum of comparison group,the ground group and the 4" generation of space group. RESULT: Several active components (platycodin, polysaccharide etc.) contents of space group are increased obviously. CONCLUSION: The major components and the structures remained inextenso,and the effictive component contents are enhanced in the space P. grandiflorum. FTIR is a fast method to analyze the changes of amorphous organic compound components of the space traditional Chinese medicines.

[Research on the fourth generation of Saposhnikovia divaricata by XRF].

To cultivate oriented new varieties, Saposhnikovia divaricata seeds were carried by Shenzhou "3" satellite and filtered when they were being brought back. In the present paper, X-ray fluorescence(XRF) was used to mensurate and analyze the contents of elements of the two samples from the ground group and the 4th generation of space Saposhnikovia divaricata (space group) that have advantages in branches and leaves and yields. The contents of the main mineral elements in the two samples are the same basically. But the contents of the elements Zn, Fe, Mn and Cu from the outer group are higher than the ground group. Especially the contents of Zn, Fe, Mn and Cu concerning the curative effect in the space group increase 4.39, 1.23, 0.84 and 0.9 times as compared to the ground group. In the space group the contents and proportions of the mineral elements are improved and optimized. XRF method can be used for overall element analysis of and research on Chinese herbal medicines. Space flight breeding is an effective method for the selection of new Saposhnikovia divaricata breed.

[Measurement and analysis of platycodon grandiflorum with space flight mutagenesis breeding by XRF].

X-ray fluorescence spectrum (XRF) analytic method was used to analyze and compare the contents of various mineral elements in the ground group platycodon grandiflorum, the comparison group platycodon grandiflorum and the fourth generation platycodon grandiflorum with space flight mutagenesis breeding. The result indicated that the contents of microelements Zn, Mn and Fe in the outer space group increase by 1.9, 2.4 and 0.6 times respectively, compared with those in the ground group. Microelements Zn, Mn and Fe concern curative effect such as expectorant effect in the Chinese traditional medicine. And the elements Zn and Mn increase by 0.6 and 1.9 times respectively, compared with the comparison group. The outer space group is closer and/or superior to the comparison group compared with the ground group. To conclude, the performance of the outer space group platycodon grandiflorum was upgraded obviously. X-ray fluorescence spectrum analytic method has many advantages, such as quickness, simpleness, high sensitivity, wide measure range, and easy reappearance etc. The method could be applied to the mensuration and analysis of the other traditional Chinese medicines which could be ground into powder.