Objective To investigate the function of triggering receptor expresses on myeloid cells receptor-1 (TREM-1) in lymphocyte differentiation and regulation of Aspergillus infected immunosuppressed rats.Methods Cyclophosphamide (CTX) was intraperitoneally injected and Fumigatus spore suspension was inhaled by percutaneous tracheostomy to establish the immunosuppressive invasive pulmonary aspergillosis (IPA) rat model.After 24 h, 48 h, 72 h and 96 h inoculation, rats were sacrificed.Lung tissue specimens, bronchoalveolar lavage fluid (BALF) , and plasma samples were collected.Plasma and BALF sTREM-1, plasma T cell-specific transcription factor (T-box expressed in T cells, T-bet) and eomesodermin(Eomes) were detected by ELISA.Biopsy specimens of lung tissue were used for periodic acid-schiff (PAS) staining and culture.Results The mortality rate of immunosuppressed rats after Aspergillus inhalation for 96 h was as high as 54.4％.Biopsy of lung tissue suggested acute inflammatory cell infiltration, interstitial lung congestion, alveolar structural damage, and visible Aspergillus hyphae in alveoli.Compared with normal control group[(110.50 ± 7.70)ng/L], plasma sTREM-1 in study groups were significantly increased [IPA : (146.77 ± 10.41) ng/L;CXT + IPA at 24 h : (226.00 ± 11.88) ng/L;CTX + IPA at 48 h : (200.77 ± 10.63) ng/L;P ＜ 0.05], so were T-bet levels [IPA : (561.17 ± 7.23) μg/L;CXT + IPA at 24 h : (647.00 ± 33.03) μg/L;CTX + IPA at 48 h : (619.23 ± 87.44) μg/L;control group : (340.03 ± 26.32) μg/L;respectively, P ＜0.05].However, plasma Eomes levels in IPA group, CTX + IPA at 24 h and 48 h were significantly lower compared with that in normal controls [IPA : (7.96 ± 0.65) ng/L;CXT + IPA at 24 h : (3.97 ± 0.35) ng/L;CTX + IPA at 48 h : (4.00 ± 0.74) ng/L;control group : (8.38 ± 0.51) ng/L;respectively,P ＜0.001].Compared with those in CTX + IPA vaccination after 24 h and 48 h, plasma sTREM-1 [(106.67 ±7.64)ng/L;(133.27 ± 32.79) ng/L] and T-bet [(299.64±63.07)μg/L;(398.02 ± 109.22) μg/L] in CTX + IPA at 72 h and 96 h inoculation were significantly lower (P ＜ 0.001).While Eomes [(8.38 ± 0.54) ng/L;(8.40 ± 0.70) ng/L] raised significantly higher (P ＜ 0.001).Compared with the control group, sTREM-1 levels in BALF of IPA + CTX 24 h, 48 h, 72 h, and 96 h groups were consistently high (P ＜ 0.05).Pearson correlation analysis showed that sTREM-1 and T-bet had a significant positive correlation (r =0.91, P ＜ 0.001), yet Eomes was negatively correlated with them (r =-0.788, P ＜ 0.001).Conclusions sTREM-1 in rat plasma and BALF appears highly expressed in immune compromised Aspergillus infected rat model.Plasma sTREM-1 is closely correlated with T-bet and Eomes levels, which suggests that TREM-1 may be involved in lymphocytic regulation and differentiation during fungal infection.

Objective To investigate the prevalence and attitude of smoking and its influencing factors among residents in Hongkou District of Shanghai,so as to provide evidence for tobacco control. Methods Nine hundred and sixty residents in Hongkou District of Shanghai aged 15 to 69 years were selected by multi-level random sampling,among whom 958 completed the investigations on smoking status. Results The smoking rate and standardized smoking rate were 20.04% and 18.73%,respectively.The smoking rate and standardized smoking rate of males were 41.05% and 30.07%,and those of females were 0.80% and 1.70%,respectively.The smoking rate of males was higher than that of females(RR=0.02,95%CI: 0.01-0.03).The smoking rates of age groups of 25 years old and over were higher than those of 15 to 24 years old,and the smoking rate of subjects with or above junior college education was lower than that of subjects with or below middle school education(RR=0.45,95%CI: 0.25-0.79).Subjects who drank alcohol smoked more than those did not(RR=2.68,95%CI: 1.76-4.09).Lower annual per capita income and higher knowledge on smoking hazard led to more tendance to object to smoking and agree with anti-smoking. Conclusion The prevalence of smoking of residents aged 15 to 69 years in Hongkou District of Shanghai was relatively lower.Age,gender,education status and alcohol drinking were influencing factors of smoking.Education on tobacco control among subjects aged more than 35 years should be strengthened,and more attention should be paid to those with lower education.Besides,education on alcohol control should be managed together with tobacco control.

This study was aimed to investigate the effects of high-dose strictosamide injection on cardiovascular sys-tem of anesthetized beagle dogs and to examine the inhibition of strictosamide on ion channels in vitro. Indexes such as changes of systolic blood pressure (Sys), diastolic blood pressure (Dia), mean blood pressure (MBP), heart rate (HR), PR, QRS, QT, QTcb and QTcv at different time points before and after strictosamide injection in dogs were monitored by the polygraph system. The inhibition of strictosamide at different concentrations on hERG potassium channel in CHO-hERG cells and Nav1.5 sodium channel in HEK-293-Nav1.5 cells were measured by whole-cell patch-clamp method. The results showed that compared with the blank control group, Sys, Dia, MBP and HR were obviously declined 15 min after medication in the strictosamide (60, 18 mg·kg-1) group and the vehicle-control group (containing tween-80) (P < 0.05). After medication, all indexes were recovered. Compared to the vehicle-control group, there were no significant differences at different time points in each medication groups. Compared with the blank control group and before medication, the QT interval, QTcb and QTcv were significantly prolonged 15 min af-ter medication in the strictosamide (60, 18, 6 mg·kg-1) group and the vehicle-control group (P< 0.05). When medi-cation stopped, indexes were recovered at certain level. Compared with the vehicle-control group, there were no sig-nificant differences of QT interval, QTcb and QTcv of each medication group at different time points (P> 0.05). The inhibition of strictosamide on hERG potassium channel and Nav1.5 sodium channel were weak with IC50 values of 560.8 μM and > 900 μM, respectively, which were far greater than the positive controls. It was concluded that sin-gle, high-dose intravenous injection of strictosamide may lead to a lower blood pressure, a slower heart rate and a prolongation on the QT interval in beagle dogs, which returned to basal levels when medication stopped. It was spec-ulated that the reduction of blood pressure and the slowing of heart rate were related to tween-80 contained in the vehicle control group. No significant inhibitory effects were detected on hERG potassium channel and Nav1.5 sodium channel in vitro, which suggested that other mechanisms may be involved in strictosamide-induced QT interval pro-longation in animals.

OBJECTIVETo observe the clinical efficacy difference between segmentation scraping and conventional acupuncture for cervical spondylosis (CS) so as to provide effective treatment method.

METHODSEighty-five cases of cervical type of CS were randomly divided into a scraping group (44 cases) and an acupuncture group (41 cases). The segmentation scraping therapy was used in the scraping group. The scraping group was treated with focusing on scraping the head and joint part of neck and occiput in the upper cervical spine injury, and focusing on scraping the lower section of cervical and shoulder in the lower cervical spine injury, once every seven days, totally for 3 times. In the acupuncture group, Fengchi (GB 20),Wangu (TE 5), Tianzhu (BL 10),Neck-Jiaji (EX-B 2), etc. were selected,once daily,for 15 days. The visual analogue scale (VAS) was used to evaluate the immediate analgesic effect after the first treatment and the clinical efficacy was observed after the end of treatment.

RESULTSAfter the first treatment, the score of VAS was decreased significantly in the scaping group (P < 0.01), but there was no significant difference in the acupuncture group compared with those before treatment (P > 0.05); the score of VAS in the scaping group after the first treatment was lower than that in the acupuncture group (3.66 +/- 0.74 vs 5.43 +/- 0.35, P < 0.01). Compared with before treatment, the scores of VAS were decreased significantly after treatment in two groups (both P < 0.01), but without significant difference between two groups (P > 0.05); the effective rate was 95.5% (42/44) in the scaping group and 87.8% (36/41) in the acupuncture group, the curative effects were similar (P > 0.05).

CONCLUSIONBoth of scraping and acupuncture therapies have good analgesic effect for cervical spondylosis, and overall effects are similar, but the immediate analgesic effect of scraping thrapy is better than that of conventional acupuncture.

Acupuncture Points ; Acupuncture Therapy ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Neck Pain ; therapy ; Spondylosis ; therapy ; Treatment Outcome

Objective Type 1 diabetes mice model was established to investigate the changes of key enzymes involved in testosterone synthesis in testes of early diabetic mice.Methods Tatolly 20 male C57 mice were randomly divided into two groups:control and diabetic groups,and the diabetes mice were ip administered with a single dose of 150 mg/kg Streptozotocin.Four weeks after confirmation of diabetic model,the serum and testis were collected for further study.The qRT-PCR method was used to measure the expression of LHR and steroidogenesis synthetase StAR,P450scc,3β-HSD6,P450c17a1,and 17β-HSD3 mRNA.ELISA assay was performed to measure the levels of testosterone and luteinizing hormone (LH) in serum,and the enzymatic activities of 3β-HSD1,1P450c17 and 17β-HSD3 in testis tissue.Results Compared to control group,the levels of testosterone and LH of diabetic group declined significantly (P ＜ 0.05) after four weeks.The mRNA levels of LHR,StAR,CYP11a1,Hsd3b6,CYP17a1 and Hsd17b3,and enzymatic activities of 3β-HSD6,P450c17 and 17β-HSD3 were also decreased significantly compared with control group (P ＜ 0.05,0.01 and 0.001).Conclusion Expression of key enzymes of testosterone synthesis in testis of early diabetic mice decreases significantly.

BACKGROUND: Henoch-Schonlein purpura (HSP) is an immune complex-mediated disease predominantly characterized by the deposition of circulating immune complexes containing immunoglobulin A (IgA) on the walls of small vessels. Although the pathogenesis of HSP is not yet fully understood, some researchers proposed that B-cell activation might play a critical role in the development of this disease. OBJECTIVE: To investigate the serum levels of visfatin (pre-B-cell colony-enhancing factor), B-cell-activating factor (BAFF), and CXCL13, and to analyze their association with disease severity. METHODS: The serum levels of visfatin, BAFF, and CXCL13 were measured by using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 43 patients with HSP and 45 controls. The serum levels of IgA anticardiolipin antibodies (ACA) were detected by using a double-antigen sandwich ELISA. RESULTS: Levels of visfatin but not BAFF and CXCL13 were significantly elevated in the sera of patients with HSP in the acute stage, and restored to normal levels in the convalescent stage. Furthermore, serum levels of visfatin were significantly higher in patients with HSP having renal involvement than in those without renal involvement. Serum levels of visfatin were correlated with the severity of HSP and serum concentration of ACA-IgA. CONCLUSION: We show for the first time that the serum levels of visfatin are abnormally elevated in patients with HSP. Visfatin may be associated with the pathogenesis of HSP.
Antibodies, Anticardiolipin ; Antigen-Antibody Complex ; B-Cell Activating Factor ; B-Lymphocytes ; Chemokine CXCL13 ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin A ; Nicotinamide Phosphoribosyltransferase* ; Purpura, Schoenlein-Henoch*

The paper is to report the pharmacokinetic character of a series of chemical compounds in vitro and in vivo. Metabolism stability of a series of chemical compounds was screened by using rat liver microsomes. The samples of different chemical compounds were combined and then simultaneously detected by LC-MS/MS. Compounds y13, y12 and y11 were screened out by microstability assay in vitro. The pharmacokinetics of compounds y11, y12 and y13 was evaluated by using SD rat. The plasma samples were pooled at the same time. The plasma concentrations were determined by LC-MS/MS. The pharmacokinetic character of two compounds y13, y11 was good by screening in vivo, so they were developed for further research. High-throughput screening of drug candidates in vitro and in vivo was effective, to provide information for the chemical structure information and lower the drug development risk.
Animals ; Chromatography, Liquid ; methods ; Drug Evaluation, Preclinical ; methods ; Female ; High-Throughput Screening Assays ; methods ; Male ; Microsomes, Liver ; metabolism ; Pharmaceutical Preparations ; administration & dosage ; blood ; metabolism ; Pharmacokinetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; methods

As an important inorganic element, iodine not only plays an important role in human growth and metabolism, but also has an irreplaceable role in the chemical engineering, medicine, food and other fields.Thus the detection of iodine ion is of important significance.In this work, colorimetric recognition and sensing of iodine ion with high sensitivity was proposed based on target induced shielding of the peroxidase-like activity of bare platinum nanoparticles ( PtNPs ).This assay exhibited simplicity and cost-effectiveness.The recognition of iodine ion by bare PtNPs could be fulfilled in a few seconds and the assay could be accomplished within 10 min.The detection range for iodine ion was 20 nmol/L-5.0 μmol/L and the detection limit was 8 nmol/L ( S/N = 3 ).Furthermore, the new assay system did not require surface modification of nanoparticles, nor complex organic synthesis.This assay was successfully applied to detection of iodine concentration in real salt and water samples, exhibiting promising application prospects.

Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg^-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between C_max and AUC_0-5d in the two groups. The liquid preparation was the reference preparation, with C_max ratio of 101.6% and AUC_0-5d ratio of 101.9%, the 90% confidence interval of C_max was 79.42%-129.92%, and the 90% confidence interval of AUC_0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

OBJECTIVETo investigate the effects of endothelial microvesicles (EMVs) induced by calcium ionophore A23187 on H9c2 cardiomyocytes.

METHODSHuman umbilical vein endothelial cells (HUVECs) were treated with 10 micromol/L A23187 for 30 min. EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium. EMVs were characterized using 1 and 2 microm latex beads and anti-PE-CD144 antibody by flow cytometry. For functional research, EMVs at different concentrations were cocultured with H9c2 cardiomyocytes for 6 h. Cell viability of H9c2 cells and the activity of LDH leaked from H9c2 cells were tested by colorimetry. Moreover, apoptosis of H9c2 cells was observed through Hoechst 33258 staining and tested by FITC-Annexin V/PI double staining.

RESULTSEMVs were induced by A23187 on HUVECs, and isolated by ultracentrifugation. We identified the membrane vesicles (< 1 microm) induced by A23187 were CD144 positive. In addition, the EMVs could significantly reduce the viability of H9c2 cells, and increase LDH leakage from H9c2 cells in a dose dependent manner (P < 0.05). Condensed nuclei could be observed with the increasing concentrations of EMVs through Hoechst 33258 staining. Furthermore, increased apoptosis rates of H9c2 cells could be assessed through FITC-Annexin V/PI double staining by flow cytometry.

CONCLUSIONMicrovesicles could be released from HUVECs after induced by A23187 through calcium influx, and these EMVs exerted a pro-apoptotic effect on H9c2 cells by induction of apoptosis.

Annexin A5 ; Apoptosis ; Calcimycin ; pharmacology ; Calcium ; metabolism ; Cell Line ; Cell Membrane ; drug effects ; Coculture Techniques ; Flow Cytometry ; Fluorescein-5-isothiocyanate ; analogs & derivatives ; Human Umbilical Vein Endothelial Cells ; Humans ; Myocytes, Cardiac ; drug effects ; Staining and Labeling