Treatment of radiation-induced brain injury with bisdemethoxycurcumin.

Radiation therapy is considered the most effective non-surgical treatment for brain tumors. However, there are no available treatments for radiation-induced brain injury. Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin that has anti-proliferative, anti-inflammatory, and anti-oxidant properties. To determine whether BDMC has the potential to treat radiation-induced brain injury, in this study, we established a rat model of radiation-induced brain injury by administering a single 30-Gy vertical dose of irradiation to the whole brain, followed by intraperitoneal injection of 500 µL of a 100 mg/kg BDMC solution every day for 5 successive weeks. Our results showed that BDMC increased the body weight of rats with radiation-induced brain injury, improved learning and memory, attenuated brain edema, inhibited astrocyte activation, and reduced oxidative stress. These findings suggest that BDMC protects against radiation-induced brain injury.

Systematic Administration of B Vitamins Alleviates Diabetic Pain and Inhibits Associated Expression of P2X3 and TRPV1 in Dorsal Root Ganglion Neurons and Proinflammatory Cytokines in Spinal Cord in Rats.

Background: Treatment of diabetic neuropathic pain (DNP) continues to be a major challenge, and underlying mechanisms of DNP remain elusive. We investigated treatment effects of B vitamins on DPN- and DNP-associated alterations of neurochemical signaling in the nociceptive dorsal root ganglion (DRG) neurons and the spinal cord in rats. Methods: DNP was produced in male, adult, Sprague Dawley rats by single i.p. streptozotocin (STZ). Western blot analysis and immunohistochemistry were used to analyze protein expressions in DRG and ELISA to measure the proinflammatory cytokines in the spinal cord. Behaviorally expressed DNP was determined by measuring the sensitivity of hindpaw skin to mechanical and thermal stimulation. Results: There were 87.5% (77/88) rats which developed high blood glucose within 1-2 weeks following STZ injection. Of which, 70.13% (n = 54/77) animals exhibited DNP manifested as mechanical allodynia and/or thermal hyperalgesia. Intraperitoneal administration of vitamins B1/B6/B12 (100/100/2 mg/kg, one or multiple doses) significantly attenuated DNP without affecting the blood glucose. Expressions of P2X3 and TRPV1 in CGRP-positive and IB4-positive DRG neurons as well as the interleukin-1ß, tumor necrosis factor-α, and nerve growth factor in the lumbar spinal cord were greatly increased in DNP rats. Such DNP-associated neurochemical alterations were also greatly suppressed by the B-vitamin treatment. Conclusions: B-vitamin treatment can greatly suppress chronic DNP and DNP-associated increased activities of P2X3 and TRPV1 in DRG and the spinal proinflammatory cytokines, which may contribute to the pathogenesis of DNP. Systematic administration of B vitamins can be a strategy for DNP management in clinic.

Mitochondrial tRNAIle A4317G mutation may be associated with hearing impairment in a Han Chinese family.

Mutations in the mitochondrial genome have been identified to be associated with hearing loss. The aim of the present study was to investigate the role of mitochondrial DNA (mtDNA) variants in a Chinese family with hearing loss. Polymerase chain reaction (PCR)­Sanger sequencing was used to screen the mtDNA variants and nuclear genes [gap junction protein ß2 (GJB2) and transfer (t)RNA 5­methylaminomethyle­2­thiouridylate methyltransferase (TRMU)]; in addition, the mtDNA copy number was determined by quantitative PCR. The present study characterized the molecular features of a Chinese family with maternally­inherited hearing loss and identified mtDNA A1555G and tRNAIle A4317G mutations. The A4317G mutation was localized at the TΨC arm of tRNAIle (position 59) and created a novel base­pairing (G59­C54), which may alter the secondary structure of the tRNA. In addition, patients carrying the A4317G mutation exhibited a lower mtDNA copy number compared with the controls, suggesting that this mutation may cause mitochondrial dysfunction that is responsible for the deafness. However, no functional variants in the GJB2 and TRMU genes were detected. mtDNA A1555G and A4317G mutations may contribute to the clinical manifestation of hearing loss in this family.

Application of image guided technique in rhino-orbital related endoscopic surgery / 临床耳鼻咽喉头颈外科杂志

To review retrospectively six cases of rhino-orbital related endoscopic surgeries aided by Fusion electromagnetic system,to explore the indications and clinical value of image guided technique in endonasal endoscopic surgery.Retrospective research methods were used.In this study,six cases of nasal endoscopic sinus surgery using Fusion electromagnetic system were analyzed,including 1 nasal penetrating foreign body,2 optic nerve decompressions,1 orbital apex hemangioma,1 sieve frontal sinus cyst,1 intraorbital mass biopsy.The preparation time of navigation system,the accuracy of intraoperative positioning and surgical coherence,intraoperative and postoperative complications of surgery were recorded.The average preparation time was(8.13 ± 1.858)min.In the navigation,the sinus ostium,orbital cardboard,skull base,optic nerve,internal carotid artery and other important structures can be accurately located in all patients,while registrations had been accurate within 1 mm.Six patients were successfully operated by image guided technique.There was no intracranial or intraorbital complications due to intraoperation error.Image guided technique allows for a truely microinvasive and accurate rhino-orbital related endoscopic surgeries.It requires less preoperative preparation time,has high surgical navigation accuracy,improves the surgical coherence and safety,and reduces the surgical complicationgs.However,as an auxiliary tool,it can not replace the surgeon's anatomical knowledge,surgical training and clinical experience.

Effect of magnesium-calcium alloy extract on matrix metalloproteinase-9 and matrix metalloproteinase inhibitor-3 in human colonic epithelial cells / 新乡医学院学报

Objective To investigate the effect of different concentrations of magnesium-calcium alloy extract on the expression of matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinase-3 (TIMP3) in human colonic epithelial NCM460 cells.Methods The different concentrations of extracts (the volume fraction was 10％,50％ and 100％ respectively) were made with magnesium-calcium alloy.The 5 × 106 L-1 NCM460 suspension was randomly divided into control group,experimental group 1,experimental group 2 and experimental group 3.The cells in the control group were cultured by 2 000 μL high glucose Dulbecco's modified Eagle's medium (containing 10％ volume fraction of fetal bovine serum).The cells in the experimental group 1,2 and 3 were cultured by 2 000 μL magnesium-calcium alloy extract with volume fraction of 10％,50％ and 100％ respectively.The expressions of MMP9 and TIMP3 mRNA in NCM460 cells was detected by real-time fluorescence quantitative polymerase chain reaction,and the expression of MMP9 and TIMP3 protein in NCM460 cells was detected by Western blot at after one,three and five days of cultivation respectively.Results The expression of MMP9 mRNA and TIMP3 mRNA in NCM460 cells of the experimental group 1,2 and 3 was significantly lower than that in the control group after one day of cultivation (P ＜ 0.05).After three and five days of cultivation,the expression of MMP9 mRNA in NCM460 cells of the experimental group 1 was significantly lower than that in the control group (P ＜ 0.05),but the expression of MMP9 mRNA in the NCM460 cells of the experimental group 2 and 3 was significantly higher than that in the control group and the experimental group 1 (P ＜ 0.05).The expression of MMP9 mRNA in NCM460 cells of the experimental group 3 was significantly higher than that in the experimental group 2 after five days of cultivation (P ＜ 0.05).The expression of MMP9 mRNA in NCM460 cells of the experimental group 1,2 and 3 after three and five days of cultivation was significantly higher than that after one day of cultivation(P ＜ 0.05).There was no significant difference in the expression of MMP9 mRNA in NCM460 cells of the experimental group 1 between three and five days of cultivation (P ＞ 0.05).The expression of MMP9 mRNA in NCM460 cells of the experimental group 2 and 3 after five days of cultivation was significantly higher than that after three days of cultivation(P ＜ 0.05).The expression of TIMP3 mRNA in NCM460 cells of the experimental group 2 and 3 was significantly higher than that in the experimental group 1 after one day of euhivation (P ＜ 0.05).After three days of cultivation,the expression of TIMP3 mRNA in NCM460 cells of the experimental group 1,2 and 3 was significantly lower than that in the control group (P ＜ 0.05);the expression of TIMP3 mRNA in NCM460 cells of the experimental group 2 was significantly lower than that in the experimental group 1 and 3 (P ＜ 0.05).After five days of cultivation,the expression of TIMP3 mRNA in NCM460 cells of the experimental group 1,2 and 3 was significantly higher than that in the control group (P ＜ 0.05).The expression of TIMP3 mRNA in NCM460 cells after three and five days of cultivation was significantly higher than that after one day of cultivation (P ＜ 0.05),and the expression of TIMP3 after five days of cultivation was significantly higher than that after three days of cultivation in the experimental group 1 (P ＜ 0.05).The expression of TIMP3 mRNA in NCM460 cells after three days of cultivation was significantly lower than that after one day of cultivation (P ＜ 0.05),and the expression of TIMP3 after five days of cultivation was significantly higher than that after one and three days of cultivation in the experimental group 2 (P ＜ 0.05).The expression of TIMP3 mRNA in NCM460 cells after five days of cultivation was significantly higher than that after one and three days of cultivation in the experimental group 3 (P ＜ 0.05).After five days of cultivation,there was no significant difference in the expression of MMP9 protein in NCM460 cells between the experimental group 1 and control group (P ＞ 0.05),the expression of MMP9 protein in NCM460 cells of the experimental group 2 and 3 was significantly higher than that in the control group and the experimental group 1 (P ＜ 0.05),but there was no significant difference in the expression of MMP9 protein in NCM460 cells between the experimental group 2 and 3 (P ＞ 0.05).After five days of cultivation,the expression of TIMP3 protein in NCM460 cells of the experimental group 1,2 and 3 was significantly higher than that in the control group (P ＜0.05);but there was no significant difference in the expression of TIMP3 protein in NCM460 cells among the experimental group 1,2and 3 (P ＞ 0.05).Conclusions The high concentration of magnesium-calcium alloy extract has certain influence on the expression of MMP9 and TIMP3 gene in NCM460 cells,which may lead to the early inflammatory reaction,and the mechanism may be related to the calcium ion concentration in the extract.

Primary drug resistance among newly reported human immunodeficiency virus infected individuals in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province in 2015 / 中华传染病杂志

Objective To determine the prevalence of human immunodeficiency virus (HIV) primary drug resistance (HIV-PDR) in newly reported HIV-infected individuals in Dehong Prefecture,Yunnan Province in 2015.Methods Newly reported HIV-positive patients who had viral load ≥ 1 000 copies/mL from January to November in 2015 were tested for HIV-PDR by reverse transcriptionpolymerase chain reaction (RT-PCR) and HIV pol gene sequencing.HIV-PDR was determined according to the Surveillance Drug Resistance Mutations (SDRM) list of Stanford University,which was recommended by World Health Organization (WHO) in 2009.Results A total of 322 newly reported HIV-infected cases whose pol gene was successfully amplified were included in the final analysis.Of them,211 (65.5％) were male,and 229 (71.1％) were sexually transmitted.A total of 152 (47.2％) were Chinese.A total of 29 HIV subtypes were found,including type B (12.1％),type C (28.0％),type CRF01_AE (24.5％),type CRF07_BC (5.9％),type CRF08_BC (5.6％),type 62_BC (7.5％),type BC-new breakpoint (3.4％) and other subtypes (13％).Six patients (1.9％) were defined as primary resistance to HIV according to the WHO standard.Conclusions The prevalence of HIV-PDR is 1.9％ among newly reported HIV-infected individuals,which is relatively low in the studied area.But HIV-PDR surveillance should be strengthened in this area with the scaling up of antiretroviral therapy.

Structures, Phase Transformations, and Dielectric Properties of BiTaO4 Ceramics.

Low (α)- and high-temperature (ß) forms of BiTaO4 have attracted much attention due to their dielectric and photocatalytic properties. In the present work, a third form, the so-called HP-BiTaO4, was synthesized at high temperature and pressure. The phase evolution, phase transformations, and dielectric properties of α- and ß-BiTaO4 and HP-BiTaO4 ceramics are studied in detail. ß-BiTaO4 ceramics densified at 1300 °C with the microwave permittivity εr ≈ 53, the microwave quality factor Qf ≈ 12070 GHz, and the temperature coefficient of resonant frequency τf ≈ -200 ppm/°C. HP-BiTaO4 ceramics were synthesized at 5 GPa and 1300 °C followed by annealing at 600 °C. In contrast with the α phase, HP-BiTaO4 exhibited εr ≈ 195 at 1 kHz to 10 MHz, accompanied by a low dielectric loss of ∼0.004. The relation between structure and dielectric properties is discussed in the context of Shannon's additive rule and bond theory.

Inhibition of YAP/TAZ Activity in Spinal Cord Suppresses Neuropathic Pain.

UNLABELLED: Neuropathic pain, often caused by nerve injury, is a major clinical challenge. Mechanisms that underlie neuropathic pain remain elusive and effective medications are limited. Numerous investigations of pain mechanisms have focused on alterations and phenotypic switches of the nociceptive transmitters and modulators, as well as on their receptors and downstream signaling pathways that have already exerted roles in the pain processes of mature nervous systems. We have demonstrated recently that nerve injury may elicit neuronal alterations that recapitulate events occurring during development. Signaling of the representative activated molecule Wnt thus becomes a trigger for the development of neuropathic pain and is a potential therapeutic target. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the ß-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status in rats. Peripheral nerve injury causes rapid-onset and long-lasting nuclear accumulation of YAP/TAZ/ß-catenin in the spinal dorsal horn. Spinal inhibition or knock-down of either YAP or TAZ suppresses mechanical allodynia induced by nerve injury or the pain initiators lysophosphatidic acid and Wnt3a. Promoting the nuclear accumulation of YAP/TAZ leads to mechanical hypersensitivity in naive animals. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/ß-catenin and can greatly suppress neuropathic pain and the associated neurochemical alterations. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening for potent analgesics for the treatment of neuropathic pain. SIGNIFICANCE STATEMENT: Mechanisms that underlie neuropathic pain remain elusive. We have demonstrated recently that nerve injury can activate Wnt signaling, which becomes a trigger for the development of neuropathic pain. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the ß-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/ß-catenin and can greatly suppress neuropathic pain. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening of potent analgesics for the treatment of neuropathic pain.

Activation of the cAMP-PKA signaling pathway in rat dorsal root ganglion and spinal cord contributes toward induction and maintenance of bone cancer pain.

The objective of this study was to explore the role of cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling in the development of bone cancer pain in rats. Female Sprague-Dawley rats (N=48) were divided randomly into four groups: sham (n=8), tumor cell implantation (TCI) (n=16), TCI+saline (n=8), and TCI+PKA inhibitor (n=16). Bone cancer-induced pain behaviors - thermal hyperalgesia and mechanical allodynia - were tested at postoperative days -3, -1, 1, 3, 5, 7, 10, and 14. A PKA inhibitor, Rp-cAMPS (1 mmol/l/20 µl), was injected intrathecally on postoperative days 3, 4, and 5 (early phase) or 7, 8, and 9 postoperative days (late phase). The expression of PKA mRNA in dorsal root ganglia (DRG) was detected by reverse transcription-PCR. The concentration of cAMP and activity of PKA in DRG and spinal cord were measured by enzyme-linked immunosorbent assay. TCI treatment induced significant pain behaviors, manifested as thermal hyperalgesia and mechanical allodynia. Spinal administration of the PKA inhibitor Rp-cAMPS during the early phase and late phase significantly delayed or reversed, respectively, TCI-induced thermal hyperalgesia and mechanical allodynia. TCI treatment also led to obvious tumor growth and bone destruction. The level of PKA mRNA in the DRG, as well as the concentration of cAMP and the activity of PKA, in both the DRG and spinal cord were significantly increased after TCI treatment (P<0.01). We conclude that the inhibition of the cAMP-PKA signaling pathway may reduce bone cancer pain.

[Perioperative airway management for the treatment of atlantoaxial surgical lysis and fixation through transoral approach].

OBJECTIVE: To explore the perioperative airway management for transoral surgical lysis in patients with irreducible atlantoaxial dislocation and posterior atlantoaxial or occipitocervical fixation. METHODS: Thirty patients undergoing surgical lysis through transoral approach with oral endotracheal intubation (OEI group) between September 2009 and June 2010 were recruited. And another 31 patients underwent transoral surgical lysis from December 2008 to August 2009 with percutaneous dilatational tracheostomy (PDT group). The time interval from artificial airway establishment to start of operation, the duration of nasogastric feeding, the incidence of respiratory complications and the postoperative length of hospital stay were compared between two groups. RESULTS: The time interval from artificial airway establishment to the start of operation in the OEI group was significantly shorter than that in the PDT group [(39 ± 15) vs (58 ± 16) min, P < 0.01]. The duration for nasogastric feeding in the OEI group was significantly shorter than that in the PDT group [(6.0 ± 1.2) vs (7.9 ± 0.3) days, P < 0.01]. And the postoperative length of hospital stay was also shorter in the OEI group than that in the PDT group [(9.5 ± 1.7) vs (11.8 ± 3.4) days, P < 0.01]. CONCLUSION: The management of perioperative airway with oral endotracheal intubation may avoid the complications of PDT, improve the utilizing efficiency of operating rooms and shorten the postoperative length of hospital stay.

Effect of intraoperative using cell saver on blood sparing and its impact on coagulation function / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the effectiveness of using cell saver (CS) during surgery on blood sparing and its impact on patient's hematology and coagulation function.</p><p><b>METHODS</b>One-hundred and thirty-eight patients undergoing elective surgery were recruited for intraoperative blood salvage using CS. Blood routine, blood chemistry and coagulation function were measured before surgery, after infusion of salvaged blood and postoperative day 1, respectively.</p><p><b>RESULTS</b>In total, 112,056 ml of packed red blood cells were collected, with a mean value of 812 ml per patient. The percentage of autologous blood transfusion volume to the total blood transfusion volume was from 48% to 89%. Allogenic blood transfusion rate was from 5% to 100%. Compared with the values before surgery, the hemoglobin concentration, platelet count, plasma total protein and fibrinogen concentration decreased significantly after the transfusion of salvaged blood and the first postoperative day (P < 0.05 or P < 0.01), while the prothrombin time was significantly prolonged (P < 0.05).</p><p><b>CONCLUSIONS</b>The use of CS during surgery can, to a certain extent, reduce the requirement of allogenic blood. However, reinfusion of large amount of salvaged blood may affect coagulation function.</p>

Influence of obesity on pharmacokinetics and pharmacodynamics of isoflurane / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the effect of obesity on pharmacokinetics and pharmacodynamics of isoflurane.</p><p><b>METHODS</b>Twenty-six patients undergoing cholecystectomy were divided into obese group (Group A, BMI > or = 27, n = 13) and normal body weight group (Group N, BMI < or = 24, n = 13) according to body mass index (BMI). All patients were given to the same isoflurane anesthesia. Inspired and end-expired concentrations of isoflurane were monitored and uptake fraction of isoflurane were calculated.</p><p><b>RESULTS</b>Isoflurane concentrations of vaporizer in Group A [(1.8 +/- 0.3)%] were evidently higher than those in Group N [(1.5 +/- 0.1)%] at all observed points (P < 0.05 or P < 0.01). Uptake fraction of isoflurane in Group A were higher than those in Group N at observed points (P < 0.05, P < 0.01 or P < 0.001), but there were no differences in the time when isoflurane concentration was lowered to 50% and awake time between the two groups after discontinuing inhaling isoflurane.</p><p><b>CONCLUSIONS</b>Obese patients demand higher inspired concentration and uptake of isoflurane than those in normal weight patients but discharge of isoflurane was influenced by obesity within the observed period of (66 +/- 33) min.</p>