Simvastatin alleviates inflammation and oxidative stress in rats with cerebral hemorrhage through Nrf2-ARE signaling pathway.

OBJECTIVE: To investigate the regulatory effects of simvastatin on the inflammation and oxidative stress in rats with cerebral hemorrhage through the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway. MATERIALS AND METHODS: A total of 120 healthy male rats weighing 280-300 g and 7-8 weeks old were selected to establish the traumatic brain injury (TBI) model. Rats were divided into group A (trauma operation, n=30), group B (no treatment, n=30), group C (drug administration after trauma operation, n=30), and group D (no trauma operation, drug administration, n=30). Cerebral edema content in brain tissues was measured by calculating the dry and wet weight. Neurological dysfunction was scored using the Garcia method. Positive levels of the Toll-like receptor 4 (TLR4) and interleukin-1ß (IL-1ß) were qualitatively analyzed via immunohistochemistry. Protein levels of TLR4 and IL-1ß were quantitatively analyzed via Western blotting. Moreover, the brain injury volume and neuronal apoptosis were evaluated via Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. At 48 h after injury, activities of superoxide dismutase (SOD), reduced glutathione (GSH), and oxidized glutathione (GSSG) in brain tissues were detected, and levels of malondialdehyde (MDA) and nitric oxide (NO) were detected using the enzyme activity assay kits. Finally, relative levels of the Nrf2-ARE signaling pathway and its downstream molecules heme oxygenase-1 (HO-1) and NAD (P)H dehydrogenase, quinone 1 (NQO1) were detected via reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting. RESULTS: Compared with those in group B, cerebral edema content in brain tissues significantly increased (p<0.05), the neurological dysfunction score significantly declined (p<0.05), and protein levels of TLR4 and IL-1ß were significantly upregulated in group A (p<0.05). In group C, relative levels of TLR4 and IL-1ß were down-regulated, cerebral edema content decreased, and the neurological dysfunction score significantly increased (p<0.05). After 48 h, activities of SOD, reduced GSH and GSSG and levels of MDA and NO all increased, and levels of MDA and NO declined in group C (p<0.05). Western blotting and RT-PCR showed that simvastatin could increase the transcriptional level of Nrf2. After simvastatin intervention, expression levels of downstream molecules HO-1 and NQO1 were upregulated. CONCLUSIONS: Simvastatin alleviates TLR4-mediated inflammatory injury, promotes neurological recovery and resists oxidative stress through the Nrf2-ARE signaling pathway, thus exerting a neuroprotective effect in TBI.

[Nasopharyngeal low grade papillary adenocarcinoma with squamous differentiation：a case report].

Summary Low grade papillary adenocarcinoma is especially rare tumor in nasopharynx. Here we reported a patient who had low grade papillary adenocarcinoma of the nasopharynx and was diagnosed by pathology. The patient complained for bilateral nasal congestion for 10 years and was hospitalized in recent 3 years. The patient received nasopharyngeal tumor resection, and the postoperative pathological examination showed low grade nasopharyngeal papillary adenocarcinoma with squamation. The patient was followed up for 9 months without recurrence or metastasis. We reported this case and reviewed the relevant literature in order to improve the diagnosis and treatment of this disease..

Effect of miR-130a on neuronal injury in rats with intracranial hemorrhage through PTEN/PI3K/AKT signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effect of micro-ribonucleic acid (miR)-130a on neuronal injury in rats with intracerebral hemorrhage (ICH) through the phosphatase and tensin homolog deleted on chromosome ten/phosphatidylinositol 3-hydroxy kinase/protein kinase B (PTEN/PI3K/AKT) signaling pathway. MATERIALS AND METHODS: A total of 30 healthy male rats were randomly divided into three groups, including the blank control group, ICH model group (ICH group) and ICH model + miR-130a treatment group (miR-130a treatment group). The differences in neurological injury, the number of apoptotic cells in brain tissues, the activity of Caspase-9 and protein expressions of PTEN/PI3K/AKT were analyzed among the three groups, respectively. RESULTS: Neurological function was normal without injury in the control group. However, the neurological injury was severe in the ICH group and mild in the miR-130a treatment group. There were statistically significant differences in neurological function in the control group relative to those of the ICH group and miR-130a treatment group (p<0.05). Meanwhile, the neurological injury was markedly milder in the miR-130a treatment group than that of the ICH group, showing a statistically significant difference (p<0.05). The number of apoptotic cells was remarkably smaller in the control group when compared with the ICH group and miR-130a treatment group. However, it was markedly larger in the ICH group than that of the miR-130a treatment group, showing significant differences (p<0.05). The activity of Caspase-9 was significantly lower in the control group than ICH group and miR-130a treatment group (p<0.05). However, it increased remarkably in the ICH group compared with that of the miR-130a treatment group (p<0.05). Moreover, the protein level of PTEN in the ICH group was significantly higher than control group and miR-130a treatment group, displaying statistically significant differences (p<0.05). However, no marked difference in the protein level of PTEN was observed between the control group and miR-130a treatment group (p>0.05). The protein levels of the phosphorylated 3-hydroxy kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) were remarkably lower in the ICH group than those of the control group and miR-130a treatment group, displaying statistically significant differences (p<0.05). However, they were remarkably higher in the miR-130a treatment group than that of the control group (p<0.05). CONCLUSIONS: MiR-130a promotes neuronal growth in brain tissues in ICH rats and alleviates neuronal injury after ICH through the PTEN/PI3K/AKT signaling pathway. Our findings suggest that miR-130a exerts important clinical significance in the treatment of ICH.

[The preliminary report of a registration clinical trial of proton and heavy ion irradiation].

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions: IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

[The progress of the IL-12 cytokine family in allergic rhinitis].

As the IL-12 family plays an important role in immune regulation, it arouses the attention of the researchers increasingly. There are mainly four members in the IL-12 family, including IL-12, IL-23, IL-27 and IL-35 at present. The family members share many similar structures, but they have their own distinctive biological characteristics and play different roles to balance the functional effects of their own family. IL-12 and IL-23 are positive regulators and mainly play pro-inflammatory effect while IL-27 and IL-35 are negative regulators and mainly play anti-inflammatory effect. Thus, IL-12 family plays an important role in the regulation of the immune response and this function may be better than other cytokine family. IL-12 family has an important regulatory effect on multiple T cell subsets and also has an impact on their differentiation and function. So, we postulate that the IL-12 family may have an intense relationship with the generation and development of the allergic rhinitis. This article will mainly talk about the unique structure and role of the IL-12 cytokine family and discuss its immune regulation effect in the allergic rhinitis.

[External nose eccrine poroma：a case report].

Eccrine poroma is a benign neoplasm of the terminal duct. It is commonly located in distal extremities but rarely present in head and neck. This report mainly describes a case of external nose eccrine poroma. We will clarify the disease from pathology; histopathological examination; diagnosis; clinical manifestations to prognosis.

[Effects of specific immunotherapy on the expression levels of serum IL-17,IL-35 and Treg/Th17 regulatory T cellsin patients with allergic rhinitis caused by dermatophagoides].

Objective:To explore the regulatory effect of sublingual immunotherapy on the balance of Treg/Th17 cells and the expression of IL-17 and IL-35 in serum of allergic rhinitis(AR) in pre-specific and post-specific immunotherapy.Method:In this study,30 cases were randomly selected from outpatients of otolaryngological department in the second hospital of Hebei Medical university.These were attributed as pretherapy group.After treatment,the same patients were as renamed as the post-therapy group.Another 30 cases were healthy subjects enrolled from physical examination branch of our hospital.We detected the expression level of IL-35 and IL-17 in peripheral blood by using ELISA and defeced CD4⁺ CD25⁺ Foxp3⁺ T cell and CD4⁺ IL-17⁺ T cell expression level via flow cytometry.Result:The expression level of IL-17 in pre therapy group was obviously higher than that in control group(P<0.05);The expression level of IL-17 in post therapy group was obviously lower than that in pre-therapy group,The difference was a statistically significance(t=5.030,P<0.05);The expression level of IL-17 in post therapy group was also higher than that in control group(P <0.05 ).The expression level of IL-35 in pre-therapy group was obviously lower than that in control group(P<0.05);The expression level of IL-35 in post therapy was obviously higher than that in pre-therapy group;The difference was a statistically significance (t=-4.083,P<0.05),the expression level of IL-35 in post therapy group was also lower than that in control group(P<0.05).The percentage of CD4⁺CD25⁺Foxp3⁺ T cell in CD4⁺ T cell was significant lower in pre therapy group than that in control group (P<0.05);The percentage of CD4⁺CD25⁺Foxp3⁺ T cell in CD4+ T cell in post therapy was obviously higher than that in pre therapy group;The difference was a statistically significance(t=-10.584,P<0.05),The percentage of CD4⁺CD25⁺Foxp3⁺ T cell in CD4⁺ T cell was also lower in post therapy group than that in control group (P<0.05 ).The percentage of CD4⁺IL17⁺ T cell in CD4⁺ T cell was significant higher in pre therapy group than that in control group (P<0.05);The percentage of CD4⁺IL-17⁺ T cell in CD4⁺ T cell in post therapy group was obviously lower than that in pre therapy group.The difference was a statistically significance (t=6.258,P<0.05).The percentage of CD4⁺IL-17⁺ T cell in CD4⁺ T cell was also higher in post therapy group than that in control group (P<0.05 ).Conclusion:Specific immunotherapy can have an impact on the expression levels of IL-17,IL-35 and also on Treg/Th17 cells balance in peripheral blood for patients with allergic rhinitis.

Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics and pharmacodynamics of gliclazide in healthy Chinese Han volunteers.

BACKGROUND AND OBJECTIVE: CYP2C9 is the major contributor to gliclazide metabolic clearance in vitro, while the pharmacokinetics of gliclazide modified release are affected mainly by CYP2C19 genetic polymorphisms in vivo. This study aims to investigate the influence of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide in healthy Chinese Han volunteers. METHODS: Eighteen healthy Han subjects with various combinations of CYP2C9 and CYP2C19 genotypes received 80 mg gliclazide. Plasma gliclazide concentrations were measured by a liquid chromatography-tandem mass spectrometry method for 84 h and plasma glucose and insulin levels were measured up to 15 h post-dose. RESULTS AND DISCUSSION: There was no difference in either pharmacokinetic and or pharmacodynamic parameters of gliclazide when group A (CYP2C9*1/*1, CYP2C19 extensive metabolizers) was compared with group B (CYP2C9*1/*3, CYP2C19 *1/*1). When group C (CYP2C9*1/*1 and CYP2C19 poor metabolizers) was compared with group A, the AUC(0-∞) and C(max) in group C were significantly higher [83.94 ± 40.41 vs. 16.39 ± 5.10 µg·h/mL (P = 0.000) and 1.50 ± 0.85 vs. 0.45 ± 0.18 µg/mL (P = 0.000)], and the oral clearance was significantly lower [1.17 ± 0.63 vs. 5.38 ± 1.86 L/h (P = 0.000)]. The half-life of gliclazide was also significantly prolonged in group C subjects when compared with that of group A (33.47 ± 12.39 vs. 19.34 ± 10.45 h), but the difference was not significant (P = 0.052). The increase in serum glucose level at 11 h after dosing (ΔC(glu11)) in group C was significantly higher than that of group A (-1.08 ± 0.42 vs. 0.22 ± 1.01 mmol/L, P = 0.022). The corresponding insulin levels showed no difference between the two groups. CONCLUSION: CYP2C9*3 was not associated with any change in the disposition of gliclazide. CYP2C19 polymorphisms appear to exert the dominant influence on the pharmacokinetics of gliclazide in healthy Chinese Han subjects, and may also affect the observed pharmacodynamics of the drug as a result.

Kinetics and thermodynamics of adsorption of ionizable aromatic compounds from aqueous solutions by as-prepared and oxidized multiwalled carbon nanotubes.

The adsorption of 1-naphthylamine, 1-naphthol and phenol on as-prepared and oxidized multiwalled carbon nanotubes (MWCNTs) has been investigated. The results illustrated that both as-prepared and oxidized MWCNTs showed high adsorption capacity for the three ionizable aromatic compounds (IACs) studied. Oxidation of MWCNTs increased the surface area and the pore volume, and introduced oxygen-containing functional groups to the surfaces of MWCNTs, which depressed the adsorption of IACs on MWCNTs. Both Langmuir and Freundlich models described the adsorption isotherms very well and the adsorption thermodynamic parameters (DeltaG degrees, DeltaH degrees and DeltaS degrees) were measured. The adsorption for 1-naphthylamine, 1-naphthol and phenol is general spontaneous and thermodynamically favorable. The adsorption of phenol is an exothermic process, whereas the adsorption of 1-naphthylamine and 1-naphthol is an endothermic process. Results of this work are of great significance for the environmental application of MWCNTs for the removal of IACs from large volume of aqueous solutions.

Identification of nonlinear systems with unknown time delay based on time-delay neural networks.

In this letter, we address the problem of online identification of nonlinear continuous-time systems with unknown time delay based on neural networks (NNs). A novel time-delay NN model with learning algorithm is employed to perform simultaneous system identification and time-delay estimation. The proposed network is an extended version of the time-delay-free dynamical NN. Rigorous stability proof for the identification error is given by means of Lyapunov theory. The simulation studies are provided to demonstrate the performance of the identification algorithm and clarify the theoretical implications.

Quasi-one-dimensional molecular magnets based on derivatives of (fluorobenzyl)pyridinium with the [M(mnt)2] monoanion (M = Ni, Pd or Pt; mnt2- = maleonitriledithiolate): syntheses, crystal structures and magnetic properties.

The syntheses, structural characterizations and magnetic behaviors of three new complexes, 1-(3',4',5'-trifluorobenzyl)pyridinium [M(mnt)2]- [M = Ni (1), Pd (2) or Pt (3)], are reported. These complexes are isomorphous and their prominent structural character is that the [M(mnt)2]- anions form columnar stacks, in which the dimerization was observed. Complexes 2 and 3 are diamagnetic, while 1 possesses an energy gap of 2474 K. For crystal 4, 1-(4'-fluorobenzyl)pyridinium [Ni(mnt)2] (its structure and magnetic susceptibility were briefly reported earlier), the magnetic behavior can be divided into two regimes, namely, weakly ferromagnetic coupling above 93 K and strongly antiferromagnetic coupling below 93 K. A transition occurs at 93 K which switches the magnetic exchange nature from ferromagnetic to antiferromagnetic. A sharp thermal abnormality with lambda-shape, associated with the transition, appears from its heat capacity measurement to indicate that the transition is first order. The temperature dependences of the superlattice diffractions revealed the existence of the pretransitional phenomena up to at least 140 K. The unusual magnetic behavior of 4, such as the origin of the ferromagnetic interaction in the high temperature phase and what causes the spin transition, are discussed further.

Structural and magnetic investigations for the doping effect of nonmagnetic impurity on the spin-Peierls-like transition in a quasi-one-dimensional magnet: 1-(4'-nitrobenzyl)pyridinium bis(maleonitriledithiolato)nickelate.

A nonmagnetic compound, [NO(2)BzPy][Au(mnt)(2)] (NO(2)BzPy(+) = 1-(4'-nitrobenzyl)pyridinium; mnt(2-) = maleonitriledithiolate), was synthesized and characterized structurally, which is isostructural with [NO(2)BzPy][Ni(mnt)(2)] that is a quasi-one-dimensional magnet and possesses a spin-Peierls-like transition with J = 192 K in the gapless state and spin energy gap = 738 K in the dimerization state, respectively. Further, ten nonmagnetic impurity doped compounds with a formula [NO(2)BzPy][Au(x)Ni(1-x)(mnt)(2)] (x = 0.01-0.73) were prepared and investigated by crystal structural determinations and magnetic susceptibility measurements. The nonmagnetic doping causes the suppression of the spin transition with an average rate of 221(12) K/percentage of dopant concentration. From the plots of chi(m)-T, the transition collapse (the characteristic of the transition is the sudden drop of chi(m) upon cooling, and the disappearance of this characteristic is considered as the criterion for the transition collapse) is estimated at around x > 0.27. In heavier doped system x = 0.49, the spin gap vanishes and a gapless phase is achieved again.

Design of a magnetic bistability molecular system constructed by H-bonding and pi...pi-stacking interactions.

Crystal structures and magnetic properties were determined for two novel polymorphs of the complex [H2DABCO][Ni(mnt)2] [(H2DABCO)2+ = diprotonated 1,4-diazabicyclo[2.2.2]octane; mnt2- = maleonitriledithiolate]. For each polymorph, anions form a layered structure in which two kinds of dimers were observed. The adjacent anionic sheets are held together by cations via H-bonding interactions between protons of cations and CN groups of anions. Two polymorphs possess spin bistability; namely, upon cooling, a magnetic transition happens at around 120 K with about 1 K hysteresis on heating for the alpha phase and at 112 K with about 10 K hysteresis for the beta phase. Above the transition, the magnetic behaviors of two polymorphs can be approximately interpreted by a singlet-triplet model of an antiferromagnetically coupled S = 1/2 dimer, which is supported by the crystal structures and spin dimer analyses based on extended Hückel molecular orbital calculations.

Structural phase transition driven by spin-lattice interaction in a quasi-one-dimensional spin system of [1-(4'-iodobenzyl)pyridinium][Ni(mnt)2].

Crystal structures and magnetic properties were determined for two novel compounds, [1-(4'-iodobenzyl)pyridinium][M(mnt)2] (mnt2- = maleonitriledithiolate; M = Ni (1) or Cu (2)). At room temperature, single crystals of 1 and 2 were isostructural, featuring the formation of segregated columnar structures with regular stacks of cations and anions. For crystal 1, a magnetic transition was observed at approximately 120 K; furthermore, its magnetic behavior was consistent with that of a regular Heisenberg antiferromagnetic (AFM) chain of S = 1/2 in the high-temperature phase (HT phase) and that of a spin-gap system in the low-temperature phase (LT phase). Such a phenomenon is similar to the spin-Peierls transition. However, the crystal structure of 1 in the LT phase at 100 K revealed that its structural transition is associated with the magnetic transition. Because crystal 2 (S = 0) did not exhibit a structural transition, the structural transition of 1 is driven by spin-lattice interaction.

Ionic pair complexes with well-separated columnar stack structure based on [Pt(mnt)2]- ions showing unusual magnetic transition: syntheses, crystal structures, and magnetic properties.

Three ion pair complexes, [4-R-benzylpyridinium][bis(maleodinitriledithiolato)platinum(III)] (abbreviated as [RBzPy][Pt(mnt)(2)]; R = Cl (1), Br (2), or NO(2) (3)), have been synthesized. The cations and anions stack into well-separated columns in the solid state, and the Pt(III) ions form a 1-D zigzag chain within a [Pt(mnt)(2)](-) column through Pt...S, S...S, and Pt...S...Pt interactions. The chain is uniform in 1 and 2, while it alternates in 3. Unusual magnetic phase transitions from paramagnetism to diamagnetism were observed in these three complexes at approximately 275 K for 1, approximately 269 K for 2, and approximately 184 K for 3. These phase transitions were also found in DSC measurements for 1 and 2. The overall magnetic behaviors for 1-3 indicate the presence of antiferromagnetic exchange interactions in the high-temperature phase and spin-gapped systems in the low-temperature phase. Below 50 K, 2 exhibits weak ferromagnetism. The spontaneous moments are nearly repressed by a field of 1.0 T. The crystal structure of 2 at 173 K reveals that there are two crystallographically independent [Pt(mnt)(2)](-) entries in an asymmetric unit. These two crystallographically independent [Pt(mnt)(2)](-) entries satisfy the spin-canting condition, and the EPR spectra measured at room temperature exhibit anisotropic character. Therefore, the weak ferromagnetic behavior in the low-temperature region for 2 can be attributed to the spin-canting phenomenon.

2-Methyl-1-(4-nitrobenzyl)pyridinium bis(maleonitriledithiolato)nickelate(III).

In the title complex, 2-methyl-1-(4-nitrobenzyl)pyridinium bis(1,2-dicyanoethene-1,2-dithiolato)nickelate(III), (C(13)H(13)N(2)O(2))[Ni(C(4)N(2)S(2))(2)], the most prominent general structural feature of the complex is the completely segregated columnar stacks of anions and cations. Within the cation column, there may be stacking interactions between adjacent nitro groups and benzene rings.

The inclusion compound of a new ionizable derivative of beta-cyclodextrin with ferrocenium drug.

A new beta-cyclodextrin (beta-CD) derivative, mono[6-deoxy-6-(2-butenedinitrile-2,3-dimercapto sodium salt)]-beta-CD (6-mnt-beta-CD), and its inclusion compound with a ferrocenium drug, have been prepared and characterized by IR, UV, 13C-NMR spectroscopy, and mass spectrometry, elemental analysis, thermogravimetry, and cyclic voltammetry (CV). The interplay between the side-arm anion of beta-CD and the ferrocenium (guest) in the inclusion compound 6-mnt-beta-CD-/Fc+ has been investigated by 13C-NMR, UV, IR, and thermogravimetric methods. Charge transfer from the anion to the cation in 6-mnt-beta-CD-/Fc+ was then experimentally identified. The interaction between the guest and the host with side-arm in 6-mnt-beta-CD-/Fc+ resulted in smaller positive potential shifts compared to that in the inclusion compound [beta-CD/Fc+]BF4-.

Spectroscopic and theoretical studies on copper(II) complex of maleinitriledithiolate and 1,10-phenanthroline.

A complete vibrational spectra analysis of the title complex is performed in this paper. The molecular geometry, binding, electron structure and spectroscopic properties for the title complex are studied in detail by PM3 or ZINDO/S method. It has been found that this complex has a planar structure belonging to the symmetry point group C2v and its ground state is the spin doublet state. By comparison with the observed results, it can be concluded that PM3 methods are reliable to calculate the vibrational spectra of this molecule. It is worth noting that the scientific method of assigning vibrational spectra for a complicated molecule containing metal is established herein for the first time by giving main fixed points and pivotal vibrational units. Besides the regular symbols, the new defined symbols eta and M play an important role in describing the vibrational modes accurately and vividly.