[Risk assessment, safe medication and scientific supervision of traditional Chinese medicine containing aristolochic acids--toxicity is different among aristolochic acids, and detection and control of aristolochic acid â /â ¡ is critical].

The safety problem of traditional Chinese medicine containing aristolochic acid is of great concern in China and abraod, which poses a challenge in clinical application and supervision. There are many types of aristolochic acid analogues(AAAs) and 178 have been reported. According to the structure, they are classified into aristolochic acids(AAs) and aristololactams(ALs). The toxi-city is remarkably different among AAAs of different types. For example, AA-Ⅰ has strong nephrotoxicity and carcinogenicity, and the toxicity of AA-Ⅱ is lower than that of AA-Ⅰ. Besides, AA-Ⅳa and AA-Ⅰa are considered to have no obvious nephrotoxicity and carcinogenicity. The types and content of AAAs are significantly different among traditional Chinese medicines derived from different Aristolochiaceae species. For example, Asari Radix et Rhizoma and Aristolochiae Herba mainly consist of AAAs without obvious toxicity(such as AA-Ⅳa). The content of AAAs in compound preparations is related to the proportions of the medicinals and the processing method. The content of AA-Ⅰ in some compound preparations is very low or below the detection limit. Therefore, the author concludes that AAAs of different types have different toxicity, but not all AAAs has nephrotoxicity and carcinogenicity. Moreover, the toxicity of traditional Chinese medicines containing AAAs should not be generalized and AA-Ⅰ and AA-Ⅱ should be emphasized. In this paper, it is suggested that traditional Chinese medicine containing AAAs should be used rationally and research, analysis, and toxicological study of AAAs species and content should be strengthened. In addition, limit standards of AA-Ⅰ and AA-Ⅱ should be formulated and science-based supervision should be performed.

[A novel mouse allergy tested model and its application for traditional Chinese medicine injections's allergy evaluation].

When the drug induces the organism to produce a type Ⅰ allergic reaction, the combination of IgE and mast cells results in the degranulation of the mast cells. Release of vasoactive substances, increase in vascular permeability, and exudation of intravascular substances outside the blood vessels. Based on this pathophysiological mechanism, a mouse model that can objectively and quantitatively assess the allergic response to the injection has been established. ICR mice were sensitised by intraperitoneal injection of different doses of OVA once every two days for three times. 14 days after the last sensitization, a combination OVA solution of 4 times the sensitizing dose and Evans blue were injected intravenously into mice for the challenge. Compared with the normal group, OVA 0.625/2.5, 1.25/5, 2.5/10, 5/20 mg·kg~(-1) sensitized and challenged can induce allergic reactions mainly manifested by blue staining of the auricle in mice. Direct injection of OVA intravenously did not cause an auricular blue colouration reaction in mice. The passive cutaneous anaphylaxis reaction in mice was conducted with the aforementioned OVA-sensitized mouse serum, and there were obvious blue spots on the mouse's back. In addition, the content of anti-OVA-IgE in 5 mg·kg~(-1) OVA-sensitized mice was significantly increased. Ears and lungs of mice sensitized to OVA showed evident exudation inflammation. Significantly elevated inflammatory factors(VEGF and IL-10) were also detected in the serum of OVA-sensitized mice. The equivalent dose of OVA caused obvious allergic reactions in both guinea pigs and mice. Compared with nude mice, ICR and BALB/c mice are more sensitive to OVA sensitization. Injections of selected TCMI did not induce type Ⅰ allergic reactions in mice and guinea pigs, but there was a risk of inducing pseu-doallergic reactions in mice. The model is problematic and may well reflect the sensitization effect of allergens. It obtains the benefits of simple operation, accuracy, low cost, easy extension, and high repeatability. It is suitable for predicting and researching for IgE-dependent type Ⅰ allergic reactions.

Precise Orbit Determination of MEX Flyby Phobos Using Simulated Radiometric and Image Data.

A navigation camera or topography camera is a standard payload for deep space missions and the image data are normally used for auto-navigation. In this work, we study the potential contribution of image data in precise orbit determination for deep space spacecraft. The Mars Express (MEX) spacecraft has generated extensive Phobos image data during flybys of Phobos, but these data have not been used in precise orbit determination because of the difficulty in employing these image data. Therefore, we did an experiment using simulated image data as the first step for exploring how to use real image data in precise orbit determination of spacecraft. Our results demonstrate that image data can provide stronger constraints on orbit in the tangential and normal directions than Doppler data. When the image data were used in the MEX orbit determination during the MEX Phobos flyby, the orbit determination accuracies in the tangential and normal directions were significantly improved. This work will provide a reference for real image data processing during MEX Phobos flyby to improve MEX orbit accuracy as well as Phobos ephemeris accuracy.

A matrix dispersion based on phospholipid complex system: preparation, lymphatic transport, and pharmacokinetics.

Raloxifene hydrochloride (RH) suffers from low oral bioavailability due to its low water-solubility and first-pass metabolism. Therefore, a novel phospholipid complex of RH (RHPC) and a matrix dispersion based on phospholipid complex (RHPC-MD) were successfully prepared and optimized. Several methods were used to validate the formation of RHPC and RHPC-MD, such as differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, infrared spectroscopy, particle size, and zeta potential, meanwhile, their octanol-water partition coefficient, solubility, and dissolution in vitro were also evaluated. To investigate the absorption mechanism of RHPC in vivo, the RHPC was administered to the chylomicron flow blockage rat model. Interestingly, as we expected, a significant reduction in RHPC absorption (67%) (**p< .01) in presence of cycloheximide (CXI) inhibitor was observed, thus confirming the RHPC could be absorbed by lymphatic transport in vivo. Pharmacokinetic studies revealed that the relative oral bioavailability of RHPC as well as RHPC-MD was 223% and 329%, respectively, when comparing with the commercial RH tablets. These outcomes suggested that the current study provided an attractive formulation to enhance the oral bioavailability of RH and stimulated to further research the absorption mechanism of RHPC in vivo.

Shuxuening injection, derived from Ginkgo biloba leaf, induced pseudo-allergic reactions through hyperactivation of mTOR.

Context: Shuxuening injection (SXNI), derived from the leaf of Ginkgo biloba L. (Ginkgoaceae), is widely used to treat cardio-cerebral vascular system related disease due to the efficacy of dilating the blood vessels and improving the function of microcirculation. Nevertheless, SXNI induces immediate hypersensitivity reactions in clinics and the molecular mechanisms are unknown.Objective: The present study investigates the molecular mechanism of SXNI mediated hypersensitivity reactions.Materials and methods: Naive male ICR mice (n = 10) were administered (i.v.) with negative control combined with Evans blue (EB) (CTL-EB), SXNI (14 or 70 mg/kg) combined with EB (SXNI/1-EB or SXNI/4-EB), vascular leakage was evaluated, ears and lungs were collected for histopathological analysis. In vitro, TSC1 was knockdown in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with SXNI, and the alterations of endothelial cell permeability were observed. Rapamycin (mTOR inbibitor) was used to investigate SXNI-induced hypersensitivity reactions both in mice and HUVECs.Results: SXNI (70 mg/kg) induced vascular leakage in mice. Slight oedema and microvascular dilation in the ears, and broaden of alveolar septal and monocyte infiltration in the lungs were observed in SXNI (70 mg/kg) treated mice. mTOR inhibitor alleviates SXNI mediated vascular endothelial hyperpermeability both in vitro and in vivo.Discussion and conclusions: SXNI stimulates pseudo-allergic reactions through hyperactivation of mTOR signalling pathway. Our work provides the new molecular mechanism of drug related pseudo-allergic reactions, and a potential drug to prevent and treat SXNI mediated hypersensitivity reactions.

Genome-wide transcriptional analysis of Aristolochia manshuriensis induced gastric carcinoma.

Context: Aristolochia manshuriensis Kom (Aristolochiaceae) (AMK) is known for toxicity and mutagenicity.Objective: The tumorigenic role of AMK has yet to be understood.Materials and methods: AMK extracts were extracted from root crude drug. SD (Sprague Dawley) rats underwent gavage with AMK (0.92 g/kg) every other day for 10 (AMK-10) or 20 (AMK-20) weeks. Stomach samples were gathered for histopathological evaluation, microarray and mRNA analysis.Results: The gastric weight to body weight ratio (GW/BW) is 1.7 in the AMK-10 cohort, and 1.8 in AMK-20 cohort compared to control (CTL) cohort. Liver function was damaged in AMK-10 and AMK-20 rats compared to CTL rats. There were no significant changes of CRE (creatinine) in AMK-10 and AMK-20 rats. Histopathological analysis revealed that rats developed dysplasia in the forestomach in AMK-10 rats, and became gastric carcinoma in AMK-20 rats. Genes including Mapk13, Nme1, Gsta4, Gstm1, Jun, Mgst2, Ggt6, Gpx2, Gpx8, Calml3, Rasgrp2, Cd44, Gsr, Dgkb, Rras, and Amt were found to be critical in AMK-10 and AMK-20 rats. Pik3cb, Plcb3, Tp53, Hras, Myc, Src, Akt1, Gnai3, and Fgfr3 worked in AMK-10 rats, and PDE2a and PDE3a played a pivotal role in AMK-20 rats.Discussion and conclusions: AMK induced benign or malignant gastric tumours depends on the period of AMK administration. Genes including Mapk13, Nme1, Gsta4, Gstm1, Jun, Mgst2, Ggt6, Gpx2, Gpx8, Calml3, Rasgrp2, Cd44, Gsr, Dgkb, Rras, Amt, Pik3cb, Plcb3, Tp53, Hras, Myc, Src, Akt1, Gnai3, Fgfr3, PDE2a, and PDE3a were found to be critical in aristolochic acid-induced gastric tumour process.

Propofol Sedation Alters Perceptual and Cognitive Functions in Healthy Volunteers as Revealed by Functional Magnetic Resonance Imaging.

BACKGROUND: Elucidating networks underlying conscious perception is important to understanding the mechanisms of anesthesia and consciousness. Previous studies have observed changes associated with loss of consciousness primarily using resting paradigms. The authors focused on the effects of sedation on specific cognitive systems using task-based functional magnetic resonance imaging. The authors hypothesized deepening sedation would degrade semantic more than perceptual discrimination. METHODS: Discrimination of pure tones and familiar names were studied in 13 volunteers during wakefulness and propofol sedation targeted to light and deep sedation. Contrasts highlighted specific cognitive systems: auditory/motor (tones vs. fixation), phonology (unfamiliar names vs. tones), and semantics (familiar vs. unfamiliar names), and were performed across sedation conditions, followed by region of interest analysis on representative regions. RESULTS: During light sedation, the spatial extent of auditory/motor activation was similar, becoming restricted to the superior temporal gyrus during deep sedation. Region of interest analysis revealed significant activation in the superior temporal gyrus during light (t [17] = 9.71, P < 0.001) and deep sedation (t [19] = 3.73, P = 0.001). Spatial extent of the phonologic contrast decreased progressively with sedation, with significant activation in the inferior frontal gyrus maintained during light sedation (t [35] = 5.17, P < 0.001), which didn't meet criteria for significance in deep sedation (t [38] = 2.57, P = 0.014). The semantic contrast showed a similar pattern, with activation in the angular gyrus during light sedation (t [16] = 4.76, P = 0.002), which disappeared in deep sedation (t [18] = 0.35, P = 0.731). CONCLUSIONS: Results illustrate broad impairment in cognitive cortex during sedation, with activation in primary sensory cortex beyond loss of consciousness. These results agree with clinical experience: a dose-dependent reduction of higher cognitive functions during light sedation, despite partial preservation of sensory processes through deep sedation.

Forsythoside A and Forsythoside B Contribute to Shuanghuanglian Injection-Induced Pseudoallergic Reactions through the RhoA/ROCK Signaling Pathway.

In recent years, hypersensitivity reactions to the Shuanghuanglian injection have attracted broad attention. However, the componential chief culprits inducing the reactions and the underlying mechanisms involved have not been completely defined. In this study, we used a combination of approaches based on the mouse model, human umbilical vein endothelial cell monolayer, real-time cellular monitoring, immunoblot analysis, pharmacological inhibition, and molecular docking. We demonstrated that forsythoside A and forsythoside B contributed to Shuanghuanglian injection-induced pseudoallergic reactions through activation of the RhoA/ROCK signaling pathway. Forsythoside A and forsythoside B could trigger dose-dependent vascular leakage in mice. Moreover, forsythoside A and forsythoside B slightly elicited mast cell degranulation. Correspondingly, treatment with forsythoside A and forsythoside B disrupted the endothelial barrier and augmented the expression of GTP-RhoA, p-MYPT1, and p-MLC2 in a concentration-dependent manner. Additionally, the ROCK inhibitor effectively alleviated forsythoside A/forsythoside B-induced hyperpermeability in both the endothelial cells and mice. Similar responses were not observed in the forsythoside E-treated animals and cells. These differences may be related to the potential of the tested compounds to react with RhoA-GTPγS and form stable interactions. This study innovatively revealed that some forsythosides may cause vascular leakage, and therefore, limiting their contents in injections should be considered.

The Involvement of the RhoA/ROCK Signaling Pathway in Hypersensitivity Reactions Induced by Paclitaxel Injection.

A high incidence of hypersensitivity reactions (HSRs) largely limits the use of paclitaxel injection. Currently, these reactions are considered to be mediated by histamine release and complement activation. However, the evidence is insufficient and the molecular mechanism involved in paclitaxel injection-induced HSRs is still incompletely understood. In this study, a mice model mimicking vascular hyperpermeability was applied. The vascular leakage induced merely by excipients (polyoxyl 35 castor oil) was equivalent to the reactions evoked by paclitaxel injection under the same conditions. Treatment with paclitaxel injection could cause rapid histamine release. The vascular exudation was dramatically inhibited by pretreatment with a histamine antagonist. No significant change in paclitaxel injection-induced HSRs was observed in complement-deficient and complement-depleted mice. The RhoA/ROCK signaling pathway was activated by paclitaxel injection. Moreover, the ROCK inhibitor showed a protective effect on vascular leakage in the ears and on inflammation in the lungs. In conclusion, this study provided a suitable mice model for investigating the HSRs characterized by vascular hyperpermeability and confirmed the main sensitization of excipients in paclitaxel injection. Histamine release and RhoA/ROCK pathway activation, rather than complement activation, played an important role in paclitaxel injection-induced HSRs. Furthermore, the ROCK inhibitor may provide a potential preventive approach for paclitaxel injection side effects.

Binding of Organometallic Ruthenium Anticancer Complexes to DNA: Thermodynamic Base and Sequence Selectivity.

Organometallic ruthenium(II) complexes [(η6-arene)Ru(en)Cl][PF6] (arene = benzene (1), p-cymene (2), indane (3), and biphenyl (4); en = ethylenediamine) are promising anticancer drug candidates both in vitro and in vivo. In this paper, the interactions between ruthenium(II) complexes and 15-mer single- and double-stranded oligodeoxynucleotides (ODNs) were thermodynamically investigated using high performance liquid chromatography (HPLC) and electrospray ionization mass spectroscopy (ESI-MS). All of the complexes bind preferentially to G8 on the single strand 5'-CTCTCTT7G8T9CTTCTC-3' (I), with complex 4 containing the most hydrophobic ligand as the most reactive one. To the analogs of I (changing T7 and/or T9 to A and/or C), complex 4 shows a decreasing affinity to the G8 site in the following order: -AG8T- (K: 5.74 × 104 M-1) > -CG8C- > -TG8A- > -AG8A- > -AG8C- > -TG8T- (I) ≈ -CG8A- (K: 2.81 × 104 M-1). In the complementary strand of I, the G bases in the middle region are favored for ruthenation over guanine (G) bases in the end of oligodeoxynucleotides (ODNs). These results indicate that both the flanking bases (or base sequences) and the arene ligands play important roles in determining the binding preference, and the base- and sequence-selectivity, of ruthenium complex in binding to the ODNs.

[Preclinical study on adverse reactions of Xingnaojing injection].

In this study, different batches of Xingnaojing injection products were first selected for pseudoallergic mice test, and the results showed that after injection of 6.6-fold clinical dose Xingnaojing injection, the mice showed a slight pseudoallergic reaction, while other mice injected with other batches of injections showed no obvious pseudoallergic reaction. Therefore, it is preliminarily believed that this mice model can effectively indicate the risk of pseudoallergic reactions in the clinical application of Xingnaojing injections. In addition, by changing some of the processes, a high concentration of Xingnaojing injection was prepared for mice pseudoallergic test and guinea pig systemic allergy test. The results showed no significant type Ⅰ allergic reaction in guinea pigs. Mild pseudoallergic reactions occurred in mice after a 6.6-fold clinical dose injection. Therefore, it is considered that for sensitive or idiosyncratic people, the concentration of certain chemical components in Xingnaojing injection will increase after entering the body, which may increase the risk of pseudoallergic reaction. However, due to the limitations of test models, the risk of Xingnaojing injection to induce allergic reactions cannot be ruled out. Finally, by increasing the content of borneol and Tween and (or) sodium chloride in Xingnnaojing Injection and testing its pseudoallergic reactions, the results showed that the combination of these three ingredients may produce new trace sensitization substance and induce pseudoallergic reactions.

[Pharmacokinetic characteristics of fourteen main components of Gegen Qinlian Decoction in rats].

Animal traditional Chinese medicine has a long history of application in China, and its clinical application is very extensive. Due to the complex chemical composition in animal traditional Chinese medicine, the basis of chemical research is relatively weak, which leads to the unclear composition and toxic components of many animal Chinese medicines. The relationship between the medicinal and toxic components of animal Chinese medicine has not yet been elucidated. The non-clinical safety evaluation of animal traditional Chinese medicine mainly includes acute toxicity, long-term toxicity, safety pharmacology, reproductive toxicity, genotoxicity experiments, and experimental studies such as carcinogenicity are needed when necessary. The current preclinical safety research on animal traditional Chinese medicine is mainly based on the study for toxic animal traditional Chinese medicines. Most animal Chinese medicines have not carried out systematic preclinical and clinical safety studies. The research method is mainly focused on acute toxicity test. It is necessary to carry out systematic preclinical safety studies on animal traditional Chinese medicines, to clarify the possible side effects and its characteristics, its toxic target organs, toxic doses and poisoning mechanisms induced by different animal traditional Chinese medicines. Finally, this paper suggests that in the preclinical safety study of animal traditional Chinese medicine, in-depth research and comparison should be carried out in combination with chemical substance foundation, origin, and collection season, and the safety of "non-toxic" animal traditional Chinese medicine should be carried out when necessary. In addition, it is necessary to rationally use the cutting-edge technologies and methods of toxicology research to fully clarify the preclinical safety information of animal Chinese medicines.

[Pseudoallergic reaction characteristics of Qingkailing injection and preliminary screening of allergic substances].

This study aimed to explore the characteristics and the influencing factors of Qingkailing injection (QKLI) pseudoallergic reaction, and screen out the possible pseudoallergenic substances. The results showed that ICR and Kunming mice had stronger pseudoallergic reactions than BALB/c and C57 mice after being injected with the same dose of QKLI. The pseudoallergic reaction induced by QKLI that was prepared with 0.9% saline was stronger than that prepared with 5% glucose. When the dose was twice of the clinical dose, some batches of QKLI could cause significant or suspected pseudoallergic reactions; when the dose dropped to clinically equal times, all of the batches did not induce pseudoallergic reactions in mice. Different batches of QKLI induced different pseudoallergic reactions in mice. Therefore, QKLI's pseudoallergic reactions might have a certain relationship with different body constitutions. Different solvents might affect the safety of QKLI. QKIL-induced pseudoallergic reactions had the different characteristics between batches, and the dosage should be strictly controlled in clinical use. After the comparison of pseudoallergic reactions induced by different components and different intermediates of QKLI in mice, it was preliminary believed that pseudoallergenic substances might exist in intermediate Isatidis Radix extracts and Gardenia extracts, but specific pseudoallergens shall be furthered studied in subsequent experiences.

[Mechanism of nephrotoxicity of rhubarb in rats].

The aim of this study was to investigate the renal toxicity of rhubarb and its mechanism. The SD rats were randomly divided into three groups: normal group and two rhubarb extract groups (16, 2 g·kg⁻¹). According to the dose conversion method between human and animal, rhubarb 16 g·kg⁻¹ and 2 g·kg⁻¹ were equivalent to 10 times and 1.25 times of human clinical dose respectively. Rhubarb extract was administered by a gastric gavage to rats once daily for 30 days. Serum urea nitrogen （BUN）, creatinine （CRE） and urine KIM-1, NGAL and renal morphology were analyzed. The expressions of OAT1, OAT3 and clusterin mRNA in kidney were measured. The results showed that the low dose of rhubarb had no obvious renal toxicity. The high dose group showed mild and moderate renal injury and a down-regulation of clusterin mRNA expression in the kidney tissue. The renal toxicity in male animals was heavier than that in female animals. There was no significant change in blood BUN and CRE in the high dose group. But urine NGAL level of the high dose group increased by 51.53% compared with normal group, of which male animals increased more significantly (P<0.05, compared with the normal group). The expressions of renal OAT1 and OAT3 mRNA in the low dose group were obviously higher than that in the normal group. The results indicated that the high dose of rhubarb could cause the renal toxicity. The dosage should be controlled reasonably in the clinical use. OAT1 and OAT3 mRNA related to anionic transport in kidney tissue played a compensatory protective role in rhubarb-induced renal injury. But the compensatory effect is relatively weak at the high dose level. In addition, routine renal function indicators BUN and CRE had limitation for monitoring the kidney toxicity of rhubarb. It is suggested that urine NGAL detection might be helpful for monitoring the renal toxicity of rhubarb.

Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness.

Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.

Evaluating a Web-Based Coaching Program Using Electronic Health Records for Patients With Chronic Obstructive Pulmonary Disease in China: Randomized Controlled Trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is now the fourth leading cause of death in the world, and it continues to increase in developing countries. The World Health Organization expects COPD to be the third most common cause of death in the world by 2020. Effective and continuous postdischarge care can help patients to maintain good health. The use of electronic health records (EHRs) as an element of community health care is new technology in China. OBJECTIVE: The aim of this study was to develop and evaluate a Web-based coaching program using EHRs for physical function and health-related quality of life for patients with COPD in China. METHODS: A randomized controlled trial was conducted from 2008 to 2015 at two hospitals. The control group received routine care and the intervention group received routine care with the addition of the Web-based coaching program using EHRs. These were used to manage patients' demographic and clinical variables, publish relevant information, and have communication between patients and health care providers. Participants were not blinded to group assignment. The effects of the intervention were evaluated by lung function, including percent of forced expiratory volume in 1 second (FEV1%), percent of forced vital capacity (FVC%), peak expiratory flow (PEF), maximum midexpiratory flow; St George's Respiratory Questionnaire (SGRQ); Modified Medical Research Council Dyspnea Scale (MMRC); and 6-Minute Walk Test (6MWT). Data were collected before the program, and at 1, 3, 6, and 12 months after the program. RESULTS: Of the 130 participants, 120 (92.3%) completed the 12-month follow-up program. There were statistically significant differences in lung function (FEV1%: F1,4=5.47, P=.002; FVC%: F1,4=3.06, P=.02; PEF: F1,4=12.49, P<.001), the total score of SGRQ (F1,4=23.30, P<.001), symptoms of SGRQ (F1,4=12.38, P<.001), the activity of SGRQ (F1,4=8.35, P<.001), the impact of SGRQ (F1,4=12.26, P<.001), MMRC (F1,4=47.94, P<.001), and 6MWT (F1,4=35.54, P<.001) between the two groups with the variation of time tendency. CONCLUSIONS: The Web-based coaching program using EHRs in China appears to be useful for patients with COPD when they are discharged from hospital into the community. It promotes the sharing of patients' medical information by hospital and community nurses, and achieves dynamic management and follow-up analysis for patients' disease. In addition, this program can postpone the decreasing rate of lung function, improve quality of life, decrease dyspnea, and increase physical capacity.

[Adverse reaction and screening of sensitizing substance of Shuxuening injection].

In this study, by the means of the active systemic allergy test in guinea pigs, passive skin allergy test in rats and pseudoallergic test in mice, it was determined that the "allergic reaction" of Shuxuening injection(SXNI) may not be a true IgE-mediated allergic reactions, but mainly of pseudoallergic reaction. Further pseudoallergic test proved that the pseudoallergic reactions of SXNI had difference between batches and showed dose dependence, so it was recommended to establish SXNI pseudoallergic reaction detection method for timely detecting and controlling the product risk of each batch products. In addition, as the pseudoallergic reactions of SXNI were dose-dependent, the dose and concentration of SXNI should be strictly controlled in clinical use. Then the main pseudoallergenic reaction test was conducted for the main monomer components in SXNI and the different fractions of Ginkgo biloba extract in mice, and the results showed that the sensitizing substances may mainly exist in YXY-3 fractions containing flavonol glycosides. By further chemically separating YXY-3, we got four chemical components. Among these four components, YXY-3-1 and YXY-3-2 were testified as the main allergenic components in SXNI through pseudoallergic test in mice. To make sure the specific chemical constituent that is responsible for the pseudoallergic reaction, in-depth study in follow-up experiments should be needed.

Identification and discrimination of binding sites of an organoruthenium anticancer complex to single-stranded oligonucleotides by mass spectrometry.

We here report the identification of the binding sites of an organometallic ruthenium anticancer complex [(η(6)-biphenyl)Ru(en)Cl](+) (1) to single-stranded oligodeoxynucleotides (ODNs) 5'-CCCA4G5C6CC-3' (I) and 5'-CCC3G4A5CCC-3' (II) by mass spectrometry. The MS analysis of exonuclease ladders demonstrated that the 5'-exonuclease bovine spleen phosphodiesterase digestion of I and II mono-ruthenated by complex 1 was arrested solely at A4 and partially at C3 and G4, respectively, and that the 3'-exonuclease snake venom phosphodiesterase digestion of the ruthenated ODNs was arrested solely at G5 and G4, respectively, due to the ruthenation. These results did not allow unambiguous identification of ruthenation sites on the metallated ODNs. In contrast, tandem mass spectrometry analysis with CID fragmentation of the mono-ruthenated ODNs provided sequential and complementary [a(i) - B]/wi fragments, leading to unambiguous identification of G5 in I and G4 in II as the ruthenation sites on the ODN adducts, which is in line with the high selectivity of the complex towards guanine base as reported previously. These findings suggest that caution should be raised with regard to the identification of the binding sites of metal complexes, in particular complexes with bulky ligands, like biphenyl in complex 1, to DNA by MS analysis of exonuclease ladders of the metallated adducts, because the bulky ligands may adopt such an orientation that they block the exonuclease cleavage of the 5'- or 3'-side phosphodiester bonds adjacent to the binding sites, leading to digestion stalling at the nucleotides before the binding sites.

Enrichment and enumeration of circulating tumor cells by efficient depletion of leukocyte fractions.

BACKGROUND: Enumeration and characterization of circulating tumor cells (CTCs) can provide information on patient prognosis and treatment efficacy. However, CTCs are rare, making their isolation a major technological challenge. We developed a technique for enrichment, and subsequent characterization of CTCs based on efficient depletion of human leukocytes. METHODS: The technique (CanPatrolTM CTC enrichment) we developed is based on red blood cell lysis to remove erythrocytes, followed by depletion of CD45+ leukocytes using a magnetic bead separation method, and subsequent isolation of CTCs by virtue of their larger size, compared with leukocytes. We also demonstrated that fluorescence in situ hybridization (FISH) and genetic abnormalities analysis could be performed on the isolated CTCs. RESULTS: The spiking experiments showed that the average efficacy of leukocytes depletion was 99.98% and the average tumor cells recovery was not lower than 80%. FISH could be used to perform ALK gene rearrangement analysis on the collected NCI-H2228 cells, and EGFR Exon 19 deletion was detected by PCR-based analysis in isolated HCC827 cells. The in vivo feasibility of this technique had been demonstrated in patients with non-small cell lung cancer, breast, colon, and esophageal cancers. CTCs were detected in 13 of 59 blood samples. Tumor microemboli was also detected in three breast cancer samples. CONCLUSIONS: The technique we developed allowed isolation and characterization of circulating epithelial tumor cells that do not express classical epithelial antigens. This potentially leads to a more accurate enumeration of the number of CTCs and is suitable for application to a broad range of cancers.

Effect of a Health Belief Model-based nursing intervention on Chinese patients with moderate to severe chronic obstructive pulmonary disease: a randomised controlled trial.

AIMS AND OBJECTIVES: To test the effect of a Health Belief Model-based nursing intervention on healthcare outcomes in Chinese patients with moderate to severe COPD. BACKGROUND: The Health Belief Model (HBM) has been internationally validated in a variety of chronic conditions. However, nursing intervention based on the HBM is less explored in Chinese patients with COPD. DESIGN: A randomised controlled trial. METHODS: Enrolled patients were randomly assigned to the intervention and control groups. Patients in the intervention group received a 20- to 30-minute HBM-based nursing intervention every 2 days during the hospitalisation period after disease conditions were stable, with additional follow-ups after discharge. Patients in the control group received routine nursing care. RESULTS: Patients had significantly increased scores of health belief and self-efficacy after receiving the HBM-based nursing intervention. After receiving the 3-month follow-up, patients in the intervention group had significantly higher mean total scores in the Health Belief Scale and the COPD Self-Efficacy Scale, as well as in all the subscales, than those in the control group except the perceived disease seriousness. Results showed that the value of FEV1 /FVC ratio had a significant difference between study groups before and after the intervention. Results also indicated that mean scores of the Dyspnea Scale, 6-minute walking distance and ADL were significantly different between the groups and between the study time-points. CONCLUSIONS: Among patients with moderate to severe COPD, nursing intervention based on the HBM can enhance their health belief and self-efficacy towards the disease management, decrease dyspnoea and improve exercise tolerance and ADL. RELEVANCE TO CLINICAL PRACTICE: Nurses can use the HBM-based intervention to enhance patients' health belief and self-efficacy towards the management of COPD, and subsequently benefit healthcare outcomes.