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We have previously shown that a mixture of cerebrosides obtained from dried tubers of herb Typhonium giganteum Engl. plays a neuroprotective role in the ischemic brain through its effect on activation of BK(Ca) channels. It is very curious to know whether a single pure cerebroside compound could activate the BK(Ca) channel as well. This study explored the possible effects of pure cerebroside compounds, termitomycesphins A and B, on the BK(Ca) channel activation. Both termitomycesphins A and B activated the BK(Ca) channels at micromole concentration without significant difference. Termitomycesphin A increased the single channel open probability of the BK(Ca) channels in a dose-dependent manner without modifying the single channel conductance. Termitomycesphin A activated BK(Ca) channel more efficiently when it was applied to the cytoplasmic face of the membrane, suggesting that binding site for termitomycesphin A is located at the cytoplasmic side. Termitomycesphin A shifted the voltage-dependent activation curve to less positive membrane potentials and the Ca(2+)-dependent activation curve of the channel upwards, suggesting that termitomycesphin A could activate the channels even without intracellular free Ca(2+). Furthermore, STREX-deleted BK(Ca) channels were completely insensitive to termitomycesphin A, indicating that STREX domain is required for the activation of the BK(Ca) channel. These data provide evidence that termitomycesphins are potent in stimulating the activity of the BK(Ca) channels. As BK(Ca) channels are associated with pathology of many diseases, termitomycesphins might be used as therapeutic agents for treating these diseases through its regulatory effect on the BK(Ca) channels.

Praeruptorin A (PA) is a pyranocoumarin compound isolated from the dried root of Peucedanum praeruptorum Dunn (Umbelliferae). However, the antiinflammatory effect of PA has not been reported. The present study investigated the antiinflammatory effect of PA in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. PA significantly inhibited the LPS-induced production of nitric oxide (NO), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The mRNA and protein expressions of inducible nitric oxide synthase (iNOS), IL-1β and TNF-α were also suppressed by this compound. Further study showed that PA decreased the cytoplasmic loss of inhibitor κB-α (IκB-α) protein and inhibited the translocation of NF-κB from cytoplasm to nucleus. Taken together, the results suggest that PA may exert antiinflammatory effects in vitro in LPS-stimulated RAW 264.7 macrophages through inhibition of NF-κB signal pathway activation.

Ambient air pollution has been linked to cardiovascular and respiratory morbidity and mortality in epidemiology studies. Frequently, oxidative and nitrosative stress are hypothesized to mediate these pollution effects, however precise mechanisms remain unclear. This paper describes the methodology for a major panel study to examine air pollution effects on these and other mechanistic pathways. The study took place during the drastic air pollution changes accompanying the 2008 Olympics in Beijing, China. After a general description of air pollution health effects, we provide a discussion of panel studies and describe the unique features of this study that make it likely to provide compelling results. This study should lead to a clearer and more precise definition of the role of oxidative and nitrosative stress, as well as other mechanisms, in determining acute morbidity and mortality from air pollution exposure.

To investigate whether geniposide, an iridoid glucoside extracted from gardenia jasminoides ellis fruits, inhibits cell adhesion to human umbilical vein endothelial cells (HUVECs) induced by high glucose and its underlying mechanisms.HUVECs were isolated from human umbilical cords and cultured. The adhesion of monocytes to HUVECs was determined using fluorescence-labeled monocytes. The mRNA and protein levels of vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) were measured using real-time RT-PCR and ELISA. Reactive oxygen species (ROS) production was measured using a fluorescent probe. The amounts of nuclear factor-kappa B (NF-kappaB) and inhibitory factor of NF-kappaB (IkappaB) were determined using Western blot analysis. The translocation of NF-kappaB from the cytoplasm to the nucleus was determined using immunofluorescence.Geniposide (10-20 mumol/L) inhibited high glucose (33 mmol/L)-induced adhesion of monocytes to HUVECs in a dose-dependent manner. This compound (5-40 mumol/L) also inhibited high glucose-induced expression of VCAM-1 and E-selectin at the gene and protein levels. Furthermore, geniposide (5-20 micromol/L) decreased ROS production and prevented IkappaB degradation in the cytoplasm and NF-kappaB translocation from the cytoplasm to the nucleus in HUVECs.Geniposide inhibits the adhesion of monocytes to HUVECs and the expression of CAMs induced by high glucose, suggesting that the compound may represent a new treatment for diabetic vascular injury. The mechanism underlying this inhibitory effect may be related to the inhibition of ROS overproduction and NF-kappaB signaling pathway activation by geniposide.

An automatic sleep staging method is proposed to score wakefulness and three nonrapid eye movement (NREM) stages S1, S2 and S3, based on the Empirical Mode Decomposition (EMD) algorithm. Patients with sleep disorders were tested using this method. Good agreements between manual and automatic staging results were achieved in terms of their Cohen's Kappa value.

Two new alkyl 2,3-dihydroxybenzoates, gentisides A and B, were isolated from the traditional Chinese medicine Gentiana rigescens Franch. Their structures and stereochemistry were elucidated by spectroscopic methods and chemical derivatization. These compounds showed a significant neuritogenic activity at 30 microM against PC12 cells that was comparable to that seen for the best nerve growth factor (NGF) concentration of 40 ng/mL. Gentisides A and B showed parallel activity, indicating that the observed structural difference at the end of their alkyl chain did not affect neuritogenic activity.

Rationale Recently, Talaromyces marneffei (T. marneffei) has been reported in human immunodeficiency virus (HIV)-negative patient with underlying diseases, such as oral cancer, colon cancer, haematological malignancies, connective tissue disease, diabetes mellitus, and corticosteroids or immunosuppressive agents. Similar to HIV-positive ones, such patients were observed with CD4 lymphocytopenia. Patient concerns We reported a case of a 45-year-old woman who was diagnosed with disseminated T. marneffei and Mycobacteria kansasii (M. kansasii) with papillary thyroid cancer as the underlying disease. T-cell subsets counts, CD4 T-cell%, CD8 T-cell%, CD4/CD8 ratio, and NK cell% were all turned out to be normal. Diagnoses Based on bronchoalveolar lavage fluid and skin lesions secretion cultures, blood culture, the patient was diagnosed with disseminated T. marneffei and M. kansasii. Pathological examination reported papillary thyroid cancer with cervical lymph node metastasis. Interventions The patient received the combined and longer antifungal therapy and drug regimens for M. kansasii. She had total thyroidectomy with radical neck dissection to treat the papillary thyroid cancer. Outcomes The patient had a favorable outcome for 19 months without recurrence. Lessons T. marneffei could infect non-HIV individuals with underlying disease under the condition of normal T-cell counts. The symptoms were lack of specificity and were more likely to be misdiagnosed. Such patients with unidentified T-cell dysfunction or other unidentified primary immunodeficiency disorders may prone to coinfect with other opportunistic pathogens, such as M. kansasii. Compared with HIV-positive ones, they need combined and much longer antifungal therapy.

Aim: Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) are important in control of blood glucose homeostasis, and are considered to be potential targets for antidiabetic drugs. Astragaloside IV has been reported to have a hypoglycemic effect. However, the biochemical mechanisms by which astragaloside IV regulates hepatic glucose-metabolizing enzymes remain unknown. The present study examines whether GP and G6Pase mediate the hypoglycemic effect of astragaloside IV. Methods: Type 2 diabetic mice were treated with astragaloside IV for 2 weeks. Blood glucose and insulin levels were measured by a glucometer and the ELISA method, respectively. Total cholesterol (TC) and triglyceride (TG) levels were determined using LabassayTM kits. Activities of hepatic GP and G6Pase were measured by the glucose-6-phosphate dehydrogenase-coupled reaction. The mRNA and protein levels of both enzymes were determined by real-time RT-PCR and Western blotting. Results: Astragaloside IV at 25 and 50 mg/kg significally decreased the blood glucose, TG and insulin levels, and inhibited the mRNA and protein expression as well as enzyme activity of GP and G6Pase in diabetic mice. Conclusions: Astragaloside IV exhibited a hypoglycemic effect in diabetic mice. The hypoglycemic effect of this compound may be explained, in part, by its inhibition of hepatic GP and G6Pase activities. Copyright © 2009 John Wiley & Sons, Ltd.

Exocytosis of endothelial Weibel-Palade bodies, which contain von Willebrand factor (VWF), P-selectin and other modulators, plays an important role in both inflammation and thrombosis. The present study investigates whether genipin, an aglycon of geniposide, inhibits endothelial exocytosis. Human umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords and cultured. The concentration of VWF in cell supernatants was measured using an ELISA Kit. P-selectin translocation on the cell surface was analyzed by cell surface ELISA. Cell viability was measured using a Cell Counting Kit-8. Mouse bleeding times were measured by amputating the tail tip. Western blot analysis was used to determine the amount of endothelial nitric oxide synthase (eNOS) and phospho-eNOS present. Nitric oxide (NO) was measured in the cell supernatants as nitrite using an NO Colorimetric Assay. Genipin inhibited thrombin-induced VWF release and P-selectin translocation in HUVECs in a dose- and time-dependent manner. The drug had no cytotoxic effect on the cells at the same doses that were able to inhibit exocytosis. The functional study that demonstrated that genipin inhibited exocytosis in vivo also showed that genipin prolonged the mouse bleeding time. Furthermore, genipin activated eNOS phosphorylation, promoted enzyme activation and increased NO production. L-NAME, an inhibitor of NOS, reversed the inhibitory effects of genipin on endothelial exocytosis. Genipin inhibits endothelial exocytosis in HUVECs. The mechanism by which this compound inhibits exocytosis may be related to its ability to stimulate eNOS activation and NO production. Our findings suggest a novel anti-inflammatory mechanism for genipin. This compound may represent a new treatment for inflammation and/or thrombosis in which excess endothelial exocytosis plays a pathophysiological role.

Convenient synthesis of an N-glycan octasaccharide (A) of the bisecting type was described. The stable and easily prepared orthoester F, 3''-O-chloroacetyl-4'',6''-O-benzylidene-alpha-D-glucopyranose 1'',2''-(chloromethyl 3',6'-di-O-benzyl-2'-deoxy-2'-phthalimido-beta-D-glucopyranosyl-(1--4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosylazide-4'-yl orthoacetate), was designed as the key intermediate with two advantages: (1) distinguishing OH-2'' from OH-3'' in beta-D-glucopyranoside to construct the central beta-D-mannopyranoside by inverting the configuration of OH-2'' in beta-D-glucopyranoside and (2) distinguishing OH-4'' and OH-6'' from OH-3'' in the beta-D-mannopyranoside to introduce the bisecting GlcNAc residue.

Recent studies revealed that unstable ventilation control is one of mechanisms underlying the occurrence of sleep apnea. Thus, we investigated whether TASK-1, an acid-sensitive potassium channel, plays a role in the occurrence of sleep apnea. First, the expression of TASK-1 transcriptions on brainstem was checked by in situ hybridization. Then, the correlation between the central apneic episodes and protein contents of TASK-1 measured by western blot was analyzed from 27 male rats. Results showed that TASK-1 mRNAs were widely distributed on the putative central chemoreceptors such as locus coeruleus, nucleus tractus solitarius and medullary raphe, etc. Both the total spontaneous apnea index (TSAI) and spontaneous apnea index in NREM sleep (NSAI) were positively correlated with TASK-1 protein contents (r=0.547 and 0.601, respectively, p

To investigate the influence of the S447X variant in lipoprotein lipase (LPL) gene on the response rate to therapy with the thiazolidinedione pioglitazone. A total of 113 diabetic patients were treated with pioglitazone 30 mg for 10 weeks. Response to the pioglitazone treatment was defined by either a >10% relative reduction in fasting blood glucose (FBG) or a more than 1% decrease in glycosylated haemoglobin (HbA1c) values after 10 weeks of pioglitazone treatment. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method. Using the criteria >10% relative reduction in FBG after 10 weeks of pioglitaone treatment, responder frequency to pioglitazone treatment in S447S genotype group is significantly higher than S447X genotype group. Meanwhile, the S447X genotype conferred a statistically significant 0.538-fold reduction in response rate to pioglitazone treatment relative to the S447S genotype. Moreover, pioglitazone treatment has significantly beneficial effects on serum lipid profile and blood pressure in S447S genotype carriers. The S447X variant in LPL gene may be a cause for therapy modification by pioglitazone.

To investigate risk factors correlated to the decline of FEV₁among community population in the urban area of Beijing.Subjects no younger than 40 years old were recruited from three communities in the urban area of Beijing. All of them were asked to fill in a questionnaire in regard to general health conditions, past medical history, medication usage, smoking history, etc. FEV₁and FEV6 were measured by Vitalograph COPD-6 spirometer using the standard protocol. Two years after the first visit, questionnaire survey and spirometry were repeated.Four hundred and fifty two subjects fulfilled the inclusion criteria and finished the 2nd visit, with an average age of (58.8 ± 8.6) years, 29% male and 71% female. The mean decline rate of FEV₁in the cohort was (43 ± 114) ml per year. There was no significant difference of mean FEV₁decline between different gender and age groups. A mean decline of FEV₁by (64 ± 125) ml per year was observed in smokers (including former smokers and current smokers) whereas the decline rate in non-smokers was (36 ± 109) ml per year (P = 0.030). There was no significant statistical difference among current smokers, former smokers, passive smokers and subjects who never smoke. A higher decline rate of FEV₁was observed in subjects with a history of COPD or airway hyperreactivity, chronic cough, diabetes, hypertension and coronary heart disease. The difference, however, was not statistically significant. Binary logistic regression was used to screen risk factors affected the FEV₁decline rate between rapid decline (ΔFEV1 ≥ 30 ml/y) and non-rapid decline (ΔFEV130 ml/y), and found smoking was an independent risk factor of FEV₁decline rate.The mean rate of FEV1 decline in 2.6 years in the surveyed community population in the urban area of Beijing was (43 ± 114) ml per year; Smoking is an independent risk factor of FEV₁decline.

Objectives For patients with obstructive sleep apnea hypopnea syndrome (OSAHS), chronic inflammation and hemodynamic oscillations caused by respiratory events contribute to cardiovascular disease (CVD). In this study, a physiological marker named oscillatory coupling factor (OCF) exacted from cardiac output (CO) was introduced. This study aimed to evaluate the clinical value of OCF and tentatively explore its predictive value of cardiovascular prognosis in OSAHS patients. Methods An impedance cardiogram (ICG) was used to continuously obtain the participants' CO with simultaneous polysomnography. Participants were divided into three groups: an OSAHS–CVD– group ( n = 19); an OSAHS + CVD– group ( n = 34); and an OSAHS + CVD + group ( n = 36). The OCF was exacted from the CO by using empirical mode decompensation-based detrended fluctuation analysis (EMD–DFA). Results The OCF values were: OSAHS + CVD + group [1.20 (0.98–1.78)] > OSAHS + CVD– group [1.14 (1.02–1.94)] > OSAHS–CVD– group [0.95 (0.56–1.16)], ( p = 0.001). A Spearman test showed that OCF was positively correlated with age, apnea/hypopnea index (AHI), microarousal index (MAI), oxygen desaturation index (ODI), and negatively correlated with the lowest SpO 2 . Ten participants were treated by one-night continuous positive airway pressure (CPAP): their AHI decreased from 44.9 (18.0–72.9)/hour to 1.25 (0.0–7.5)/hour, and their OCF fell from 1.17 (1.10–1.69) to 1.08 (0.96–1.23) ( p = 0.038). Seventy-seven participants were effectively followed up. Seven participants developed CVD events or newly diagnosed CVD; their OCFs were distributed on a relatively high level [1.18 (1.01–1.56)]. Conclusion The OSAHS participants had higher OCFs than those without OSAHS, while CVD made the OCFs even higher; CPAP could rectify this change. Oscillatory coupling factor may be a physiological marker of cardiopulmonary coupling and have potential cardiovascular prognostic value for people with OSAHS.

The focus of this work is the synthesis of an ursolic acid saponin with an N-acetylglucosamine-containing trisaccharide residue. Therefore, ursolic acid 3-yl α-L-arabinopyranosyl-(12)-α-L-arabinopyranosyl-(16)-2-acetamido-2-deoxy-β-D-glucopyranoside (1) was concisely synthesized in convergent synthesis with 48.0% overall yield. The structure of saponin 1 was confirmed by 1H NMR, 13C NMR and mass spectra.

The aim of this study was to observe the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in sarcoidosis.We retrospectively analyzed the diagnostic efficiency of standard bronchoscopy and EBUS-TBNA in all patients diagnosed as sarcoidosis in Peking University First Hospitals between August 2010 and October 2011. The relationship between biopsy puncture numbers and sensitivity was calculated.There were 17 sarcoidosis patients among a total of 107 patients who had received EBUS-TBNA. Forteen patients had a positive TBNA result and the sensitive of EBUS-TBNA was 82%. The sensitivity of standard brochoscopy was 53% and when combined with EBUS-TBNA, the sensitivity increased to 88%. The sensitivity of EBUS-TBNA was associated with the size of lymph nodes. Lymph nodes with a diameter ≥ 2 cm showed a higher positive rate. Four punctures for 1 lymph node showed a concordance rate of 100% with the final results.EBUS-TBNA was a safe and effective method in diagnosing pulmonary sarcoidosis. For patients with suspected sarcoidosis EBUS-TBNA should be performed in the largest lymph nodes with at least 4 punctures.

To describe the clinical features of mixed types of pulmonary aspergillosis (MTPA), and therefore to improve the diagnosis and treatment of MTPA.This study retrospectively analyzed 3 patients with MTPA in Peking University First Hospital from November 2010 to 2012. "Invasive pulmonary aspergillosis (IPA), pulmonary aspergilloma, allergic bronchopulmonary aspergillosis (ABPA)" were used as the Chinese and English keywords, to search the literatures from Wanfang database and Pubmed database until to May 2014.There were 3 patients with MTPA, respectively with aspergilloma and IPA (patient 1), ABPA and IPA (patient 2), aspergilloma and IPA (patient 3). The cultures of respiratory secretions of the patients all yielded A.fumigatus. Patient 1 was treated by amphotericin B; Patient 2 was treated by intravenous itraconazole and glucocorticoid; Patient 3 was treated by oral voriconazole and inhaled corticosteroid, and the aspergilloma was surgically removed at the same time. Eventually, patients 1 and 2 died, while the symptoms of patient 3 were significantly improved. Drug sensitivity test of A. fumigatus showed resistance to amphotericin B or itraconazole. By far there was no concept of MTPA in the literatures and there were only 3 relevant case reports.MTPA is a new subtype of pulmonary aspergillosis, which is more complicated and severe, and perhaps with drug resistance. MTPA should be treated by comprehensive therapies on the basis of sensitive and effective antifungal drugs.

Continuous positive airway pressure (CPAP) is currently the most effective treatment method for obstructive sleep apnea syndrome (OSAS). The purpose of this study was to compare the sleep electroencephalogram (EEG) changes before and after the application of CPAP to OSAS patients. A retrospective study was conducted and 45 sequential patients who received both polysomnography (PSG) and CPAP titration were included. The raw data of sleep EEG were extracted and analyzed by engineers using two main factors: fractal dimension (FD) and the zero-crossing rate of detrended FD (zDFD). FD was an effective indicator reflecting the EEG complexity and zDFD was useful to reflect the variability of the EEG complexity. The FD and zDFD indexes of sleep EEG of 45 OSAS patients before and after CPAP titration were analyzed. The age of 45 OSAS patients was 52.7 ± 5.6 years old and the patients include 12 females and 33 males. After CPAP treatment, FD of EEG in non-rapid eye movement (NREM) sleep decreased significantly (P

To explore the correlation between SIRT1 expression in brainstem and apnea hypopnea index and the effect of hypoxia on SIRT1 expression in rats.Thirty-three healthy Sprague-Dawley(SD) rats underwent sleep monitoring and SIRT1 protein in brainstems was measured by Western blot. The correlation of sleep apnea index and SIRT1 protein level in brainstem was analysed. Another 36 adult male SD rats were randomly and equally divided into 4 groups: normal control (NC) group, continuous hypoxia (CH) group, intermittent hypoxia (IH) group and intermittent hypoxia with hypercapnia (IHH) group. The expression of SIRT1 protein of the lower brainstems of the 4 groups were measured by Western blot.The level of SIRT1 in the brainstem was negatively correlated with the frequency of spontaneous sleep apnea in REM(r = -0.617, P0.001) while positively correlated with the frequency of post sigh sleep apnea in REM (r = 0.535, P0.01). The relative expression level of SIRT1 in NC, CH, IH, IHH group were (1.4 ± 1.0), (1.4 ± 0.6), (2.5 ± 1.0) , (1.6 ± 1.2), respectively. There was a significant difference in the SIRT1 level among groups (F = 2.964, P0.05) .The rats with lower level of SIRT1 may have lower anti-oxidative stress capability which results in higher frequency of spontaneous sleep apnea. Under the circumstance of hypoxia, the fact that the expression of SIRT1 protein was elevated may be a protective mechanism.

Recent studies showed the central Na+/H+ exchanger type 3 (NHE3) has a close relationship with ventilation control. The objective of the study is to investigate the role of NHE3 in sleep apnea in Sprague-Dawley (SD) rats.A sleep study was performed on 20 male SD rats to analyze the correlation between the sleep apneic events and total NHE3 protein content and inactive NHE3(pS552) in the brainstem measured by Western blotting. Another 20 adult male SD rats received 3 days of sleep and respiration monitoring for 6 hours a day, with adaption on the first day, 0.5% DMSO microinjection into the fourth ventricle on the second day, and AVE0657 (specific inhibitor of NHE3) microinjection on the third day. Rats were divided into two groups with injection of 5 µmol/L or 8 µmol/L AVE0657 before the sleep study. The effects of AVE0657 on sleep apnea and sleep structure of rats were analyzed through self-control.The total post-sigh apnea index (TPSAI) and post-sigh apnea index in non-rapid eye movement (NREM) sleep (NPSAI) and total apnea index (AI) in NREM sleep (NAI) were negatively correlated with NHE3(pS552) protein contents in the brainstem (r = -0.534, -0.547 and -0.505, respectively, P0.05). The spontaneous apnea index in REM sleep (RSPAI) was positively correlated with the level of NHE3(pS552) protein expression in the brainstem (r = 0.556, P0.05). However, the sleep AI had no relationship with total NHE3 protein. Compared with the blank control and microinjection of 0.5% DMSO, 5 µmol/L AVE0657 significantly reduced the total AI and NPSAI (both P0.05) without a significant effect on sleep architecture. In contrast to blank control and microinjection of 0.5% DMSO, injection of 8 µmol/L AVE0657 significantly reduced the AI and PSAI in NREM and REM sleep (all P0.05).The severity of sleep apnea was negatively correlated with central inactive NHE3. A specific inhibitor of NHE3 decreased the sleep AI. Thus, our results indicate that central NHE3 might be a molecular target for sleep apnea treatment, whose inhibitors may be potential therapeutic drugs for sleep apnea.

Very recent studies revealed that obstructive sleep apnoea (OSA) is a contributor of the increased incidence and mortality of cancer in humans, but mechanisms of how OSA promotes tumorigenesis remains largely unknown. We investigated whether intermittent hypoxia with and without hypercapnia plays a role in tumorigenesis.First, Sprague-Dawley (SD) male rats (12 weeks old) were subjected to different hypoxia exposures: intermittent hypoxia and intermittent hypoxia with hypercapnia; continuous hypoxia and normal air. The systemic application of chronic fast rate hypoxia with or without hypercapnia mimicked severe OSA patients with apnoea/hypopnea index equivalent to 60 events per hour. Then routine blood tests were performed and the levels of brain derived neurotrophic factor (BDNF) and miR-34a were examined.In contrast to intermittent hypoxia with hypercapnia, both intermittent hypoxia and continuous hypoxia treatments caused significantly higher levels of haematology parameters than normoxia treatments. Compared to normoxia, intermittent hypoxia with hypercapnia exposure resulted in substantial decrease of serum BDNF and, miR-34a in the lower brainstem, while less pronounced results were found in intermittent hypoxia and continuous hypoxia exposure.The exposure of intermittent hypoxia with or without hypercapnia, mimicking the situations in severe OSA patients, was associated with, or even promoted tumorigenesis.

Anaplastic lymphoma kinase (ALK) negative anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin's lymphoma (NHL). Pulmonary infiltration with multiple nodules is an unusual manifestation. We present an adult patient who had diffuse lung and bone marrow involvement and review the pulmonary manifestation of ALCL. The present reports suggest that diffuse lung infiltration is associated with a bad clinical outcome.

Associations between air pollution and cardiorespiratory mortality and morbidity have been well established, but data to support biologic mechanisms underlying these associations are limited. We designed this study to examine several prominently hypothesized mechanisms by assessing Beijing residents' biologic responses, at the biomarker level, to drastic changes in air quality brought about by unprecedented air pollution control measures implemented during the 2008 Beijing Olympics. To test the hypothesis that changes in air pollution levels are associated with changes in biomarker levels reflecting inflammation, hemostasis, oxidative stress, and autonomic tone, we recruited and retained 125 nonsmoking adults (19 to 33 years old) free of cardiorespiratory and other chronic diseases. Using the combination of a quasi-experimental design and a panel-study approach, we measured biomarkers of autonomic dysfunction (heart rate [HR*] and heart rate variability [HRV]), of systemic inflammation and oxidative stress (plasma C-reactive protein [CRP], fibrinogen, blood cell counts and differentials, and urinary 8-hydroxy-2'-deoxyguanosine [8-OHdG]), of pulmonary inflammation and oxidative stress (fractional exhaled nitric oxide [FeNO], exhaled breath condensate [EBC] pH, EBC nitrate, EBC nitrite, EBC nitrite+nitrate [sum of the concentrations of nitrite and nitrate], and EBC 8-isoprostane), of hemostasis (platelet activation [plasma sCD62P and sCD40L], platelet aggregation, and von Willebrand factor [vWF]), and of blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). These biomarkers were measured on each subject twice before, twice during, and twice after the Beijing Olympics. For each subject, repeated measurements were separated by at least one week to avoid potential residual effects from a prior measurement. We measured a large suite of air pollutants (PM2.5 [particulate matteror = 2.5 microm in aerodynamic diameter] and constituents, sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], and ozone [O3]) throughout the study at a central Beijing site near the residences and workplaces of the subjects on a daily basis. Total particle number (TPN) was also measured at a separate site. We used a time-series analysis to assess changes in pollutant concentration by period (pre-, during-, and post-Olympics periods). We used mixed-effects models to assess changes in biomarker levels by period and to estimate changes associated with increases in pollutant concentrations, controlling for ambient temperature, relative humidity (RH), sex, and the day of the week of the biomarker measurements. We conducted sensitivity analyses to assess the impact of potential temporal confounding and exposure misclassification. We observed reductions in mean concentrations for all measured pollutants except O3 from the pre-Olympics period to the during-Olympics period. On average, elemental carbon (EC) changed by -36%, TPN by -22%, SO2 by -60%, CO by -48%, and NO2 by -43% (P0.05 for all these pollutants). Reductions were observed in mean concentrations of PM2.5 (by -27%), sulfate (SO4(2-)) (by -13%), and organic carbon (OC) (by -23%); however, these values were not statistically significant. Both 24-hour averages and 1-hour maximums of O3 increased (by 20% and 17%, respectively) from the pre-Olympics to the during-Olympics period. In the post-Olympics period after the pollution control measures were relaxed, mean concentrations of most pollutants (with the exception of SO4(2-) and O3) increased to levels similar to or higher than pre-Olympics levels. Concomitantly and consistent with the hypothesis, we observed, from the pre-Olympics to the during-Olympics period, statistically significant (Por = 0.05) or marginally significant (0.05P0.1) decreases in HR (-1 bpm or -1.7% [95% CI, -3.4 to -0.1]), SBP (-1.6 mmHg or -1.8% [95% CI, -3.9 to 0.4]), 8-OHdG (-58.3% [95% CI, -72.5 to -36.7]), FeNO (-60.3% [95% CI, -66.0 to -53.6]), EBC nitrite (-30.0% [95% CI, -39.3 to -19.3]), EBC nitrate (-21.5% [95% CI, -35.5 to -4.5]), EBC nitrite+nitrate (-17.6% [95% CI, -28.4 to -5.1]), EBC hydrogen ions (-46% [calculated from EBC pH], or +3.5% in EBC pH [95% CI, 2.2 to 4.9]), sCD62P (-34% [95% CI, -38.4 to -29.2]), sCD40L (-5.7% [95% CI, -10.5 to -0.7]), and vWF (-13.1% [95% CI, -18.6 to -7.5]). Moreover, the percentages of above-detection values out of all observations were significantly lower for plasma CRP and EBC 8-isoprostane in the during-Olympics period compared with the pre-Olympics period. In the post-Olympics period, the levels of the following biomarkers reversed (increased, either with or without statistical significance) from those in the during-Olympics period: SBP (10.7% [95% CI, 2.8 to 18.6]), fibrinogen (4.3% [95% CI, -1.7 to 10.2), neutrophil count (4.7% [95% CI, -7.7 to 17.0]), 8-OHdG (315% [95% CI, 62.0 to 962]), FeNO (130% [95% CI, 62.5 to 225]), EBC nitrite (159% [95% CI, 71.8 to 292]), EBC nitrate (161% [95% CI, 48.0 to 362]), EBC nitrite+nitrate (124% [95% CI, 50.9 to 233]), EBC hydrogen ions (146% [calculated from EBC pH] or -4.8% in EBC pH [95% CI, -9.4 to -0.21), sCD62P (33.7% [95% CI, 17.7 to 51.8]), and sCD40L (9.1% [95% CI, -3.7 to 23.5]). Furthermore, these biomarkers also showed statistically significant associations with multiple pollutants across different lags after adjusting for meteorologic parameters. The associations were in the directions hypothesized and were consistent with the findings from the comparisons between periods, providing further evidence that the period effects were due to changes in air quality, independent of season and meteorologic conditions or other potential confounders. Contrary to our hypothesis, however, we observed increases in platelet aggregation, red blood cells (RBCs) and white blood cells (WBCs) associated with the during-Olympics period, as well as significant negative associations of these biomarkers with pollutant concentrations. We did not observe significant changes in any of the HRV indices and DBP by period. However, we observed associations between a few HRV indices and pollutant concentrations. Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of pulmonary and systemic inflammation, oxidative stress, and hemostasis and in measures of cardiovascular physiology (HR and SBP) in healthy, young adults. These changes support the prominently hypothesized mechanistic pathways underlying the cardiorespiratory effects of air pollution.

Underlying mechanisms by which air pollutants adversely affect human health remain poorly understood. Oxidative stress has been considered as a potential mechanism that may promote lipid peroxidation by reactive oxygen species, leading to the formation of malondialdehyde (MDA) that is excreted in biofluids (e.g., urine and exhaled breath condensate (EBC)). A panel study was conducted to examine whether concentrations of MDA in EBC and urine were associated, respectively, with changes in air pollution levels brought by the Beijing Olympic air pollution control measures. EBC and urine samples from 125 healthy adults were collected twice in each of the pre-, during-, and post-Olympic periods. Period-specific means of MDA and changes in MDA levels associated with increases in 24-h average pollutant concentrations were estimated using linear mixed-effects models. From the pre- to the during-Olympic period, when concentrations of most pollutants decreased, EBC MDA and urinary MDA significantly decreased by 24% (P < 0.0001) and 28% (P = 0.0002), respectively. From the during-Olympic to the post-Olympic period, when concentrations of most pollutants increased, EBC MDA and urinary MDA increased by 28% (P = 0.094) and 55% (P = 0.046), respectively. Furthermore, the largest increases in EBC MDA associated with one interquartile range (IQR) increases in all pollutants but ozone ranged from 10% (95% CI: 2%, 18%) to 19% (95% CI: 14%, 25%). The largest increases in urinary MDA associated with IQR increases in pollutant concentration ranged from 9% (95%: 0.3%, 19%) to 15% (95% CI: 3%, 28%). These findings support the utility of EBC MDA as a biomarker of oxidative stress in the respiratory tract and urinary MDA as a biomarker of systemic oxidative stress in relation to air pollution exposure in healthy young adults. Both EBC and urine samples can be collected noninvasively in the general population.

Epidemiologic studies have reported the association between fine particles (aerodynamic diameter ≤ 2.5 μm; PM2.5) and health effects, but the immunological mechanisms are not clear. To investigate the dose and time-dependent role of toll-like receptor (TLR) and Th1/Th2 shift in local and systemic inflammation induced by PM2.5, mice were subjected to intratracheal instillation of 2.5, 5, or 10 mg/kg PM2.5 in this study. After 24 h, 72 h, 7 days, and 14 days, mice were sacrificed to measure TLR2 and TLR4 expressions and Th1/Th2 related cytokines in bronchoalveolar lavage fluid (BALF) and peripheral blood. Histopathological changes in lung were also examined. Inflammatory infiltration and macrophages with engulfed particles were found by lung histopathology after PM2.5 exposure. TLR4 positive cells decreased in BALF but increased in blood at 24 h after the exposure. The low percentage of TLR4 positive cells continued to day 14 in BALF, but recovered at day 7 and decreased further to lower than the control value at day 14 in blood. TLR2 positive cell changed similar to TLR4 in BALF on the dose effects. In BALF at 24 h after the exposure, the Th2 related cytokines IL-5 and IL-10 increased dose-dependently; and in blood, the Th2 related cytokines IL-4, IL-5, and IL-10 also increased. These results suggest that acute exposure of PM2.5 leads to acute inflammatory responses locally and systemically in mice. TLR2 and TLR4 are involved in this process and PM2.5 can drive a Th2-biased immune response.

In this study we applied statistical multivariate analysis techniques to establish correlations between material properties and tablet tensile strength (TS) of microcrystalline cellulose (MCC) with different types and manufacturers. There were sixteen MCC samples included in this analysis described by 22 material parameters. For data analysis, principal component analysis (PCA) was used to model and evaluate the various relationships between the material properties and TS. Furthermore, partial least squares regression (PLS) analysis was performed to quantify the relationships between the material properties and TS and to predict the most influential MCC parameters contributing to the compactibility. The results showed that the moisture content, hygroscopicity and crystallinity did not exhibit significant impact on TS. The turgidity, maximum water uptake, degree of polymerization and molecular weight presented a strong positive influence on TS, while the density property, bulk and tap density, exhibited an obvious negative impact. The present work demonstrated that multivariate data analysis techniques (PCA and PLS) are useful for interpreting complex relations between 22 material properties and the tabletting properties of MCC. Furthermore, the method can be used for material classification.

Summary The dynamics of programmed death-1 (PD-1) as well as cytokine/chemokine expression and its correlation with virological response in patients with chronic hepatitis B (CHB) is unclear. This study was conducted in 29 treatment-naive patients undergoing telbivudine treatment for 52 weeks. The results showed that PD-1 expression on both CD4+ and CD8+ T cells was positively correlated with hepatitis B virus (HBV) DNA levels (r = 0.621, P

Air pollution is a risk factor for cardiovascular diseases (CVD), but the underlying biological mechanisms are not well understood.To determine whether markers related to CVD pathophysiological pathways (biomarkers for systemic inflammation and thrombosis, heart rate, and blood pressure) are sensitive to changes in air pollution.Using a quasi-experimental opportunity offered by greatly restricted air pollution emissions during the Beijing Olympics, we measured pollutants daily and the outcomes listed below in 125 healthy young adults before, during, and after the 2008 Olympics (June 2-October 30). We used linear mixed-effects models to estimate the improvement in outcome levels during the Olympics and the anticipated reversal of outcome levels after pollution controls ended to determine whether changes in outcome levels were associated with changes in pollutant concentrations.C-reactive protein (CRP), fibrinogen, von Willebrand factor, soluble CD40 ligand (sCD40L), soluble P-selectin (sCD62P) concentrations; white blood cell count (WBC); heart rate; and blood pressure.Concentrations of particulate and gaseous pollutants decreased substantially (-13% to -60%) from the pre-Olympic period to the during-Olympic period. Using 2-sided tests conducted at the .003 level, we observed statistically significant improvements in sCD62P levels by -34.0% (95% CI, -38.4% to -29.2%; P.001) from a pre-Olympic mean of 6.29 ng/mL to a during-Olympic mean of 4.16 ng/mL and von Willebrand factor by -13.1% (95% CI, -18.6% to -7.5%; P.001) from 106.4% to 92.6%. After adjustments for multiple comparisons, changes in the other outcomes were not statistically significant. In the post-Olympic period when pollutant concentrations increased, most outcomes approximated pre-Olympic levels, but only sCD62P and systolic blood pressure were significantly worsened from the during-Olympic period. The fraction of above-detection-limit values for CRP (percentage ≥ 0.3 mg/L) was reduced from 55% in the pre-Olympic period to 46% in the during-Olympic period and reduced further to 36% in the post-Olympic period. Interquartile range increases in pollutant concentrations were consistently associated with statistically significant increases in fibrinogen, von Willebrand factor, heart rate, sCD62P, and sCD40L concentrations.Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of inflammation and thrombosis and measures of cardiovascular physiology in healthy young persons. These findings are of uncertain clinical significance.

Background and Aims. Associations between air pollution and cardio-respiratory health have been well established; but direct human data to support biological mechanisms are limited. We investigated...

Study objectives: To validate the feasibility of the Hilbert–Huang transform (HHT) based cardiopulmonary coupling (CPC) technique in respiratory events detection and estimation of the severity of apnea/hypopnea. Methods: The HHT-CPC sleep spectrogram technique was applied to a total of 69 single-lead ECG signals downloaded from the Physionet Sleep Apnea Database. Sleep spectrograms generated by both the original and the improved CPC method were compared on the structure distribution and time–frequency resolution. The performance of respiratory events detection by using the power of low frequency coupling (pLFC) in the new method was estimated by receiver operating characteristic analysis. Furthermore, correlation between HHT-CPC index (temporal Variability of Dominant Frequency, TVDF) and conventional OSAHS scoring was computed. Results: The HHT-CPC spectrum provides much finer temporal resolution and frequency resolution (8 s and 0.001 Hz) compared with the original CPC (8.5 min and 0.004 Hz). The area under the ROC curve of pLFC was 0.79 in distinguishing respiratory events from normal breathing. Significant differences were found in TVDF among groups with different severities of OSAHS (normal, mild, moderate, and severe, p < 0.001). TVDF has a strong negative correlation with the apnea/hypopnea index (AHI, correlation coefficient � 0.71). Conclusions: The HHT-CPC spectrum could exhibit more detailed temporal-frequency information about cardiopulmonary coupling during sleep. As two spectrographic markers, pLFC and TVDF can be used to identify respiratory events and represent the disruption extent of sleep architecture in patients with sleep apnea/hypopnea, respectively. The proposed technique might serve as a complementary approach to enhance diagnostic efforts.

A facile and efficient method to differentiate the 2,3-diols of glucopyranosides based on 1,2-orthoesters strategy was developed. Stable thioglucosides were employed as the starting materials to prepare the corresponding 1,2-orthoesters. When treated with HCl aqueous solution and followed with Et 3 N, differentiation of the 2,3-diols was efficiently achieved along with the generation of a convertible anomeric hydroxyl group. In addition, an easy and practical method based on NOE was proposed to determine whether the 1,2-orthoesters were endo -type or exo -type.

The rare and expensive D-talose (V) is conveniently synthesized from readily available β-D-galactose pentaacetate (I).

The anti-inflammatory effect of methyl-1-hydroxy-2-naphthoate (MHNA), a novel naphthol derivative, was evaluated in the lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages. The release of nitric oxide (NO), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were detected by the Griess reagent and ELISA methods. The protein expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined by Western blotting. The mRNA expressions of IL-1β, IL-6, iNOS and COX-2 were determined by real-time PCR. Activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathways were detected by Western blotting, reporter gene assay and electrophoretic mobility shift assay. MHNA significantly inhibited the release of NO, IL-1β and IL-6 as well as the protein expression of iNOS and COX-2 in LPS-stimulated macrophages. It also inhibited the mRNA expression of iNOS, COX-2, IL-1β and IL-6. Further studies indicated that MHNA inhibited LPS-induced increases in NF-κB DNA-binding activity and NF-κB transcriptional activity as well as IκB-α degradation and NF-κB translocation in a dose-dependent manner. Meanwhile, the activation of p38 MAPK and c-Jun N-terminal kinases (JNK) induced by LPS were decreased by MHNA. MHNA inhibits the LPS-induced inflammatory response in murine macrophages via suppression of NF-κB and MAPKs signaling pathways activation.

Ambient air pollution has been linked to cardiovascular and respiratory morbidity and mortality in epidemiology studies. Frequently, oxidative and nitrosative stress are hypothesized to mediate these pollution effects, however precise mechanisms remain unclear. This paper describes the methodology for a major panel study to examine air pollution effects on these and other mechanistic pathways. The study took place during the drastic air pollution changes accompanying the 2008 Olympics in Beijing, China. After a general description of air pollution health effects, we provide a discussion of panel studies and describe the unique features of this study that make it likely to provide compelling results. This study should lead to a clearer and more precise definition of the role of oxidative and nitrosative stress, as well as other mechanisms, in determining acute morbidity and mortality from air pollution exposure.

Nine new alkyl 2,3-dihydroxybenzoates, gentisides C-K, were isolated from the traditional Chinese medicine Gentiana rigescens Franch. Their structures and stereochemistry were elucidated by spectroscopic methods, and comparison of the specific rotation with that of the gentiside B. These metabolites are additional members of the gentisides which belong to a novel class of neuritogenic compounds. They are structurally different from one another because they possess varying alkyl chain lengths, with or without an isobutyl or isopropyl group at the end of the alkyl chain. These compounds are potent inducers of neurite outgrowth on PC12 cells. The gentiside C possessing the shortest alkyl chain length exhibited the highest neuritogenic activity among all of the gentisides. Gentiside C showed a significant neuritogenic activity at 1 μM against PC12 cells comparable to that seen for the best nerve growth factor (NGF) concentration of 40 ng/mL. In addition, evident neuritogenic activity was observed in the cells when treated with gentiside C at a concentration as low as 0.03 μM. The structure-activity relationships within the gentisides A-K revealed that alkyl chain length is important for the activity, but structure diversity at the end of the alkyl chain is not.

Objectives: To evaluate the reliability and validity of the Chinese versions of Minnesota Nicotine Withdrawal Scale and Questionnaire on Smoking Urges-Brief (MNWS-C and QSU-Brief-C) in Chinese smokers. Design and methods: MNWS and QSU-Brief were translated into Chinese version through 10 steps. The reliability and validity of Chinese versions of the two scales were evaluated based on the data collected from 354 subjects. Cronbach's alpha coefficient was calculated to assess the reliability. Construct validity were evaluated with confirmatory factor analysis. Criteria validity was examined with correlation analysis between scale scores and patient-evaluated scores of craving and tobacco withdrawal symptoms. Results: Cronbach's alpha coefficient of QSU-Brief-C was .96. Confirmatory factor analysis demonstrated that the fit indexes (adjusted goodness-of-fit index [AGFI], comparative fit index [CFI], normed fit index [NFI], and non-normed fit index [NNFI]) exceeded or approached 0.9. The correlation between QSU-Brief-C scores and patient-evaluated craving scores were statistically significant(r = .75, p < .0001). Cronbach's alpha coefficient of MNWS-C was .90. Confirmatory factor analysis demonstrated that the fit indexes (AGFI, CFI, NFI, and NNFI) exceeded 0.9. The correlation between MNWS-C scores and patient-evaluated discomfort scores were statistically significant(r = .68, p < .0001). Conclusion: Both QSU-Brief-C and MNWS-C have satisfactory validity and reliability and retain the two dimensions identified in their corresponding original English versions, which suggest that QSU-Brief-C and MNWS-C can be used in further research and clinical evaluation in Chinese smoking population with acceptable validity and reliability.

We present a structured light system to dynami- cally measure human chest wall motion for respiratory volume estimation. Based on a projection of an encoded color pattern and a few active markers attached to the trunk, respiratory volumes are obtained by evaluating the 3-D topographic changes of the chest wall in an anatomi- cally consistent measuring region during respiration. Three measuring setups are established: a single-sided illuminating-recording setup for standing posture, an in- clined single-sided setup for supine posture, and a double- sided setup for standing posture. Results are compared with the pneumotachography and show good agreement in volume estimations correlation coefficient: R0.99 P0.001 for all setups. The isovolume tests present small variations of the obtained volume during the isovol- ume maneuver standard deviation0.085 L for all set- ups. After validation by the isovolume test, an investiga- tion of a patient with pleural effusion using the proposed method shows pulmonary functional differences between the diseased and the contralateral sides of the thorax, and subsequent improvement of this imbalance after drainage. These results demonstrate the proposed optical method is capable of not only whole respiratory volume evaluation with high accuracy, but also regional pulmonary function assessment in different chest wall behaviors, with the ad- vantage of whole-field measurement. © 2010 Society of Photo