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The flavor and aroma quality of green tea are closely related to the harvest season. The aim of this study was to identify the harvesting season of green tea by alcohol/salt-based aqueous two-phase system (ATPS) combined with chemometric analysis. In this paper, the single factor experiments (SFM) and response surface methodology (RSM) optimization were designed to investigate and select the optimal ATPS. A total of 180 green tea samples were studied in this work, including 86 spring tea and 94 autumn tea. After the active components in green tea samples were extracted by the optimal ethanol/(NH 4 ) 2 SO 4 ATPS, the qualitative and quantitative analysis was realized based on HPLC-DAD combined with alternating trilinear decomposition-assisted multivariate curve resolution (ATLD-MCR) algorithm, with satisfactory spiked recoveries (86.00 %-112.45 %). The quantitative results obtained from ATLD-MCR model were subjected to chemometric pattern recognition analysis. The constructed partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) models showed better results than the principal component analysis (PCA) model, and the R 2 X cum values (>0.835) and R 2 Y cum (>0.937) were close to 1, the Q 2 cum values were greater than 0.75 (>0.933), and the differences between R 2 Y cum and Q 2 cum were not larger than 0.2, indicating excellent cross-validation prediction performance of the models. Furthermore, the classification results based on the hierarchical clustering analysis (HCA) were consistent with the PCA, PLS-DA and OPLS-DA results, establishing a good correlation between tea active components and the harvesting seasons of green tea. Overall, the combination of ATPS and chemometric methods is accurate, sensitive, fast and reliable for the qualitative and quantitative determination of tea active components, providing guidance for the quality control of green tea., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults., Methods: Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection., Results: All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed., Conclusion: The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Aim: To determine whether Houttuynia cordata Thunb (HCT) can increase the survival of the retinal ganglion cells (RGCs) and inhibit microglia activation following retinal ischemia-reperfusion (RIR) injury., Methods: Rat model of RIR was induced by transient elevation of the intraocular pressure (IOP). HCT was orally administered for 2d before the performance of retinal RIR model and once a day for the next 14d. After 14d of RIR injury, the rats were sacrificed for further analysis. Survival RGCs were stained with haematoxylin and eosin (H&E). Apoptosis of RGCs was detected by TUNEL staining. Retinal function was examined by flash-electroretinography (F-ERG). Retinal microglia were labeled using Iba-1, one specific marker for microglia. The mRNA expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were assessed by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR)., Results: Systemic HCT treatment significantly reduced RGCs death by H&E staining and exhibited an anti-apoptotic effect as assessed by TUNEL staining at day 14 after RIR injury. HCT greatly improved the retinal function as examined by F-ERG. The number of activated microglia significantly increased after RIR injury, which was significantly attenuated by HCT treatment. Besides, RIR injury induced a strong upregulation of pro-inflammatory genes TNF-α, iNOS and IL-1β mRNAs at day 14 post injury, which was suppressed by HCT., Conclusion: Neuroprotective effects of HCT encourage the survival of RGCs through inhibiting microglia activation due to RIR injury. Together these results support the use of HCT as promising therapy for the ischemic events of the retina diseases., (International Journal of Ophthalmology Press.)

This study aims to compare the expression of P2X receptor subtype mRNA in different arterial tissues of rats. After the rats were sacrificed, the internal carotid, pulmonary, thoracic aorta, mesenteric and caudal arteries were dissected out. Then, the P2X receptor mRNA expression in different blood vessels was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative polymerase chain reaction. The P2X1, P2X4 and P2X7 receptor mRNA amplification products revealed specific bands of the same size as the amplified target fragment in their respective lanes, while the P2X2, P2X3, P2X5 and P2X6 receptor mRNA amplification products did not reveal significant specific bands in their respective lanes by RT-PCR. Based on the P2X1 receptor mRNA expression of the mesenteric artery, there were no significant differences in the internal carotid, pulmonary and thoracic aorta (0.64 ± 0.07, 0.17 ± 0.11 and 1.49 ± 0.65, respectively). However, the P2X1 receptor mRNA expression level in the caudal artery significantly increased (11.06 ± 1.99, P < 0.01). Furthermore, there was no difference in P2X4 receptor mRNA expression among these five blood vessels (P > 0.05). The P2X7 receptor mRNA expression level was significantly different: pulmonary artery < tail artery = thoracic aorta < internal carotid artery < mesenteric artery. The relative P2X1 receptor mRNA expression in the caudal artery was observed to be elevated when compared to that of the internal carotid, pulmonary and thoracic aorta as well as the mesenteric arteries. The P2X7 receptor mRNA expression level is pulmonary artery < caudal artery = thoracic aorta < internal carotid artery < mesenteric artery. P2X4 receptor mRNA expression was not significantly different among these five blood vessels.

Objective: To summarize the clinical characteristics of patients misdiagnosed with IgG4-related disease, to analyze the reasons of misdiagnosis and to improve the clinical recognition of the disease., Methods: The general data, clinical manifestations, laboratory examination results and pathological features of 17 patients with IgG4-related diseases misdiagnosed outside the hospital were retrospectively analyzed., Results: Among the 17 patients, there were 9 males and 8 females with a median age of 45 years, and the median time from onset to diagnosis was 12 months. Most patients' initial admission department was not rheumatology or immunology department. Six of the 17 patients were eventually diagnosed with lymphoproliferative disease, 4 with autoimmune disease, and 2 with infectious disease, Rosai Doffman disease, desmofibromatosis, highly differentiated mucoepidermoid carcinoma of the bottom of the mouth, hypereosinophilic syndrome, asthma and allergic rhinitis in 1 case each. The typical sites of IgG4-related disease were involved in 14 patients, including 6 cases of parotid gland, 2 cases of submandibular gland, 3 cases of pancreas and 2 cases of retroperitoneal lesions. Serum IgG4 was elevated in 10 patients, serum IgG4/IgG value was higher than 10% in 7 patients, serum IgE was increased in 7 patients, complement was decreased in 4 patients, and eosinophilic granulocytes were increased in 3 patients. Pathological biopsy was performed in 15 patients, and infiltration of lymphocyte was observed in 10 patients, IgG4+ plasma cells were present in 5 patients, the ratio of IgG4+ plasma cells to IgG+ plasma cells was less than 40% in 4 patients and greater than 40% in 1 patient. However, none of the 15 patients had the storiform pattern of fibrosis and obliterative phlebitis., Conclusion: A variety of diseases can perform as IgG4-related disease witih typical sites involved, elevated serum IgG4, even can be characterized by pathological IgG4+ plasma cells infiltration. Physicians should pay attention to the differential diagnosis and comprehensively evaluate the patient's clinical manifestations, and laboratory results. Timely and even repeated pathological biopsy is also needed for definite diagnosis.

The electro-Fenton (EF) process was applied to treat mother liquor of gas field wastewater (ML-GFW). The Fe-Fe electrodes were used and H 2 O 2 was added to the EF system. Effect of initial pH on chemical oxygen demand (COD) removal efficiency, specific electrical energy consumption (SEEC), specific electrode plate consumption (SEPC) and organic matter removal mechanism was investigated. The results showed that COD removal efficiency reached the maximum (71.9%) at initial pH of 3 after reaction for 3 h. Besides, considering with the SEEC and SEPC, pH of 3 was also the best choice, at which SEEC was 4.7 kW h kg COD -1 , SEPC was 0.82 kgFe kg COD -1 . Organic matter removal was achieved by two ways: oxidation and flocculation, and oxidation played a major role. With the analysis of GC-MS, the possible degradation pathways of the representative contaminants in the ML-GFW were given., Competing Interests: We declare we have no competing interests., (© 2019 The Authors.)

Biological control is an effective method for whitefly management compared to the potential problems caused by chemical control, including environmental pollution and the development of resistance. Combined use of insect parasitoids and entomopathogenic fungi has shown high efficiency in Bemisia tabaci control. Here, we assessed the impacts of an entomopathogenic fungus, Cordyceps javanica, on the parasitism rate of a dominant whitefly parasitoid, Eretmocerus hayati , and for the first time also compared their separate and combined potential in the suppression of B. tabaci under semi-field conditions. Six conidial concentrations of C. javanica (1 × 10 3 , 1 × 10 4 , 1 × 10 5 , 1 × 10 6 , 1 × 10 7 and 1 × 10 8 conidia/mL) were used to assess its pathogenicity to the pupae and adults of E. hayati . Results showed that the mortality of E. hayati increased with higher concentrations of C. javanica , but these higher concentrations of fungus had low pathogenicity to both the E. hayati pupae (2.00-28.00% mortality) and adults (2.67-34.00% mortality) relative to their pathogenicity to B. tabaci nymphs (33.33-92.68%). Bioassay results indicated that C. javanica was harmless (LC 50 = 3.91 × 10 10 ) and slightly harmful (LC 50 = 5.56 × 10 9 ) to the pupae and adults of E. hayati respectively on the basis of IOBC criteria, and that E. hayati could parasitize all nymphal instars of B. tabaci that were pretreated with C. javanica , with its rate of parasitism being highest on second-instar nymphs (62.03%). Interestingly, the parasitoids from second and third-instar B. tabaci nymphs infected with C. javanica had progeny with increased longevity and developmental periods. Moreover, experimental data from 15 day semi-field studies indicate that combined application of C. javanica and E. hayati suppresses B. tabaci with higher efficiency than individual applications of both agents. Therefore, combined applications of C. javanica (1 × 10 8 conidia/mL) and E. hayati is a more effective and compatible biological control strategy for management of B. tabaci than using either of them individually.

Aim: To identify the effect of Houttuynia cordata Thunb (HCT) on lipopolysaccharide (LPS)-induced microglial activation and investigate its possible molecular mechanisms., Methods: The primary retinal microglial cells were cultured from the retinas of newborn Sprague-Dawley rats and exposed to LPS, and/or HCT with different concentrations. The survival ability of retinal microglia cells was tested by standard MTT method. BrdU cell proliferation assay was used to evaluate the proliferation of retinal microglia. Inflammatory factors in the culture supernatants, including TNF-α, iNOS and IL-1β, were measured using ELISA. Microglia cells' migration was determined with Transwell migration assay. The total p38-MAPK and phosphorylation of p38-MAPK (p-p38-MAPK) were detected with Western blot., Results: Primary retinal microglia in culture exposed to LPS to induce microglia activation. Pretreatment with HCT significantly inhibited the LPS-induced cell proliferation, but not the cell viability. LPS induced inflammatory reaction in microglia and cell migration. HCT significantly reduced LPS-stimulated release of pro-inflammatory factors and decreased the number of migrating cells substantially in a concentration-dependent manner. Moreover, the protein levels of p-p38 MAPK were identified as the up regulation and co-treatment with HCT obviously inhibited the upregulation of p-p38 MAPK, but had no effect on the levels of total p38-MAPK., Conclusion: The data suggest that HCT inhibits LPS-induced retinal microglial activation via suppression of the p-p38-MAPK. HCT may be used for the treatment of ocular diseases characterized by over-activated microglia.

Objective: To analyze the 20-year survival rate, causes of death and predictors of systemic lupus erythematosus (SLE). Methods: A retrospective analysis was performed on 217 newly SLE patients who were diagnosed and treated by Peking University People's Hospital before June 2008. The clinical features and serologic data were studied. Survival rate of SLE patients over time, living conditions, causes of death and prognostic indicators of mortality were studied. Results: The 10-, 15-and 20-year cumulative survival rate was 90.3%,88.1%and 79.6%, respectively. Infection and lupus encephalopathy were the main causes of death. Cox regression analysis revealed that lupus nephritis, neuropsychiatric systemic lupus erythematosus and age at the diagnosis were independent risk determinants for mortality. Conclusion: Prognosis of SLE remains to be improved. Early diagnosis, control of SLE organ damage and infection prevention are critical to improve survival of SLE patients.

Objective: To comprehend clinical features and patient's physician visit patterns at onset of immunoglobulin G4 related disease (IgG4RD)., Methods: In the study, 100 patients with IgG4RD who received treatments in the Department of Rheumatology and Immunology of Peking University People's Hospital from Apr. 1st, 2017 to Apr. 1st, 2018 were investigated, including gender, age, height, body weight, age of onset, physician visit history, primary history and how did the disease affected their life, etc. RESULTS: In this 100 IgG4RD cohort (57 males and 43 females), the male/female ratio was 1:0.75, the mean age of onset was (51.51±12.9) years, and the median duration was 49 months (ranging from 4 to 231 months). The onset age of males was significantly older than that of females (P<0.01). The manifestations showed that up to 69% patients had submaxillay glands lesion, 59% patients had lacrimal glands lesion, 28% patients had pancreas involvement and 28% patients had parotid glands involvement. The females had more lacrimal glands involvement (P<0.05). 62% patients were complicated with anaphylactic disease. The primary physician visit departments concentrated upon general surgery department (19/100), oral and maxillofacial surgery department (17/100), rheumatology and immunology department (16/100), ophthalmology department (15/100) and gastroenterology department (10/100). The departments where the confirmed diagnose was made concentrated upon rheumatology department (67/100),oral and maxillofacial surgery department (16/100) and gastroenterology department (7/100). The mean diagnosis duration after 2010 was (16.96±2.163) months, significantly shorter than that before 2010, which was (113.3±11.01) months. Before the definite diagnose was made, 43% patients underwent surgeries and 12% patients had more than one time surgeries. The patients whose first-visit department was a surgery department were more likely to undergo surgeries (P<0.01). 18% patients (18/100) stated that the disease had affected their work., Conclusion: In this cohort of the IgG4RD patients, female is common and has earlier onset age than male. The major manifestations of IgG4RD are salivary glands, lacrimal glands and pancreas involvement. The common chief complains are salivary glands and lacrimal glands enlargement. Accompanied by anaphylactic disease is a marked manifestation of this disease. Delayed diagnoses are not rare, though this situation has been improved since 2010, and more attention still should be paid to the disease.

Background: Bupivacaine induces central neurotoxicity at lower blood concentrations than cardiovascular toxicity. However, central sensitivity to bupivacaine is poorly understood. The toxicity mechanism might be related to glutamate-induced excitotoxicity in hippocampal cells., Methods: The intracellular free Ca concentration ([Ca]i), mitochondrial membrane potential, and reactive oxygen species generation were measured by fluorescence and two-photon laser scanning microscopy in fetal rat hippocampal neurons and astrocytes., Results: In astrocyte/neuron cocultures, 300 μM bupivacaine inhibited glutamate-induced increases in [Ca]i in astrocytes by 40% (P < 0.0001; n = 20) but significantly potentiated glutamate-induced increases in [Ca]i in neurons by 102% (P = 0.0007; n = 10). Ropivacaine produced concentration-dependent effects similar to bupivacaine (0.3 to 300 μM). Tetrodotoxin did not mimic bupivacaine's effects. In pure cell cultures, bupivacaine did not affect glutamate-induced increases in [Ca]i in neurons but did inhibit increased [Ca]i in astrocytes. Moreover, bupivacaine produced a 61% decrease in the mitochondrial membrane potential (n = 20) and a 130% increase in reactive oxygen species generation (n = 15) in astrocytes. Cyclosporin A treatment suppressed bupivacaine's effects on [Ca]i, mitochondrial membrane potential, and reactive oxygen species generation. When astrocyte/neuron cocultures were incubated with 500 μM dihydrokainic acid (a specific glutamate transporter-1 inhibitor), bupivacaine did not potentiate glutamate-induced increases in [Ca]i in neurons but still inhibited glutamate-induced increases in [Ca]i in astrocytes., Conclusions: In primary rat hippocampal astrocyte and neuron cocultures, clinically relevant concentrations of bupivacaine selectively impair astrocytic mitochondrial function, thereby suppressing glutamate uptake, which indirectly potentiates glutamate-induced increases in [Ca]i in neurons.

Background: Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic disease. Despite its good response to steroid therapy, its treatment protocol is not standardized and the long-term outcome is controversial. The study was conducted to determine the short-term and long-term outcomes of IgG4-RS patients treated with glucocorticoids and steroid-sparing immunosuppressive agents, to analyze secretory function, serological and radiological changes in salivary glands and to assess the usefulness of serum IgG4 level as an indicator of disease activity., Methods: IgG4-RS patients who were treated for more than 3 months were enrolled. Serological tests, salivary gland function assessment and computed tomography (CT) were performed before treatment and during follow up. The treatment outcomes in the short and the long term were evaluated, and the relationship between serum IgG4 level and salivary gland volume was analyzed., Results: Glucocorticoids were used in all 43 patients and steroid-sparing immunosuppressive agents in 38 patients (88.4%). The follow-up period was 24.6 ± 14.9 months. Clinical remission was achieved in all patients after induction therapy. During short-term observation, salivary gland secretion significantly increased, and the serum IgG4 levels, the volumes and CT values of submandibular and parotid gland decreased significantly (P < 0.001). For long term, relapse occurred in 32.5% patients within 55 months in the regularly treated group, while all seven irregularly treated patients relapsed. However, the relapse-free survival curves were not significantly different between the steroid monotherapy and the combination therapy groups (P = 0.566). Submandibular glands, lacrimal glands, sublingual glands, nasal and paranasal cavity were commonly relapsing organs. In clinically stable patients, a serologically unstable condition occurred in 54.9% patients within 55 months and medication adjustment was performed accordingly. Volume changes in the submandibular and parotid glands were associated with serum IgG4 levels and time of follow up (R 2 adjusted  = 0.905, P < 0.0001 and R 2 adjusted  = 0.9334, P < 0.0001, respectively)., Conclusions: The combination of glucocorticoid and steroid-sparing agents could be effective for treating IgG4-RS, and restoring salivary gland function. Serum IgG4 levels could predict disease activity.

Our aim was to differentiate IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis by analysing clinical, radiographic, and pathological features. Fifty-five patients, 50, and 50 were enrolled, respectively and their baseline characteristics and serological, sialographic, and pathological findings compared. The male:female ratio for IgG4-related sialadenitis was 1:1.2 for primary Sjögren syndrome 1:15.7, and for chronic obstructive submandibular sialadenitis1:0.92. Numbers with enlarged salivary glands were 55, 16, and 50; with xerostomia 26, 48, and 0; with a history of allergy 26, 4, and 6, and with coexisting systemic disease 12, 19, and 0 (p=0.14). Mean (SD) serum IgG4 concentrations were 109.1 (97.9), 4.9. (1.9) g/L, and 5.3 (1.6) g/L, p<0.001 in all cases. Sialography showed enlargement of the gland, dilatation of the duct, and slightly decreased secretory function in IgG4-related disease; obvious sialectasia and decreased secretory function in Sjögren syndrome; and dilatation of Wharton's duct and filling defects in obstructive sialadenitis. Histopathological examination showed lymphoplasmacytic infiltration with storiform fibrosis, lymphoplasmacytic inflammation and lymphoepithelial lesions, and dilatation of the duct with epithelial metaplasia in the three groups, respectively. The number of IgG4-positive plasma cells was 123 (45)/HPF, 8 (3)/HPF, and 5 (4)/HPF, while the IgG4-/IgG-positive cell ratio was 71.7 (13.9)%, 4.6 (2.5)%, 18.9 (19.7)%, respectively (p<0.001). The three conditions have different clinical, radiographic, and pathological features that provide important clues to the differential diagnosis. Serological and histological tests are important, and comprehensive consideration is necessary., (Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Iron nanoparticles are widely used in heavy metal ions removal from water, but because of the characteristics of easily aggregation and transference in the groundwater, remediation effect was reduced. GO with a negative charge containing oxygen-containing functional groups on the surfaces of graphene, are widely used for the removal of heavy metal ions from water, but it has little on remediating hexavalent chromium (Cr2O2-7, CrO2-4) with negatively charged electrons. Therefore, rGO-nZⅥ was synthesized via liquid phase reduction method to overcome the aggregation and transference of FeO, changing the negative charged Cr2O2-7 or CrO2-4 to positive charged Cr3+. The material behavior characteristics of Cr(Ⅵ) removal were discussed. X-ray diffraction (XRD) and transmission electron microscopy (TEM) were used to test the prepared rGO-nZⅥ. Results indicated that nZⅥ was successfully loaded on the surface of GO, and the shape of the particles was approximate ball and the granular diameter ranged from 20 to 100 nm. Removal efficiency of Cr(Ⅵ) (40 mg·L-1) from water was nearly 100% within 24 h using rGO-nZⅥ. X-ray photoelectron spectroscopy (XPS) analyses using the XPSPEAK41 program indicated that FeO firstly reduced negatively charged Cr(Ⅵ) to positively charged Cr(Ⅲ) by providing electron, then the chromium in the solution can be removed as chromium hydroxide (Cr(OH)3) by a hydrolysis precipitation process. As the reaction progress, materials charges were changing, which benefited adsorpting Cr(Ⅵ). After 24 h reaction, the residual nZⅥ loading on rGO-nZⅥ remained, which showed the potential of sequentially remediating contamination. The results showed important theoretical value and practicability.

Objective: To retrospectively investigate the clinical characteristics, risk factors of Cytomegalovirus (CMV) infection in patients with underlying rheumatic diseases. Methods: Clinical records of 263 rheumatic patients with or without CMV infection, hospitalized from March 2011 to June 2014 in Peking University People's Hospital, were analyzed.Clinical characteristics were summarized and compared in CMV positive and negative groups, to investigate the risk factors for CMV infection.Statistical analyses were conducted with SPSS 20.0 software. Results: A total of 62 rheumatic patients were found to have CMV infection, with 48 regarded as CMV viremia, 7 diagnosed as CMV pneumonia, while the remaining 7 suffered both CMV viremia and pneumonia.Eleven of 62 patients (17.7%) had a fatal outcome.Systemic lupus erythematosus (SLE) was the most commonly underlying disease (41.9%), followed by Sjögren syndrome (16.1%) and systemic vasculitis (12.9%). Lymphopenia and the reduction of CD4 + T lymphocytes, corticosteroids, cyclophosphamide (CTX) or mycophenolate mofetil (MMF), combined use of more than 2 immunosuppressants and other severe underlying infections as risk factors for CMV infection in rheumatic patients.Meanwhile, the total dose of CTX wasn't different significantly between CMV positive and negative groups.Multivariate analysis revealed that large or pulsed dose of corticosteroids, combined use of immunosuppressants, and severe underlying infections remained independent risk factors for CMV infection. Conclusions: Lymphocytes, particularly the CD4 + T subsets, might play a vital role in the regulation and control of CMV infection.Other underlying infections, undergoing large dose corticosteroids therapy or combined use of immunosuppressants could be the risk factors for CMV infection in rheumatic patients.

Previous publications showed that the value of LLOQ (lowest limit of quantification) for doxazosin and its enantiomers in biological samples were above 0.1 ng·m L(-1). The present study was designed to establish a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification at very low concentration of (-)doxazosin in rat plasma after intravenous administration of (-)doxazosin（3.0 mg·kg(-1)）. The plasma samples containing prazosin as an internal standard were extracted by solid-phase extraction (SPE) and separated on Acquity BEH C(18) (50 mm × 2.1 mm, 1.7 μm) column under alkaline conditions of the mobile phase. (-)Doxazosin was monitored under positive ionization condition by multiple reaction monitoring (MRM) with an ESI source. The good linear range of (-)doxazosin varied from 10.4 pg·m L(-1) to 13 ng·m L(-1)（r = 0.992 2), and the lowest limit of quantification was 10.4 pg·m L(-1). An assessment of the matrix effect using post-extraction spiking method and post-column infusion method demonstrated that co-eluting matrix components did not significantly influenced the ionization of (-)doxazosin and prazosin (IS). Using the new method, we accurately measured (-)doxazosin concentration at 48 h after intravenous administration in the rats, and the concentration was 0.034 4 ± 0.010 2 ng·m L(-1). The method is specific, sensitive, and suitable for determining (-)doxazosin at very low concentration in rat plasma samples.

Aim: The aim of this study was to determine the efficacy and safety of a weekly dose of leflunomide (50 mg/week) in early rheumatoid arthritis patients with mild or moderate disease activity., Methods: The patients of early rheumatoid arthritis (ERA) with mild or moderate disease activity were randomly selected for inclusion in this study and were assigned to either the treatment group (leflunomide 50 mg/week, LEF50) or the control group (leflunomide 10 mg/day, LEF10). All patients were treated for 24 weeks. Clinical efficacy was assessed using the disease activity score in 28 joints (DAS28) - erythrocyte sedimentation rate (ESR) and European League Against Rheumatism (EULAR) response. A Chi-squared test, Fisher's exact-test and paired t-tests were used to analyze the data., Results: A total of 244 patients who met the inclusion criteria and received at least one medicine dose were analyzed. At the baseline, the DAS28 (ESR) of the ERA patients were 4.41 ± 0.69 in LEF 50 group and 4.52 ± 0.64 in LEF 10 group, respectively. At week 24, the DAS28 (ESR) in two groups ( 2.94 ± 1.10 and 3.02 ± 1.14 ) were significant decreased compare with the baseline, respectively (P<0.01). There was no significant difference in DAS28 (ESR) between the LEF50 and LEF10 groups at week 24. (P > 0.05). At weeks 8, 12 and 24, the EULAR response (good responses + moderate responses) were 47.6%, 58.7% and 59.5%, in the LEF50 group and 43.2%, 49.1% and 53.4% in the LEF10 group, respectively. There was no significant different of EULAR response rates in the two groups at week 8, 12, and 24, respectively (P>0.05). There was no serious adverse events during the study., Conclusion: A weekly dose of 50 mg leflunomide showed similar benefits to a daily dose of 10 mg leflunomide for the treatment of mild-to-moderate early rheumatoid arthritis., (© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

To investigate apoptosis mechanisms in lymphocytes induced by aluminum trichloride (AlCl3) through the mitochondria-caspase dependent pathway, the spleen lymphocytes of rats were cultured with RPMI-1640 medium and exposed to AlCl3·6H2O in the final concentrations of 0 (control group, CG), 0.3 (low-dose group, LG), 0.6 (mid-dose group, MG), and 1.2 (high-dose group, HG) mmol·L(-1) for 24 h, respectively. Mitochondrial transmembrane potential (ΔΨm), cytochrome C (Cyt C) protein expression in cytoplasm, Caspase-3 and Caspase-9 activity, Bcl-2, Bax, Caspase-3 and Caspase-9 mRNA expressions, DNA ladder and lymphocytes apoptosis index were detected. The results showed that Cyt C protein expression in cytoplasm, Caspase-3 and Caspase-9 activity, Bcl-2, Bax, Caspase-3 and Caspase-9 mRNA expressions, the ratio of Bcl-2 and Bax mRNA expression, lymphocytes apoptosis index increased, while ΔΨm decreased in the AlCl3-treated groups compared with those in CG. The results indicate that AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway., (© 2014 Wiley Periodicals, Inc.)

Objective: To observe the effect of salidroside on tic behavior and in vivo dopamine DA) and serotonin (5-HT) levels in Tourette syndrome (TS) model rats., Methods: Forty rats were randomly divided into the blank control group, the TS model group, the haloperidol-treated group (0.5 mg/kg x d(-1)), and the salidroside-treated group (50 mg/kg x d(-1)), 10 in each group. TS rat model was induced by imino-dipropio-nitrile (IDPN). Peritoneal injection of haloperidol and salidroside was started from the 4th day of modeling in the haloperidol-treated group and the salidroside-treated group respectively. Normal saline was peritoneally injected to rats in the blank control group and the TS model group respectively. Stereotyped behavior was scored, and changes of DA and 5-HT levels in blood and striatum were measured before modeling, after modeling, and after intervention., Results: Compared with the blank control group, the score of the tic behavior was elevated (P < 0.01) , levels of DA and 5-HT in plasma and striatum were reduced in the model group (P < 0.01, P < 0.05). Compared with the same group after modeling, the tic behavior score decreased and plasma DA levels increased in the two treated groups after intervention (P < 0.01). 5-HT content increased in the salidroside-treated group (P < 0.01). Compared with the model group after intervention, the tic behavior score was significantly reduced (P < 0.01), and DA levels in plasma and striatum were elevated (P < 0.01, P < 0.05) in the salidroside-treated group and the haloperidol-treated group. Compared with the haloperidol-treated group, the tic behavior score increased (P < 0.01), DA levels in plasma and striatum were lowered (P < 0.01, P < 0.05), the 5-HT level increased in plasma and striatum (P < 0.01, P < 0.05) in the salidroside-treated group., Conclusions: In the salidroside-treated group, the tic behavior was significantly reduced, and DA levels in plasma and striatum were elevated. Its mechanism might be related to regulating activities of dopamine neurons in striatum.

Aim: Arterial function is significantly influenced by bupivacaine at both clinically relevant concentrations and toxic concentrations, but the underlying mechanisms are not fully understood. In the present study we investigated the role of α1-adrenoceptors in bupivacaine effects on isolated rat aortas., Methods: Isolated aortic rings were prepared from rats and suspended in an organ bath. Phenylephrine (Phe)-induced vasoconstriction and acetylcholine (ACh)-induced vasodilation were recorded through an isometric force transducer connected to a data acquisition system., Results: Administration of bupivacaine (30-300 μmol/L) produced mild vasoconstriction, and this response declined with repeated administrations. Treatment of the aortic rings with bupivacaine (3-30 μmol/L) for 20 min enhanced Phe-induced vasoconstriction, while treatment for 40 min suppressed Phe-induced vasoconstriction. Both the short- and long-term bupivacaine treatment suppressed ACh-induced vasodilation. Incubation of the aortic rings with 0.2%-0.6% lipid emulsion (LE) for 100 min significantly increased the pD2 and Emax values of Phe-induced vasoconstriction, and incubation with 0.4% LE for 100 min reversed the inhibition of bupivacaine on vasoconstriction induced by Phe (30 μmol/L). In contrast, incubation with LE suppressed ACh-induced vasodilation, even at a lower concentration and with a 5-min incubation., Conclusion: Bupivacaine exerts dual effects on α1-adrenoceptor-mediated vasoconstriction of isolated rat aortic rings: short-term treatment enhances the response, while long-term treatment inhibits it; the inhibition may be reversed via long-term incubation with LE.

The aims of this study were to examine the effects of doxazosin on contractile responses to 5-hydroxytryptamine (5-HT), carbachol, and histamine, and to compare them with those of prazosin, alfuzosin, and terazosin, and then characterize a pharmacological profile of the 5-HT-induced contractile response using preparations of isolated longitudinal muscle strips from the rabbit gastric body. The results from these preparations showed that the contraction response to 5-HT, but not to carbachol or histamine, was found to be dose-dependently potentiated by doxazosin and its enantiomers. The specific potentiation effect on 5-HT was not observed in the preparations that were treated with prazosin, terazosin, or alfuzosin. The contractile response to 5-HT and its potentiation by doxazosin were not affected by treatment with phenoxybenzamine. However, 5-HT-induced contraction was competitively antagonized by nefazodone (with pA₂ value of 8.64 ± 0.17), and was almost completely inhibited by treatment with indomethacin. In conclusion, doxazosin, but not prazosin, alfuzosin, or terazosin, selectively potentiates 5-HT-induced contraction in the rabbit gastric body strips via an α₁-adrenoceptor-independent mechanism, without chiral recognition of its enantiomers. Additionally, the contraction to 5-HT was found to be mediated via 5-HT(₂) receptors, and was similar to PGs synthesis in the preparations.

Traditional medicine (herb medicine) began to prevail again over last two decades, and it is about 70% of the world population taking herb medicine as supplement or alternative medicine according to a recent survey. The consumption of herb medicine increased exponentially in Canada, Australia and Europe during last 10 years. Since concomitant administration of herbal and western medicine has become a trend, it requires paying close attention to the problem. Herb-drug interactions have been extensively investigated worldwide, and there is an increasing concern about the clinical herb-drug interaction. In this review we introduced the current progress in the herb-drug interactions including evidence-based clinical studies and establishment of levels of evidence for herb-drug interaction; and in the related mechanisms including the induction and inhibition of metabolic enzymes, inhibition and induction of transport and efflux proteins, alteration of gastrointestinal functions, and alteration in renal elimination. We also analyzed both the achievements and the challenges faced in the concomitant administration of traditional Chinese medicine and western medicine.

Aim: Doxazosin is a racemic mixture of (-)doxazosin and (+)doxazosin that is currently used as an add-on therapy for hypertension. In this study we investigated the contribution of each enantiomer to the hypotensive action of long-term administration of (±)doxazosin in conscious rats., Methods: Blood pressure of conscious SD rats was measured using a volume pressure recording system. The rats were orally administered (-)doxazosin, (+)doxazosin, or (±)doxazosin (8 mg·kg(-1)·d(-1)) for 12 weeks. Plasma concentrations of the agents were analyzed with HPLC. The effect of the agents on α1-adrenoceptor was examined in isolated rat caudal artery preparations., Results: Treatment of conscious rats with a single dose of (±)doxazosin (8 mg/kg) did not affected DBP and MBP, but significantly decreased SBP by 11.9% 4 h after the administration. Long-term treatment of conscious rats with (±)doxazosin significantly decreased SBP, DBP and MBP with a maximal decrease of SBP by 29.3% 8 h after the last administration. The rank order of the hypotensive actions caused by long-term treatment in conscious rats was (±)doxazosin>(+)doxazosin>>(-)doxazosin. However, the pKB values for inhibiting NA-induced contraction of isolated rat caudal artery were (+)doxazosin (8.995)>(±)doxazosin (8.694)>(-)doxazosin (8.032). The plasma concentrations of (-)doxazosin, (+)doxazosin, and (±)doxazosin were 18.26±3.55, 177.11±20.66, and 113.18±13.21 ng/mL, respectively, 8 h after the last administration of these agents., Conclusion: Long-term treatment with (±)doxazosin produces potent hypotensive action in conscious rats that seems to result from synergic interaction of the two enantiomers.

Ethnopharmacological Relevance: Coptidis Rhizoma has been used to treat diabetes mellitus for more than 1400 years in China. Berberine, one of the main alkaloids of Coptidis Rhizoma, is a principal antidiabetic component of Coptidis Rhizoma. To investigate the effects of berberine on impaired neurogenic contractility of detrusor muscle from urinary bladder of rats with early stage diabetes., Materials and Methods: The detrusor muscle strips were isolated from urinary bladders of streptozotocin-induced diabetic rats, 5% sucrose-induced diuretic rats or normal rats, and were placed in organ bath. The contractions induced by electrical field stimulation (EFS), carbachol, KCl, adenosine triphosphate, and the effects of berberine on those contractions were measured., Results: The EFS- or KCl-induced contraction of detrusor muscle was significantly decreased in diabetic rats as compared with diuretic or normal rats. Atropine and suramin inhibited EFS-induced contraction. In diabetic rats, the atropine sensitive components were decreased in EFS-induced contraction of detrusor muscle, and the adenosine triphosphate-induced contraction was significantly increased. The carbachol-induced contrations were not different among groups. Berberine significantly potentiated EFS-induced contractions of detrusor muscle both from normal and diabetic rats, but the potentiated effect of BBR was more sensitive to atropine in diabetic rats. Berberine also potentiated adenosine triphosphate-induced contraction of detrusor muscle, but did not change carbachol- or KCl-induced contraction., Conclusion: The neurogenic contraction of urinary bladder detrusor muscle is decreased while purinergic contraction of bladder detrusor muscle is increased in rats with early stage diabetes. Berberine increases the neurogenic contractile response to EFS possibly via both presynaptic increasing neurotransmitters release and postsynaptic potentiation of purinergic transmitter-regulated response in rat urinary bladder detrusor; and in diabetic rats, berberine increases neurogenic contractile response mainly via the presynaptic increasing acetylcholine release., (© 2013 Published by Elsevier Ireland Ltd.)

Aim: (±)Doxazosin is a long-lasting inhibitor of α1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro., Methods: Human, dog and rat plasma were prepared. Equilibrium dialysis was used to determine the plasma protein binding of each enantiomer in vitro. Chiral HPLC with fluorescence detection was used to measure the drug concentrations on each side of the dialysis membrane bag., Results: Both the enantiomers were highly bound to the plasma proteins of rats, dogs and humans [(-)doxazosin: 89.4%-94.3%; (+)doxazosin: 90.9%-95.4%]. (+)Doxazosin exhibited significantly higher protein binding capacities than (-)doxazosin in all the three species, and the difference in the bound concentration (Cb) between the two enantiomers was enhanced as their concentrations were increased. Although the percentage of the plasma protein binding in the dog plasma was significantly lower than that in the human plasma at 400 and 800 ng/mL, the corrected percentage of plasma protein binding was dog>human>rat., Conclusion: (-)Doxazosin and (+)doxazosin show stereoselective plasma protein binding with a significant species difference among rats, dogs and humans.

The study is to establish an HPLC method using fluorescence detector for the determination of doxazosin enantiomers and investigate their chiral inversion in vitro and in vivo. Ultron ES-OVM was taken as the chiral chromatographic column, and the column temperature was 30 degrees C. Isocratic elution using a mobile phase of phosphate buffer-acetonitrile (85 : 15, v/v) at a flow rate of 0.8 mL x min(-1) was done. The fluorescence detection was set at lambda(Ex) = 255 nm and lambda(Em) = 385 nm. Prazosin was used as the internal standard. (-) Doxazosin or (+) doxazosin added into rat plasma in vitro was determined after incubating in 37 degrees C water bath for 2, 5 and 10 days. (-) Doxazosin or (+) doxazosin was administered orally to the rats for one months. Plasma samples were taken at 8 h after the last administration. A good linear relationship was achieved when the concentration of doxazosin enantiomers was within the range of 4 - 2 000 ng x mL(-1). The average recovery for (-) doxazosin was 99.5% with RSD 3.6%, and for (+) doxazosin was 99.3% with RSD 4.3%. Chiral inversion was observed neither in vitro nor in vivo studies. The method is selective, accurate and reproducible, which is suitable for the detection of doxazosin enantiomers in rat plasma. The in vitro and in vivo studies indicate that chiral inversion occurs uneasily between (-) doxazosin and (+) doxazosin in the rat.

Doxazosin used in benign prostatic hyperplasia has the side effects of causing hypotension and the risk of heart failure. The 3 targets of α(1A)-adrenoceptors (in the prostate), α(1D)-adrenoceptors (in the aorta), and an unknown mechanism (in the heart) are involved, respectively. We hypothesized that there is a chiral recognition of doxazosin enantiomers in the 3 targets. Using isolated rat aorta (α(1D)-adrenoceptors) and rabbit prostate (α(1A)-adrenoceptors), we examined pA(2) and pK(B) values of doxazosin enantiomers. We observed chronotropic and inotropic effects of doxazosin enantiomers in isolated rat and rabbit heart tissues. (-)Doxazosin and (+)doxazosin produced a shift to the right of concentration-contraction curves for noradrenalin (aorta) and phenylephrine (prostate smooth muscle). The pA(2) value of (-)doxazosin (8.625 ± 0.053) was smaller than (+)doxazosin (9.503 ± 0.051) in rat aorta, but their pK(B) values in rabbit prostate were the same. In rat and rabbit heart tissues, (+)doxazosin (3-30 µmol·L(-1)) significantly decreased atrial rate, and produced negative inotropic effects; however, (-)doxazosin did not affect the atrial rate, and produced positive inotropic effects in the atria. Thus, the chiral carbon atom of doxazosin does not affect its activity at the therapeutic target of α(1A)-adrenoceptors in the prostate, but significantly changes its blocking activity against α(1D)-adrenoceptors in the aorta, and produces opposite inotropic effects in the atria via an α(1)-adrenoceptor-independent mechanism.

Objective: To investigate the prevalence of eight common rheumatic diseases in a large Chinese population., Methods: A population-based epidemiological investigation of the prevalence of eight common rheumatic diseases in a suburb of Beijing was conducted in 14 642 individuals. A community-based survey was carried out using a screening questionnaire. Positive responders were included in a clinical and laboratory examination. Diagnosis was based on the criteria of ACR or those used widely in literature., Results: A total of 10 556 inhabitants were interviewed. Forty-three cases of RA were identified with an age-adjusted prevalence of 0.28% (95% CI 0.19%, 0.41%). Gout was diagnosed with a crude prevalence of 0.09% (95% CI 0.05%, 0.17%). Psoriasis was reported in 28 individuals with a prevalence of 0.27% (95% CI 0.18%, 0.38%). This included two cases diagnosed with PsA, resulting in a prevalence of 7.14% (95% CI 0.88%, 23.5%) in psoriasis patients and 0.02% (95% CI 0%, 0.07%) in the general population. Three individuals were identified with SLE, with a prevalence of 0.03% (95% CI 0%, 0.06%). One individual was identified with SSc and the calculated prevalence was 0.01% (95% CI 0%, 0.05%). One case of Behçet's disease was identified, giving a prevalence of 0.01% (95% CI 0%, 0.05%)., Conclusion: This large-scale epidemiological survey provides an estimate of the burden of rheumatic diseases in China.

Aim: To investigate the effects of exhaustive swimming exercise on P2X1 receptor- and α1-adrenoceptor-mediated vasoconstriction of different types of arteries in rats., Methods: Male Wistar rats were divided into 2 groups: the sedentary control group (SCG) and the exhaustive swimming exercise group (ESEG). The rats in the ESEG were subjected to a swim to exhaustion once a day for 2 weeks. Internal carotid, caudal, pulmonary, mesenteric arteries and aorta were dissected out. Isometric vasoconstrictive responses of the arteries to α,β-methylene ATP (α,β-MeATP) or noradrenaline (NA) were recorded using a polygraph., Results: The exhaustive swimming exercise did not produce significant change in the EC(50) values of α,β-MeATP or NA in vasoconstrictive response of most of the arteries studied. The exhaustive swimming exercise inhibited the vasoconstrictive responses to P2X1 receptor activation in the internal carotid artery, whereas it reduced the maximal vasoconstrictive responses to α1-adrenoceptor stimulation in the caudal, pulmonary, mesenteric arteries and aorta. The rank order of the reduction of the maximal vasoconstriction was as follows: mesenteric, pulmonary, caudal, aorta., Conclusion: Exhaustive swimming exercise differentially affects the P2X1 receptor- and α1-adrenoceptor-regulated vasoconstriction in internal carotid artery and peripheral arteries. The ability to preserve purinergic vasoconstriction in the peripheral arteries would be useful to help in maintenance of the basal vascular tone during exhaustive swimming exercise.

Hydroxyapatite ceramics have been widely investigated for bone regeneration due to their high biocompatibility. However, few studies focus on their mechanical characteristics after implantation. In this study, the finite element (FE) method was used to evaluate the mechanical properties of a fully interconnected porous hydroxyapatite (IPHA) over time of implantation. Based on the micro-CT images obtained from the experiments dealing with IPHA implanted into rabbit femoral condyles, three-dimensional FE models of IPHA (1, 5, 12, 24, and 48 weeks after implantation) were developed. FE analysis indicated that the elastic modulus gradually increased from 1 week and reached the peak value at 24 weeks, and then it kept at high level until 48 weeks postoperatively. In addition, as a local biomechanical response, strain energy density became to distribute evenly over time after the implantation. Results confirmed that the mechanical properties of IPHA are strongly correlated to bone ingrowth. The efficiency of the proposed numerical approach was validated in combination with experimental studies, and the feasibility of applying this approach to study such implanted porous bioceramics was proved.

Moxonidine and clonidine, which are imidazoline compounds, are sympathetic modulators used as centrally acting antihypertensive drugs. Moxonidine, clonidine, and agmatine produce extensive effects in mammalian tissues via imidazoline recognition sites (or receptors) or α(2)-adrenoceptors. To investigate the effects of imidazolines on the function of the urinary bladder, we tested the effects of moxonidine, clonidine, and agmatine on the neurogenic contraction induced by electric field stimulation, and on the post-synaptic receptors in isolated urinary bladder detrusor strips from rabbit. Both moxonidine at 1.0-10.0 µmol/L and clonidine at 0.1-10.0 µmol/L inhibited electric-field-stimulation-induced contraction in a concentration-dependent manner, but not agmatine (10.0-1000.0 µmol/L). Both moxonidine and clonidine failed to affect carbachol or adenosine-triphosphate-induced contractions; however, 1000.0 µmol/L agmatine significantly increased these contractions. Our study indicates that (i) moxonidine and clonidine produce a concentration-dependent inhibition of the neurogenic contractile responses to electric field stimulation in isolated detrusor strips from male New Zealand rabbits; (ii) post-synaptic muscarinic receptor and purinergic receptor stimulation are not involved in the responses of moxinidine and clonidine in this study; (iii) the inhibitory effects of these agents are probably not mediated by presynaptic imidazoline receptors.

Objective: Anxiety and depression disorder are the most prevalent mental health problems. However, few studies are available pertaining to these problems among Chinese doctors, especially the assessment of the anxiety and depression symptoms among primary-care providers. The aim of this study was to assess the anxiety and depression symptoms among Chinese primary-care physicians and their associated factors., Methods: A cross-sectional study was conducted among 451 primary-care physicians in Shanghai China (effective response rate was 79.8%). There were 177 male physicians and 274 female physicians with average age of 37.8 (SD +/- 11.1) years. Questionnaire pertaining to depression disorder was indicated by the Zung Self-Rating Depression Scale (SDS) and anxiety disorder was indicated by the Zung Self-Rating Anxiety Scale (SAS)., Results: The average SAS and SDS standard scores of the primary-care physicians were 41.1 +/- 11.5 and 46.5 +/- 11.8 respectively. Both of the scale scores were higher than those of Chinese national norms (P both < 0.001). SDS standard score > or = 53 and SAS standard score > or = 50 were regarded as screening-positive criteria. SAS and SDS screening positive rates of primary-care physicians were 18.0% and 31.7% respectively. In addition, married/cohabited and divorced/widowed physicians aged over 30 years with educational background of junior college had higher risks of anxiety and depression disorders., Conclusions: Chinese primary-care physicians were at considerably high risk of anxiety and depression disorders, which was worthy of attention during healthcare system reform in China.

(-)Doxazosin, one of (±)doxazosin enantiomers, was speculated to have a pharmacological enantioselectivity between the cardiovascular system and the urinary system by comparison with (+)doxazosin. Therefore, to evaluate the potential benefits of (-)doxazosin in the treatment of benign prostate hyperplasia, we compared the effects of the 3 agents, using rat mesenteric artery preparations and obstructed bladder strips. Concentration-response curves for carbachol (contractile response) and isoprenaline (relaxant response) in detrusor muscle strips of the bladder outlet obstruction (BOO) rats were shifted to the left, with significant increases in the Emax values, and significant decreases in the EC50 values by comparison with the sham-operated rats (P < 0.05, n = 10). The enhanced responses in detrusor muscle strips of the BOO rats treated with (±)doxazosin and its enantiomers at 3 mg·(kg body mass)(-1)·day(-1) for 2 weeks returned to normal levels, and the 3 agents inhibited the enhanced responses to carbachol and isoprenaline to the same extent. On the other hand, the 3 agents uncompetitively inhibited the vasoconstrictive response curves for NA in the rat isolated mesenteric artery, and the pKB value of (-)doxazosin at vascular α1-adrenoceptors was significantly smaller (P < 0.05, n = 6) than that of (+)doxazosin or (±)doxazosin. In conclusion, although (-)doxazosin inhibits vascular functional α1-adrenoceptors more weakly than (+)doxazosin, both agents equally ameliorate the enhanced responses in detrusor muscle of BOO rats, suggesting that the chiral carbon atom in the molecular structure of doxazosin does not affect its beneficial effects in the bladder smooth muscle of BOO rats.

P2X(1) receptors, the major subtype of P2X receptors in the vascular smooth muscle, are essential for α,β-methylene adenosine 5'-triphosphate (α,β-MeATP)-induced vasoconstriction. However, relative physiological significance of P2X(1) receptor-regulated vasoconstriction in the different types of arteries in the rat is not clear as compared with α(1)-adrenoceptor-regulated vasoconstriction. In the present study, we found that vasoconstrictive responses to noncumulative administration of α,β-MeATP in the rat isolated mesenteric arteries were significantly smaller than those to single concentration administration of α,β-MeATP. Therefore, we firstly reported the characteristic of α,β-MeATP-regulated vasoconstrictions in rat tail, internal carotid, pulmonary, mesenteric arteries, and aorta using single concentration administration of α,β-MeATP. The rank order of maximal vasoconstrictions for α,β-MeATP (E (max·α,β-MeATP)) was the same as that of maximal vasoconstrictions for noradrenaline (E (max·NA)) in the internal carotid, pulmonary, mesenteric arteries, and aorta. Moreover, the value of (E (max·α,β-MeATP)/E (max·KCl))/(E (max·NA)/E (max·KCl)) was 0.4 in each of the four arteries, but it was 0.8 in the tail artery. In conclusion, P2X(1) receptor-mediated vasoconstrictions are equally important in rat internal carotid, pulmonary, mesenteric arteries, and aorta, but much greater in the tail artery, suggesting its special role in physiological function.

In the present study, we observed the effects of an α(1)-adrenoceptor agonist (phenylephrine), β-adrenoceptor agonist (isoprenaline), muscarinic cholinoceptor agonist (carbachol), and α(1)-adrenoceptor antagonist (doxazosin) on the bladder micturition function in anesthetized mice. Changes in bladder pressure in response to filling and blood pressure were recorded by using a data acquisition system. Phenylephrine (50 to 800 μg/kg) increased vesical micturition pressure in a dose-dependent manner but increased micturition basal pressure only at 800 μg/kg. Carbachol (3 to 7 μg/kg) increased the intercontraction interval and micturition time in a dose-dependent manner but increased micturition basal pressure only at 7 μg/kg. Isoprenaline (10 to 1000 μg/kg) increased micturition time and decreased vesical micturition pressure in a dose-dependent manner. Doxazosin (10 to 1000 μg/kg) did not affect bladder micturition function but dose-dependently inhibited phenylephrine-induced increases in vesical micturition pressure. Carbachol (7 μg/kg) and isoprenaline (1 mg/kg) caused a transient fall in blood pressure, whereas doxazosin (1 mg/kg) had a long-lasting hypotensive effect. The maximal decrease in systolic and mean blood pressure by carbachol did not differ from that by doxazosin and isoprenaline, respectively. Phenylephrine (800 μg/kg) transiently increased the blood pressure of anesthetized mice. These results indicate that activation of muscarinic cholinoceptors decreases voiding frequency and increases bladder capacity in anesthetized mice. Activation of α(1)-adrenoceptors mainly increases vesical micturition pressure, whereas activation of β-adrenoceptors decreases vesical micturition pressure and prolongs micturition time in anesthetized mice.

Objective: To investigate the clinical significance of D-dimer in systemic lupus erythematosus (SLE)., Methods: The study group comprised 261 SLE patients who were admitted in ward from 2005 to 2008 in Peking University People's Hospital. Collect the clinical data to investigate the clinical significance of D-dimer., Results: (1) The D-dimer levels of 56 patients were increased due to coexist reduced renal function, infections, disseminated intravascular coagulation (DIC), liver disorders, pregnancy and injury. With the exception of above patients, 142 (69.3%) patients were increased in total 205 patients. (2) The level of D-dimer was positively correlated with SLE disease activity index (SLEDAI) score (r = 0.598, P = 0.000), and was associated with anti-dsDNA antibody, ESR, C-reactive protein (CRP) and complement C(3) and C(4). (3) D-dimer level was associated with important organ involvement. (4) All patients with thrombosis had increased D-dimer, but patients without thrombosis had normal or increased D-dimer levels., Conclusion: The level of D-dimer elevates in patients with active disease or important organ involvement, it can not identify thrombosis. All patients with thrombosis had increased D-dimer levels.

Objectives: The aim of the present work is to investigate the effects of cementum-dentine junction (CDJ) and cementum on the stress distribution in the periodontal ligament (PDL) and alveolar bone., Methods: Based on the anatomical profiles and the recently reported theories about the tooth attachment mechanism, the finite element (FE) model of a mandibular second premolar along with its detailed supporting structures was developed. The effect of CDJ and cementum was evaluated by comparing the resulting stresses of FE models of the second mandibular premolar with and without CDJ and cementum in tooth supporting structure., Results: The stress levels are higher in the structure without CDJ and cementum than that with CDJ and cementum. The function of CDJ and cementum is as a cushion pad decreasing the stress in the PDL and alveolar bone under loading., Conclusions: As a major result of this study, it can be concluded that the CDJ and cementum significantly influence the stress distribution within the tooth supporting structure. However, most of the reported FE analysis did not take CDJ and cementum into account, which possibly resulted in overestimated stress values in the PDL and alveolar bone. From a bio-engineering perspective, the results of this study provide guidance for the design of dental implants and the application of orthodontic force system as well., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Aimed at controlling the nitrogen loss during composting, the mixture of magnesium hydroxide (Mg(OH)( 2)) and phosphoric acid (H(3)PO(4)) (molar ratio 1:2) were utilized as additives to avoid increasing total salinity. In trial TA, the additives were put into absorption bottles connecting with a gas outlet of fermentor (ex situ method); in trial TB, the additives were directly added to the composting materials (in situ method). During the 26 day composting period, the temperature, pH, total organic carbon (TOC), total nitrogen (TN), ammonium nitrogen (NH(4)(+)-N), total phosphorus (TP), available phosphorus (AP) and germination index (GI) were measured. The experimental results show that the additives reduced the pH, while NH( 4)(+)-N and TN were obviously improved. NH(4)( +)-N was 11.9 g kg(-1) and 3 g kg(- 1) in amended compost trial (TB) and unamended compost trial (TA), respectively; TN increased from 26.5 g kg(-1) to 40.3 g kg(-1) in TB and increased from 26.5 g kg( -1) to 26.8 g kg(-1) in TA. Analysis of the TOC and carbon mass revealed that absorbents accelerated the degradation of organic matter. The germination index test showed the maturity of TB (102%) was better than TA (82%) in final compost. Furthermore, TP and AP were also obviously improved. X-ray diffraction analysis of precipitation showed that the precipitation in absorption bottle of TA was newberyite (MgHPO( 4) 3H(2)O), however, the crystal in the TB compost was struvite (MgNH(4)PO(4) 6H(2)O: magnesium ammonium phosphate). These results indicated that Mg(OH)(2) and H(3)PO( 4) could reduce the ammonia emission by struvite crystallization reaction. Optimal conditions for struvite precipitation should be determined for different systems.

Objective: To observe the effects of (-)doxazosin(DOX), (+)DOX and (+/-)DOX on serum lipid levels and the mortality rates of the rabbits fed by an atherogenic diet., Methods: Male white New Zealand rabbits were fed by an atherogenic diet for 4 weeks. 8 rabbits whose serum TC <10 mmol/L were confirmed as normal diet group and were fed normally. 40 rabbits whose serum TC >10 mmol/L were randomly divided into 4 groups (n=10): atherogenic diet group, atherogenic diet with (-)DOX group, atherogenic diet with (+)DOX group and atherogenic diet with (+/-)DOX group, which were intraperitoneally injected with (-)DOX, (+)DOX and (+/-)DOX for 9 weeks respectively. Normal and atherogenic diet group were intraperitoneally injected with double distilled water. After 9 weeks administration of (+/-)doxazosin and its enantiomers, effects of the three agents on serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were observed., Results: The mortality rate of the rabbits fed by an atherogenic diet for 13 weeks was 40%, and it was much higher than that of the rabbits fed by a normal diet (10%). The mortality rates in the rabbits treated with (-)DOX and (+/-)DOX were lower than that in the rabbits fed by a normal diet (10%). Serum LDL-C level of the rabbits was increased markedly after 4 weeks of atherogenic diet, and it was further increased significantly (P < 0.05 and P < 0.01) during the continued 9 weeks of atherogenic diet. However, serum LDL-C levels were not further increased significantly (P > 0.05) during the continued 9 weeks of atherogenic diet in the rabbits treated with (-)DOX, (+)DOX and (+/-)DOX, respectively., Conclusion: (-)DOX and (+/-)DOX increase the survival rate and improve LDL-C disorder mildly in the rabbits fed by an atherogenic diet. The improvements in LDL-C induced by (-)DOX and (+/-)DOX, however, might not be the reason for exploration about the increased survival rate in the rabbits fed by an atherogenic diet.

Nine potentially harmful heavy metals (Cd, Co, Cr, Cu, Hg, Mn, Pb, Ni, and Zn) were measured in 477 topsoil samples collected from urban-rural areas in the city of Wuhan in order to identify their concentrations and possible sources, and characterize their spatial variability for risk assessment. Results showed that in most rural areas heavy-metal concentrations in soil were similar to their natural background values, but Cd, Cu, Hg, Pb, and Zn concentrations were relatively higher in densely populated districts and around industrial facilities. Multivariate analyses (correlation matrix, principal component analysis, and cluster analysis) indicated that Cd, Cu, Hg, Pb, and Zn were mainly derived from anthropogenic inputs, and Co, Cr, and Mn were controlled by natural source, whereas Ni appeared to be affected by both anthropogenic and natural sources. The result of risk assessment indicated that nearly 48% of the study area suffered from moderate to severe contamination.

The surface of commercially pure titanium was modified by anodization treatment in a phosphoric acid solution at different voltages: 100 V, 200 V and 300 V. The surface characteristics of anodic TiO2 layers and their influence on the cell response were investigated. Micrographs by scanning electron microscopy revealed that the dense and uniform oxide layer obtained at 100 V exhibits a nanostructured surface which is similar to the surface of natural tooth cementum. In contrast, porous oxide layers without nanometer features were produced at higher voltages. Thin film x-ray diffraction analysis confirmed the existence of anatase in the oxide layer obtained at 300 V, but not in oxide layers obtained at 100 V and 200 V. The in vitro biocompatibility study of oxide layers demonstrated greater cell adhesion and proliferation of the oxide layer obtained at 100 V compared to the other two kinds of oxide layers.

Background: (-)Doxazosin is one of the enantiomers of (+/-)doxazosin, and it was reported that (-)doxazosin possessed higher selectivity for lower urinary tract between the cardiovascular system and the urinary system in the animal experiments in comparison with that of (+/-)doxazosin and (+)doxazosin. Therefore, it is important to know whether (-)doxazosin has a therapeutic effect on the hyperplastic prostate., Methods: (-)Doxazosin and (+/-)doxazosin were administered intragastrically to prostatic hyperplasia rats, induced by testosterone propionate for 4 weeks, and each experimental group contained 8 animals. The histomorphologic changes of the prostate were observed under light microscope, the quantitative analysis of the prostatic glandular cavity was performed using an image analysis system, and the cell apoptosis was detected by using flow cytometry., Results: In comparison with model-control group, the volume index of the prostate in (-)doxazosin 3.0 mg/kg group became significantly smaller. The maximal diameter, perimeter, and area of the hyperplastic prostate glandular cavity, and the glandular epithelial cell height in (-)doxazosin (0.3, 1.0, and 3.0 mg/kg) groups and (+/-)doxazosin group were significantly reduced. (-)Doxazosin and (+/-)doxazosin did not significantly affect cell cycle distribution and cell proliferation index of the hyperplastic prostate. However, apoptotic rates of the prostatic cells in (-)doxazosin (0.3, 1.0, and 3.0 mg/kg) groups and (+/-)doxazosin group were significantly increased in comparison with those of model-control group., Conclusions: Both (-)doxazosin and (+/-)doxazosin inhibit the prostatic hyperplasia induced by testosterone propionate in castrated rats. The induction of prostate cell apoptosis might be one of the mechanisms underlying the therapeutic role of (-)doxazosin.

Objective: To identify interleukin-17 (IL-17 )-producing CD8 positive T cells from patients with rheumatoid arthritis (RA), and investigate its cytokines as well as their correlations., Methods: Peripheral blood got from 39 RA patients and 40 healthy donors. Flow cytometry was used to analyze the subsets of T cells in peripheral blood from these 39 RA patients and 27 healthy donors. 11-17, IL-6, and IL-23 levels in sera of all these people were tested by ELISA., Results: The median of CD8 IL-17+ T cells from RA patients was 2.7% (95% confidence internal was 1.55%-3.74%); the median of these cells from healthy controls was 1.61% (95% confidence internal was 1.25%-2.61%). CD8+ IL-17+ T cells elevated significantly in RA(P < 0.05). As the production of CD8+ IL-17+ T cells, the IL-17 levels in sera of RA patients and healthy controls were (429 +/- 502) ng/L and (13 +/- 30) ng/L respectively. The IL-17 level in RA is higher than that in healthy people (P < 0.01). Meanwhile, to constitute CD8+ IL-17+ T cell polarizing condition, IL-23 and IL-6 in sera of RA were (157.83 +/- 27.07) ng/L and (32.67 +/- 34.50) x ng/L individually. These two cytokines in healthy controls were (21.97 +/- 3.52) ng/L and (1.82 +/- 1.51) ng/L severally. IL-6 and IL-23 increased clearly in peripheral blood of RA patients as compared with healthy donors (P < 0.01)., Conclusions: This study suggested that elevated CD8+ IL-17+ T cells which involved in IL-17 secretion may depend on increased IL-6 and IL-23 in peripheral blood of rheumatoid arthritis.

Aimed at controlling the nitrogen loss caused by the ammonia gas emission during composting, the mixtures of magnesium hydroxide [Mg(OH)2] and phosphoric acid (H3PO4) were added into composting materials of swine manure and cornstalk. After 26 d composting, ammonical nitrogen and total nitrogen were improved obviously,which were 10.7 g x kg(-1) and 36.9 g x kg(-1) respectively in amended treatment (B), while they were 7.7 g x kg(-1) and 26.8 g x kg(-1) in un-amended trial. By analysis of the total organic carbon, t suggested that amendments accelerated the degradation of organic matter, germination index test showed the maturity of trial B(96%) was better than trial A(82%) in final compost. The scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis confirmed the existence of struvite (MgNH4PO4 x 6H2O). These results indicated that Mg (OH)2 and H3PO4 could accelerate the degradation of organic matter, and reduce the ammonia emission by struvite crystallization reaction.

This study is to observe the difference in pharmacological characteristics between circular smooth muscles of rat isolated gastric body and gastric fundus, and to investigate the effects of nucleoside and nucleotide on circular smooth muscle of the rat gastric body and the involved receptors. Circular muscle strips of the rat gastric body and gastric fundus were prepared, and contractile responses to agonists were investigated with a technique of drug-receptor interaction in functional system. There was no significant difference between the circular muscle strips of the gastric body and gastric fundus in the responses to KCl, and no difference in EC50 values of contractile responses for 5-HT and His between the two kinds of preparations (P > 0.05). However, Emax values of contractile responses to 5-HT and His [(0.81 +/- 0.26) and (0.88 +/- 0.27) g] in gastric body were significantly smaller than those in gastric fundus [(2.67 +/- 0.61) and (1.90 +/- 0.68) g, P < 0.01], and EC50 value of CCh produced contractile response [(0.45 +/- 0.15) micromol x L(-1)] in gastric body was significantly higher than that in gastric fundus [(0.20 +/- 0.09) micromol x L(-1), P < 0.01]. In precontracted circular muscle strips of the gastric body, ATP (0.1-3000 micromol x L(-1)) produced only a contractile response concentration-dependently, but the same concentration of ATP induced a biphasic response (relaxation followed by a contraction) in precontracted circular muscle strips of the gastric fundus. ATP, UTP, ADP, 2-MeSATP and alpha,beta-MeATP produced contractile responses concentration-dependently in circular muscle strips of the rat gastric body. The EC50 value for 2-MeSATP [(7.2 +/- 5.2) nmol x L(-1)] was about 500 times lower than that for Ach [(3.47 +/- 1.20) micromol x L(-1)]. The rank order of potency for the contraction was 2-MeSATP>>ADP>ATP=UTP>alpha,beta-MeATP>>adenosine. The contractile responses to ATP and UTP were not significantly affected by phentolamine, propranolol, atropine or tetrodotoxin. In conclusion, there is a significant difference in pharmacological characteristics between the circular smooth muscles of the rat gastric body and gastric fundus and nucleotides might be important mediators responsible for the contraction via a specific P2Y receptor in circular smooth muscle of the rat gastric body.

We investigated the pharmacological profile of the vasoconstrictive response to clonidine in the isolated rabbit ear vein, and compared the characteristics of clonidine with those of noradrenaline and moxonidine. The maximal vasoconstrictive responses to clonidine and moxonidine in the rabbit ear vein were 35.94+/-11.18% and 88.78+/-11.54% of the maximum response to noradrenaline, respectively. Prazosin 0.1 microM inhibited the vasoconstriction induced by lower concentrations of noradrenaline, and the concentration-dependent response curve for noradrenaline was significantly shifted to the right by 1 microM prazosin. Yohimbine (0.1 and 0.5 microM) only decreased the vasoconstrictive response to lower concentrations of noradrenaline, but did not affect the response to higher concentrations. Vasoconstrictive responses to lower but not higher concentrations of clonidine and moxonidine were inhibited by 0.1 microM yohimbine. In contrast, the same concentration of yohimbine significantly potentiated the maximal response to a high concentration of clonidine by 24.06%. In isolated rabbit ear vein pretreated with 0.1 microM yohimbine, prazosin competitively inhibited the concentration-response curve for clonidine with a pA(2) value of 8.05+/-0.06. We conclude that clonidine acts mainly on alpha(2)-adrenoceptors to produce vasoconstriction in the rabbit ear vein; however, in the preparation pretreated with yohimbine, the clonidine-induced vasoconstriction is mediated via alpha(1)-adrenoceptors and its maximal vasoconstriction is significantly potentiated.

A technique based on Fourier transform infrared (FTIR) spectrometry was used to detect the physiological changes in chemical composition of Phytolacca americana under a wide range of Mn2+ treatments (0, 0.125, 0.25, 0.5 and 1 g x kg(-1)). Using the roots, stems and leaves of phytolacca americana, absorption bands corresponding to carbohydrates, ester and proteins varied differently. The absorption band heights at 3 000 and 2 916 cm(-1) of stem tissues rose firstly and then decreased, indicating the exudation and transporting situation of organic substances which served as organic osmotic contents to enhance manganese tolerance under low treatments; Meanwhile, the band heights at 2 922 cm(-1) (roots) and 1 606 cm(-1) (leaves) which have different tendency in accordance with Mn treatments showed that the capability to chelate Mn decreased under higher manganese concentration. In addition, the changes of the bands at 1 732 and 1 026 cm(-1) (roots), 1 028 cm(-1) (stems), 1 052 and 967 cm(-1) (leaves) differed from each other, suggesting that under the conditions of severe Mn stress the ex-oxidation of membrane lipid increased; Otherwise, the band heights at 1 375 cm(-1) increased firstly and then decreased, representing that the cell wall improved Mn resistance by increasing cation-exchange capacity (CEC). The result also implied that it is practical to apply FTIR to the research comparing the chemical differences of phytoaccumulators under metal treatments.

The aim of this study is to investigate the effect of isosorbide-5-mononitrate (ISMN) on the electric field stimulation induced sympathetic purinergic vasoconstriction of the rabbit saphenous arterial rings. Isometric vasoconstrictive responses to electric field stimulation and to exogenous noradrenaline and adenosine triphosphate were recorded. We found that the vasoconstrictive responses to electric field stimulation (15 V, 1 ms pulse duration, 2 - 16 Hz) were frequency-dependant in the rabbit saphenous arterial rings, and abolished by tetrodotoxin (0.1 micromol x L(-1)). The alpha1-adrenoceptor antagonist prazosin (1 micromol x L(-1)) did not affect the vascular responses to the electric field stimulation (2 -8 Hz). After a combination treatment with both alpha,beta-meATP (3 micromol x L(-1), desensitizing P2X1 receptors) and prazosin (1 micromol x L(-1)), the vasoconstrictive responses to electric field stimulation were abolished. When the arterial preparation was treated with ISMN (one preparation was exposed to only one concentration of ISMN), ISMN at 0.1 mmol x L(-1) significantly inhibited the vasoconstriction induced by electric stimulation at 8 Hz, 0.3 and 1.0 mmol x L(-1) significantly inhibited the vasoconstrictive responses to electric stimulation at 2 - 16 Hz. The highest concentration of ISMN (1.0 mmol x L(-1)) reduced the vasoconstrictive responses by 46% (2 Hz), 47% (4 Hz), 34% (8 Hz) and 22% (16 Hz), separately. ISMN (0.3 and 1.0 mmol x L(-1)) did not affect the vascular responses to exogenous noradrenaline (0.01-100 micromol x L(-1)) and adenosine triphosphate (1 mmol x L(-1)). It is reasonable to suggest that ISMN inhibits the purinergic vasoconstriction induced by sympathetic nerve stimulation via a prejunctional mechanism.