Discovery of a novel inhibitor of nitric oxide production with potential therapeutic effect on acute inflammation.

Inflammation as a host's excessive immune response to stimulation, is involved in the development of numerous diseases. To discover novel anti-inflammatory agents and based on our previous synthetic work on marine natural product Chrysamide B, it and a series of derivatives were synthesized and evaluated for their anti-inflammatory activity on inhibition of LPS-induced NO production. Then the preliminary structure-activity relationships were conducted. Among them, Chrysamide B is the most potent anti-inflammatory agent with low cytotoxicity and strong inhibition on the production of NO (IC50 = 0.010 µM) and the activity of iNOS (IC50 = 0.082 µM) in LPS-stimulated RAW 264.7 cells. Primary studies suggested that the mechanism of action may be that it interfered the formation of active dimeric iNOS but not affected transcription and translation. Furthermore, its good performance of anti-inflammatory effect on LPS-induced multiple inflammatory cytokines production, carrageenan-induced paw edema, and endotoxin-induced septic mice, was observed. We believe that these findings would provide an idea for the further modification and research of these analogs in the future.

Double 1,4-addition of (thio)salicylamides/thiosalicylic acids with propiolate derivatives: a direct, general synthesis of diverse heterocyclic scaffolds.

A simple and practical ring-closure procedure to prepare a range of diverse heterocycles has been developed. In this transformation, a variety of substituted (thio)salicylamides and thiosalicylic acids undergo a double 1,4-addition reaction with propiolate derivatives in the presence of an inorganic base (K3PO4), as a result benzothiazinones, benzoxazinones and benzoxathiinones were prepared in good to excellent yields, respectively, even in gram scales. In addition, further transformation towards more complex structures and oxicam drug analogues has also been successfully carried out.

[Discussion on relevant theories of "Qi-Blood-Shen" and formula implication of Guan-Xin-Jing capsule].

In the field of traditional Chinese medicine（TCM）,the definition of "Shen" contains a broad concept and a narrow concept. Broad "Shen" is the dominator and administrator of human vital movement,while narrow "Shen" means spirit, consciousness, thinking and emotions of human. "Shen" originates from innate essence of parents, and survives on acquired essence of water and food as well as the nutrition of its metaplastic Qi-Blood-Body fluid. Qi-Blood,the most precious asset of human body, is a quite important section of one person and the central material basis of "Shen-Zhi". Coronary heart disease(CHD) is classified as thoracic obstruction category in TCM. However, in the progress of CHD, the mental factors and physical factors interplay each other. Thus, CHD is defined as a kind of psychosomatic disorder. So, the concept of psycho-cardiology generally corresponds to the cognition of TCM. Disorder of Qi and Blood, Qi deficiency and Blood stasis and lack of spirit and "Shen" preservation, are the main causes of coronary heart disease(CHD). Guan-Xin-Jing capsule possesses multiple therapeutical effects including supplementing qi and activating blood circulation, tranquilizing "Shen" and sedating "Zhi" and balancing psychosomatic status. It will be of vital importance and promotional value in the prophylaxis and treatment of CHD.

[Prescription rules of preparations containing Crataegi Fructus in Chinese patent drug].

To analyze the prescription rules of preparations containing Crataegi Fructus in the drug standards of the People's Republic of China Ministry of Public Health-Chinese Patent Drug(hereinafter referred to as Chinese patent drug), and provide some references for clinical application and the research and development of new medicines. Based on TCMISS(V2.5), the prescriptions containing Crataegi Fructus in Chinese patent drug were collected to build the database; association rules, frequency statistics and other data mining methods were used to analyze the disease syndrome, common drug compatibility and prescription rules. There were a total of 308 prescriptions containing Crataegi Fructus, involving 499 kinds of Chinese medicines, 34 commonly used drug combinations, and mainly for 18 kinds of diseases. Drug combination analysis was done with "Crataegi Fructus-Citri Reticulatae Pericarpium" and "Crataegi Fructus-Poria" as the high-frequency herb pairs and with "stagnation" and "diarrhea" as the high-frequency diseases. The results indicated that the Crataegi Fructus in different herb pairs had a roughly same function, and its therapy effect was different in different diseases. The prescriptions containing Crataegi Fructus in Chinese patent drug had the effect of digestion, and they were widely used in clinical application, often used together with spleen-strengthening medicines to achieve different treatment effects; the prescription rules reflected the prescription characteristics of Crataegi Fructus for different diseases, providing a basis for its clinically scientific application and the research and development of new medicines.

[Analysis of chemical constituents from Citrus aurantium by UHPLC-LTQ-Orbitrap-MS/MS].

In this study, a ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS/MS) method was developed to analyze the chemical components in Citrus aurantium. C. aurantium were extracted with 75% methanol, and we applied a Thermo Scientific BDS Hypersil C18 column (2.1 mm×150 mm, 2.4 µm) to UHPLC analysis with acetonitrile-water (containing 0.1% formic acid) in gradient as mobile phase. Elutes were then detected by ESI-LTQ-Orbitrap-MS/MS. A total of 27 components were identified, including fourteen flavonoids, seven coumarins, five limonoids and one alkaloid. This study showed an insight into the composition of C. aurantium, which could provide theoretical foundation for further study and utilization of the medicinal resources.

[Changes in lymphocyte subsets in infants with common lower respiratory tract infectious diseases].

OBJECTIVE: To investigate the changes and clinical significance of lymphocyte subsets in infants with bronchitis, bronchopneumonia, and bronchiolitis. METHODS: A total of 111 children with bronchitis, 418 children with bronchopneumonia, and 83 children with bronchiolitis were enrolled as disease groups, and 235 healthy children were enrolled as control group. Flow cytometry was applied to measure lymphocyte subsets. RESULTS: The bronchitis group had significantly lower numbers of T cells and CD3+CD8+ T cells than the control group (P<0.05). The bronchopneumonia group had significantly lower numbers of T cells and CD3+CD8+ T cells, a significantly higher number of T helper (Th) cells, and a significantly higher CD4/CD8 ratio than the control group, as well as a significantly higher number of Th cells than the bronchitis group. Compared with the children with mild bronchopneumonia, those with severe bronchopneumonia showed a reduction in T cells and an increase in B cells (P<0.05). The bronchiolitis group had a significantly higher number of Th cells, a significantly higher CD4/CD8 ratio, and a significantly lower number of CD3+CD8+ T cells than the control group (P<0.01). The disease groups showed a significantly higher number of B cells and a significantly lower number of natural killer cells than the control group (P<0.05). CONCLUSIONS: A low, disturbed cellular immune function and a high humoral immune function are involved in the development and progression of lower respiratory tract infectious diseases. The changes in immune function are related to the type and severity of diseases.

Asymmetric H2O-Nucleophilic Ring Opening of D-A Cyclopropanes: Catalyst Serves as a Source of Water.

The first catalytic enantioselective ring-opening reaction of donor-acceptor cyclopropanes with water is described. By employing Cy-TOX/Cu(II) as catalyst, the reaction performed very well over a broad range of substrates, leading to the ring-opening products in 70-96% yields with up to 95% ee under mild conditions. The current method provides a new approach to direct access to γ-substituted GBH derivatives very efficiently. Importantly, Cu(ClO4)2·6H2O proves to serve as both a Lewis acid and a source of water, which affords a fine system to controllably release water as a nucleophile in the asymmetric catalysis.

Asymmetric 1,2-perfluoroalkyl migration: easy access to enantioenriched α-hydroxy-α-perfluoroalkyl esters.

This study has led to the development of a novel, highly efficient, 1,2-perfluoro-alkyl/-aryl migration process in reactions of hydrate of 1-perfluoro-alkyl/-aryl-1,2-diketones with alcohols, which are promoted by a Zn(II)/bisoxazoline and form α-perfluoro-alkyl/-aryl-substituted α-hydroxy esters. With (-)-8-phenylmenthol as the alcohol, the corresponding menthol esters are generated in high yields with excellent levels of diastereoselectivity. The mechanistic studies show that the benzilic ester-type rearrangement reaction takes place via an unusual 1,2-migration of electron-deficient trifluoromethyl group rather than the phenyl group. The overall process serves as a novel, efficient, and simple approach for the synthesis of highly enantioenriched, biologically relevant α-hydroxy-α-perfluoroalkyl carboxylic acid derivatives.

[Identification of pearl powder using microscopic infrared reflectance spectroscopy].

Pearl is a precious ornament and traditional Chinese medicine, which application history in China is more than 2000 years. It is well known that the chemical ingredients of shell and pearl are very similar, which all of them including calcium carbonate and various amino acids. Generally, shell powders also can be used as medicine; however, its medicinal value is much lower than that of pearl powders. Due to the feature similarity between pearl powders and shell powders, the distinguishment of them by detecting chemical composition and morphology is very difficult. It should be noted that shell powders have been often posing as pearl powders in markets, which seriously infringes the interests of consumers. Identification of pearl powder was investigated by microscopic infrared reflectance spectroscopy, and pearl powder as well as shell powder was calcined at different temperatures for different time before infrared reflectance spectroscopy analysis. The experimental results indicated that when calcined at 400 °C for 30 minutes under atmospheric pressure, aragonite in pearl powder partly transformed into calcite, while aragonite in shell powder completely transformed into calcite. At the same time, the difference in phase transition between the pearl powders 'and shell powders can be easily detected by using the microscopic infrared reflectance spectroscopy. Therefore, based on the difference in their phase transition process, infrared reflectance spectroscopy can be used to identify phase transformation differences between pearl powder and shell powder. It's more meaningfully that the proposed infrared reflectance spec- troscopy method was also investigated for the applicability to other common counterfeits, such as oyster shell powders and abalone shell powders, and the results show that the method can be a simple, efficiently and accurately method for identification of pearl powder.

Water as an activator for palladium(II)-catalyzed olefin polymerization.

By a reasonable combination of the Wacker reaction and olefin polymerization processes, water proves to be an excellent activator for the palladium(II)-catalyzed polymerization of ethylene and it provides a safe, environmental-friendly and handy initiator for olefin polymerization. The activity of the olefin polymerization is comparable to reactions catalyzed by the corresponding alkylated cationic palladium complexes.

Awareness of Hospice Care Among Community-Dwelling Elderly Participants.

Background and Purpose: The main goal of hospice care is to improve the quality of life for people who are at the end-of-life phase. However, investigations on the awareness of hospice care among community-dwelling elderly participants are limited. This work aimed to reveal the awareness status of hospice care and explore the factors influencing the awareness rate among elderly participants. Methods: A questionnaire survey was conducted among individuals aged 60 years and above. Results: A total of 4,969 individuals aged 60 years and above were randomly selected from 48 primary medical institutions in Handan. The awareness rate of hospice care in the baseline survey was 19.3% (n = 959). All included individuals were divided into two groups in accordance with their awareness of hospice care. The awareness of hospice care among participants with low educational level, living alone, and afraid of talking about death was low (p < .05). Implications for Practice: The level of awareness of hospice care among community-dwelling elderly participants is low. The influencing factors included educational level, living status, and fear of talking about death. The community-dwelling elderly participants' awareness of hospice care must be improved. It is recommended that public medical education and training should be enhanced to improve knowledge and awareness of hospice care among community-dwelling elderly residents with low educational level, living alone, and afraid of talking about death.

[A multicenter study of coronary artery disease and its risk factors in rheumatoid arthritis in China].

OBJECTIVE: To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA). METHODS: Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed. RESULTS: In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD. CONCLUSION: The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.

[Survey of tumor necrosis factor inhibitors application in patients with rheumatoid arthritis in China].

OBJECTIVE: To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors. METHODS: A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application. RESULTS: In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000). CONCLUSION: About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.

[Sulphasalazine in patients with rheumatoid arthritis in China: a cross-sectional study].

OBJECTIVE: To investigate the medication status of rheumatoid arthritis (RA) patients and to analyze the clinical use of sulphasalazine (SSZ) and the adverse effect. METHODS: A total of 1 096 outpatients and inpatients diagnosed with RA were investigated in 21 hospitals all over China from July 2009 to December 2010, including gender, age of onset, clinical manifestations, as well as the clinical characteristics and medication status of 160 RA patients who received SSZ therapy. RESULTS: In the group of 160 patients who received SSZ, the male-to-female ratio was 1:7, The average age at onset was (46.1±15.0) years, while the average course was (9.9±7.8) years. The average dose of sulphasalazine was (1.87±0.52) g/d for a mean duration of (26.3± 14.6) months. Only 17% (27/160) of the patients received SSZ monotherapy. Methotrexate (63.1%), leflunomide (36.2%) and hydroxychloroquine (18.1%) were most commonly used combination drugs. And 36.2% (58/160) of the patients used the two-drug combination of methotrexate plus sulphasalazine .In this group, 41.9% (67/160) once used SSZ but withdrew for adverse events and other reasons, while 17.5% (28/160) withdrew for adverse events, of which the most common were gastrointestinal (8.8%), skin (3.8%) and liver toxicity (3.1%). CONCLUSION: Sulphaszlazine is not a common choice in the RA therapeutics in China, and the average dose of SSZ is lower than the standard dose of 2 to 3 g/d . The adverse events of SSZ are common; however, there are few severe adverse events or threat to life,SSZ is relatively safe in clinical practice.

Characterization of a novel serine protease inhibitor gene from a marine metagenome.

A novel serine protease inhibitor (serpin) gene designated as Spi1C was cloned via the sequenced-based screening of a metagenomic library from uncultured marine microorganisms. The gene had an open reading frame of 642 base pairs, and encoded a 214-amino acid polypeptide with a predicted molecular mass of about 28.7 kDa. The deduced amino acid sequence comparison and phylogenetic analysis indicated that Spi1C and some partial proteinase inhibitor I4 serpins were closely related. Functional characterization demonstrated that the recombinant Spi1C protein could inhibit a series of serine proteases. The Spi1C protein exhibited inhibitory activity against α-chymotrypsin and trypsin with K(i) values of around 1.79 × 10(-8) and 1.52 × 10(-8) M, respectively. No inhibition activity was exhibited against elastase. Using H-d-Phe-Pip-Arg-pNA as the chromogenic substrate, the optimum pH and temperature of the inhibition activity against trypsin were 7.0-8.0 and 25 °C, respectively. The identification of a novel serpin gene underscores the potential of marine metagenome screening for novel biomolecules.

Direct copolymerization of ethylene with protic comonomers enabled by multinuclear Ni catalysts.

Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.

An injectable, self-healing hydrogel system from oxidized pectin/chitosan/γ-Fe2O3.

Injectable hydrogels with self-healing ability present great potential for drug delivery. They could be facilely implanted in vivo and maintained structural and functional integrity till the hydrogel arriving at target sites. Herein, a series of injectable and self-healing composite hydrogel were developed as delivery vehicles for anti-cancer drug. The hydrogels were obtained with varying ratios of oxidized pectin/chitosan to nano γ-Fe2O3, which present excellent injectable, self-healing, magnetic, high biocompatible, and anti-cancer properties. The nano γ-Fe2O3 with particle size of about 0.25 µm loaded on the surface of hydrogel. Magnetic hysteresis loops of the hydrogel presented S-shape over the applied magnetics and the MS value was 4.86 emu/g. When pH dropped from 7.4 to 6.5 or temperature increased form 36 °C to 37 °C, the percentage increase in the swelling rate of OP4-400 reached to 35.89% and 25.13%, respectively. The composite hydrogels could continuously release water-soluble 5-FU for more than 12 h. In addition, the drug delivery systems indicated acceptable anti-cancer property though trace amounts of 5-FU were added in the hydrogel systems. The addition of γ-Fe2O3 could not only be beneficial to the targeting but also collectively enhance the anti-cancer property.

Sodium Iodide (NaI)-Catalyzed Cross-Coupling for C-S Bond Formation via Oxidative Dehydrogenation: Cheap, Direct Access to Unsymmetrical Aryl Sulfides.

A simple and practical NaI-catalyzed direct C-H sulfenylation of arenes has been developed under air. In this reaction, aryl sulfides were obtained in moderate to excellent yields with high regioselectivity from readily available aromatic compounds and aryl/alkyl thiols, even on gram scale. To demonstrate the practicability of this reaction, two bioactive compound skeletons were synthesized in good yields. This method can also be used to late-stage modification of curcumin.

Dietary intake and risk of rheumatoid arthritis-a cross section multicenter study.

Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self-administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student's t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518-0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981-0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867-0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA.

Combined effects of independent variables on yield and protein content of pectin extracted from sugar beet pulp by citric acid.

The extraction of pectin from sugar beet pulp by citric acid was carried out under different conditions using Box-Behnken design for four independent variables (pH, temperature, time and liquid to solid ratio). The yield of sugar beet pulp pectin ranged from 6.3% to 23.0%, and the content of protein from 1.5% to 4.5%. All independent variables significantly affected the yield, and all variables except liquid to solid ratio significantly affected the protein content. The yield increased as decreasing pH of extracting solution, extending time and advancing temperature, and an opposite relationship of effects between variables and content of protein was obtained. The chemical composition of collected samples was determined. Moreover, from the results of emulsifying properties study, the extracted pectin from sugar beet pulp could prepare steady oil-in-water emulsions. Therefore, it was inferred that the extraction conditions could influence yield and protein content, resulting in different emulsifying property.