Preventive Effects of Qingfei Yihuo Capsules () on Air Pollution Associated Exacerbation of Chronic Obstructive Pulmonary Disease: A Single-blind, Randomized, Controlled Trial.

OBJECTIVE: To investigate the efficacy of Qingfei Yihuo Capsules (, QYCs) in preventing the air pollution associated exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: This was a prospective, parallel, single-blind, randomized, placebo-controlled trial. Sixty patients with stable Group D COPD were randomly allocated to receive either oral QYCs (intervention group) or placebos (control group, 30 cases per group) for 15 days in the presumed high-incidence air pollution season and followed-up for 1 year. Both groups were given individualized Western medicine therapy according to the Global Initiative for Chronic Obstructive Lung Disease criteria as usual. Total and separate numbers of acute exacerbation (AE) associated with striking air pollution was the primary outcomes. Secondary outcomes included total numbers of deteriorating respiratory symptoms and separate numbers associated with striking air pollution, as well as scores of COPD Assessment Test (CAT) and modified Medical Research Council Scale (mMRC). RESULTS: All the 60 patients completed the study. There was no statistical significance in total numbers of AE between the two groups (P>0.05). Compared with the control group, a significant reduction in air-pollution associated numbers of deteriorated respiratory symptoms was observed in the intervention group (1.9-1.2 vs. 3.6-2.4, P<0.01). At the end of follow-up, there was no significant difference in CAT and mMRC scores between the two groups (P>0.05). Only 2 patients in the intervention group reported diarrhea and recovered after drug discontinuance. CONCLUSION: For patients with Group D COPD, oral QYCs in high-incidence season of air pollution can effectively mitigate respiratory symptoms associated with air pollution, although there was no evidence that it had a significant reductive effect on AEs. (Registered at Chinese Clinical Trial Registry, registration No. ChiCTR-IOR-17013827).

RgnBe3B3+: theoretical investigation of Be3B3+ and its rare gas capability.

A series of Be3B3+ and its rare gas (Rg) containing complexes RgnBe3B3+ (Rg = He-Rn, n = 1-6) have been predicted theoretically using the B3LYP, MP2, and CCSD(T) methods to explore structures, stability, charge distributions, and nature of bonding. Both Be3B3+ and RgBe3B3+ are the global minima on the potential energy surfaces. In the RgnBe3B3+ complexes, the dissociation energy drops with the increase in number of Rg. Natural bond orbital (NBO) and topological analysis of the electron density (AIM) show that the Rg-Be bonds for Kr-Rn have some covalent character. The Rg-Be bond is stabilized dominantly by the Rg → Be3B3+ σ-donation from the valence p orbital of Rg to the vacant valence LUMO orbital of Rgn-1Be3B3+. Besides, other two π-donations also play important roles in stabilizing the Rg-Be bonds.

OBCN isomerization and noble gas insertion compounds of identical valence electron number species: stability and bonding.

A series of new noble gas (Ng) insertion compounds of the general type XNgX, XNgY and XNgY+ has been theoretically studied using ab initio and DFT methods herein. We first studied the isomerization process of the OBCN compound, and then investigated the bonding properties and stability of the compounds formed by inserting Ng into the single bond of the three low energy isomers by high-level ab initio calculations. The OBNgCN compounds are thermochemically stable with respect to all dissociation channels except for the processes of releasing OBCN/OBNC and free Ng. Furthermore, the two dissociation processes OBNgCN → Ng + OBNC and OBNgNC → Ng + OBCN are kinetically prohibited by the relatively high free energy barrier ranging from 22.7 to 31.7 kcal mol-1 except for the OBKrCN and OBKrNC analogues. And the adaptive natural density partitioning (AdNDP) analysis indicated that chemical bonding in OBNgCN compounds is realized via a delocalized 3-center 2-electron (3c-2e) σ-bond in the B-Ng-C moiety and a totally delocalized 5-center 2-electron (5c-2e) σ-bond in the whole O-B-Ng-C-N. Natural bond orbital (NBO) theory, atoms-in-molecules (AIM) and energy decomposition analysis (EDA) based on the molecular wavefunction revealed that the B-Ng bond and Ng-C bond have some covalent character in OBNgCN. In addition, the calculation and detailed bonding analysis on a large number of neutral and monocationic compounds with identical valence electron numbers to OBNgCN demonstrate that the two bonds directly linked to the Ng atoms have covalent properties in neutral compounds, whereas Ng forms one typical covalent bond and one partial covalent and partial ionic bond with the neighboring atoms in the monocationic compounds.

Noble gas inserted compounds of borazine and its derivative B3N3R6: structures and bonding.

Quantum chemistry computations were performed at the MP2 and B3LYP levels of theory using the basis sets aug-cc-pVDZ and def2-TZVPPD to study the noble gas (Ng) compounds formed by insertion of a Ng atom (Kr, Xe, Rn) into the B-H/F and N-H/F bonds of inorganic benzene B3N3H6 and its fluorine derivative B3N3F6. The geometrical structures were optimized and vibrational analysis was carried out to demonstrate these structures being local minima on the potential energy surface. The thermodynamic properties of the formation process of Ng compounds were calculated. A series of theoretical methods based on the wavefunction analysis, including NBO, AIM and ELF methods and energy decomposition analysis, was used to investigate the bonding nature of the noble gas atoms and the properties of the Ng compounds. The N-Ng bond was found to be stronger than the B-Ng bond, but the B-Ng bond is of typical covalent character and σ-donation from the Ng atom to the ring B atom makes the predominant contribution towards stability of the B-Ng bond. NICS calculation shows that these Ng-containing compounds are of weak π-aromaticity.

Compounds with Rare Gas-Selenium/Tellurium Bonds: A Theoretical Investigation on FRgLF n and FRgLF n-1+ (Rg = Kr-Rn, L = Se and Te, n = 1, 3, and 5).

A new type of interesting insertion compounds FRgLF n (Rg = Kr-Rn, L = Se and Te, n = 1, 3 and 5) and ionic FRgLF n-1+ obtained through the insertion of a rare gas atom into the selenium fluorides and tellurium fluorides have been explored theoretically using MP2, CCSD(T), and PBE0 calculations. These predicted species were examined to present the optimized geometries, vibrational modes, molecular properties, thermodynamic and kinetic stabilities and bond nature. The optimized structures are without imaginary frequencies and metastable. In neutral FRgLF n, F-Rg bonds should be of ionic character with large dissociation energy ranging from 150-200 kcal mol-1 that could be best described by F-(RgLF n)+. Rg-L bonds have some covalent character with lower interaction energies within the range 25-40 kcal mol-1. In FRgL+ and FRgLF2+, the bonding nature of the F-Rg and Rg-L bonds are somewhat similar to that of the neutral compounds. In FRgLF4+, the F-Rg bond could be of partial covalent type but the Rg-L bond could be considered as an ionic bond.

Monocyclic aromatic compounds BnRgn(n-2)+ of boron and rare gases.

The monocyclic compounds (BRg)3+(D3h), (BRg)42+(D4h), (BRg)53+(D5h) and (BRg)64+(D6h) formed between boron and rare gases Rg (He-Rn) are theoretically predicted to be stable structures and have π-aromaticity with a delocalized nc-2e π-system. For heavier rare gases Ar-Rn, the B-Rg bond energy is quite high and ranges from 15 to 96 kcal mol-1, increasing with the ring size and the atomic number of rare gases; the B-Rg bond length is close to the sum of covalent radii of B and Rg atoms; NBO and AIM analyses show that the B-Rg bonds for Ar-Rn have a typical covalent character. The B-Rg bond is stabilized mainly by σ-donation from the valence p orbital of Rg to the vacant valence orbital of the boron ring. We searched for a large number of isomers for the systems of Ar and found that the titled monocyclic compounds (BAr)3+(D3h), (BAr)42+(D4h) and (BAr)53+(D5h) should be global energy minima. For (BAr)64+ the global energy minimum is an octahedral caged structure, but the titled monocyclic compound is the secondary stable local energy minimum. The energy and thermodynamic stability of the ring BnRgn(n-2)+ cations indicate that these rare gas compounds may be viable species in experiments.

Substituent effects on the properties of the hemi-bonded complexes (XH2P···NH2Y)(+) (X, Y=H, F, Cl, Br, NH2, CH3, OH).

Ab initio calculations have been performed to study the structures, binding energies, and bonding properties of the hemi-bonded binary complexes (XH2P···NH2Y)(+) with the substituents X and Y being H, F, Cl, Br, NH2, CH3, and OH. The P···N interactions in these open-shelled systems have typical pnicogen bond characteristics but much stronger than the usual pnicogen bonds in closed-shell systems. This P···N bond can be strengthened by an electron-withdrawing substituent X or an electron-donating substituent Y, the bonding energy varies from 17 kcal mol(-1) of (CH3H2P···NH2F)(+) to 54 kcal mol(-1) of (FH2P···NH2CH3)(+). A nearly linear X-P···N arrangement is required by the pnicogen bond P···N and results in a strong hyperconjugation and charge transfer from the N lone pair to the X-P σ* antibond orbital for α spin, the P···N interaction is described as a single-electron σ bond of ß spin. The AIM and NBO analyses revealed that the P···N bonds in the majority of the hemi-bonded complexes are partly covalent in nature. Graphical Abstract The P···N interactions in the open-shelled systems (XH2P···NH2Y)(+) (X, Y=H, F, Cl, Br, NH2, CH3, OH) with bonding energy of 17~54 kcal mol(-1) have typical pnicogen bond characteristics but much stronger than the usual pnicogen bonds in closed-shell systems. This P···N bond can be strengthened by an electron-withdrawing substituent X or an electron-donating substituent Y.

Theoretical Predictions of C3v Symmetric Three-H-Bridged Noble Gas Compounds NgBeH3BeR, NgBeH3BR(+), and NgBH3BR(2).

A new series of stable noble gas-Lewis acid compounds NgBeH3BeR, NgBeH3BR(+), and NgBH3BR(2+) (R = F, H, CH3, Ng = He-Rn) with three 3c-2e H-bridged bonds have been predicted by use of the PBE0 and MP2 methods. The Ng-Be/B bonds are strong and have large binding energies 35-130, 9-38, and 4-13 kcal/mol for the doubly charged cations, singly charged cations, and neutral molecules, respectively. The binding energy and strength of the Ng-Be/B bonds increase largely from He to Rn but are insensitive to electronegativity of the substituent R. The Ng-B bonds in NgBH3BR(2+) should be typical covalent bonds and the Ng-Be bonds in NgBeH3BR(+) for heavy Ng atoms Kr, Xe, and Rn have some covalent character. The three bridging-H atoms have characteristic infrared vibrational modes with large IR intensity to be detected in spectroscopy experiments.

Role of NOD2 in regulating the immune response to Aspergillus fumigatus.

BACKGROUND: The nucleotide-binding oligomerization domain-2 (NOD2) is a type of intracellular receptor recognizing the cell wall molecules of bacteria and inducing the innate immune response. Its role in defense against fungal infection remains uncertain. We thus investigated the role of the NOD2/RIP2 pathway in host responses to Aspergillus fumigatus (Af) in RAW264.7 cells. METHODS: RAW264.7 cells were cultured and Af conidia were added to stimulate the cells. The dynamic mRNA and protein expressions of NOD2 and RIP2 kinase were examined by real-time PCR and Western blotting. The protein expressions of nuclear factor-kappaB (NF-κB) and pro-inflammatory tumor necrosis factor-alpha and interleukin-8 were also investigated. Specific siRNA for NOD2 was synthesized and used to confirm the effect of NOD2 in the immune response to Af conidia. RESULTS: The stimulation of the cell line by Af conidia resulted in a significantly increased expression of NOD2 protein and RIP2 kinase. The production of NF-κB and downstream cytokines were also increased simultaneously. On knockdown of the NOD2 using RNA interference, the activation of NF-κB was interrupted and the production of cytokines was reduced in the cell line stimulated by Af conidia. CONCLUSION: These results suggested that Af conidia induced NF-κB activation in a NOD2-dependent manner, which potentially contributed to the innate immune response.

[A study of pulmonary inflammatory reaction induced by N-protein of SARS-CoV in rat models and effects of glucocorticoids on it].

OBJECTIVE: To study the pulmonary inflammatory reaction induced by N-protein of SARS-CoV in rat models and the effects of glucocorticoids on the inflammatory reaction. METHODS: The pulmonary inflammatory reaction in rat models were induced by intratracheal instillation of N-protein of SARS-CoV with a dose of 0.2 mg/kg. The rats were randomly divided into four groups: normal saline control group (Nc group), N-protein group 1 (P1 group, 6 h), N-protein group 2 (P2 group, 24 h), and N-protein + dexamethasone group (P + D group, dexamethasone 10 mg/kg intraperitoneally). The blood samples, bronchial alveolar lavage fluid (BALF) and lung tissue were collected after challenge. The cytological and histopathologic changes of lung tissues were observed and the wet/dry ratios (W/D) of lung tissue were determined. The interleukin (IL)-6, IL-10 and transforming growth factor-beta1 (TGF-beta1) of serum and BALF were measured by ELISA. RESULTS: (1) Compared with the percentage of peripheral blood lymphocytes in Nc group [(68.42 +/- 13.07)%], that in P2 group [(50.50 +/- 14.36)%] was significantly decreased (P < 0.05); compared with Nc group and P2 group, that in P + D group was furthermore significantly decreased (P < 0.01). Compared with the total WBC of peripheral blood in Nc group [(5.86 +/- 2.25) x 10(9)] and P2 group [(4.83 +/- 1.49) x 10(9)], that in P + D group [(1.96 +/- 1.30) x 10(9)] was significantly decreased (P < 0.01). (2) Compared with the total WBC of BALF in Nc group [(95 +/- 29) x 10(7)], that in P2 group [(160 +/- 60) x 10(7)] was significantly increased (P < 0.05); but compared with P2 group, that in P + D group [(62 +/- 23) x 10(7)] was significantly decreased (P < 0.05). Analysis of BALF differential cell counts showed that the majority of cells were alveolar macrophages in all groups. (3) The W/D ratios of lung tissue in both P1 and P2 group [(5.18 +/- 0.29) and (5.19 +/- 0.34), respectively] after N-protein challenge were significantly increased than that in Nc groups [(4.77 +/- 0.27), P < 0.05]; the W/D ratio in P + D group (4.70 +/- 0.18) was significantly decreased than that in P2 group (P < 0.01). (4) Compared with Nc group, the levels of IL-6, IL-10, TGF-beta1 in both serum and BALF of P1 group were significantly increased (P < 0.01), and the levels of these cytokines in P2 group were significantly higher than those in P1 group (P < 0.01), but significantly lower in P + D group compared with P2 group (P < 0.01). CONCLUSIONS: The N-protein of SARS-CoV had pathogenicity and could induce obvious pulmonary inflammatory reaction and acute lung injury, which were related to the increase and imbalance of pro-inflammatory and anti-inflammatory cytokines. Glucocorticoids could effectively alleviate the pulmonary inflammatory reaction induced by N-protein of SARS-CoV.

[The effect of antioxidant treatment in pneumonia of granulocytopenic rats].

OBJECTIVE: To evaluate the therapeutic role of antioxidant intervention in granulocytopenia rats with pseudomonas aeruginosa pneumonia. METHODS: 90 male Sprague-Dawley rats were randomly divided into two groups. Group A: the control granulocytopenia group, in which the granulocytopenia was induced by using cyclophosphamide and cortisone acetate. Group B: the antioxidant intervention group, in which the granulocytopenia model was the same as group A, while peritoneal injection of NAC 150 mg.kg(-1).d(-1) half an hour after the immunocompromised model was reproduced, and the injection was continued for a consecutive 7 days, and NAC was injected once more half an hour before bacterial tracheal inoculation. The model of pulmonary infection was established by using standard a strain of pseudomonas aeruginosa. The time-course of the following was observed 0 h before bacterial inoculation, and 6 h, 9 h, 24 h, 48 h and 72 h after infection: the peripheral white blood cells, mortality, oxidant/antioxidant indexes, bacterial burden of lung tissue homogenate, pulmonary vascular permeability and lung wet/dry weight ratio, and the pulmonary histopathological changes. RESULTS: The peripheral white blood cells of both groups were less than 4 x 10(9)/L. The concentration of superoxide dismutase in both serum and lung tissue in group B were higher than that in group A, while concentration of malondialdehyde in group B was lower than that in group A. Pulmonary vascular permeability and lung wet/dry ratio of group B were much lower than that of group A. There was no difference in bacterial burden of lung tissue between the two groups. Group B showed a lower mortality than group A (16.3% vs 23.4%). Lung histopathological observation showed that lung injury, pulmonary congestion and hemorrhage were more serious or obvious in group A as compared with group B. Apoptotic bodies were found in the lung epithelial cells of Group A. CONCLUSIONS: Antioxidant intervention can alleviate lung injury in the granulocytopenia rats with pseudomonas aeruginosa pneumonia. It may become an important subsidiary approach to pneumonia in granulocytopenia patients.