Study on drug-target binding kinetics profiles of flavonoids in Chrysanthemum morifolium and xanthine oxidase / 中国中药杂志

Based on the target occupancy mathematical model, the binding kinetic process of potential active ingredients of lowering uric acid in Chrysanthemum morifolium with xanthine oxidase(XOD) was evaluated. The potential active ingredients of lowering uric acid in Ch. morifolium were screened by UPLC-Q-Exactivems MS technology, reference substance identification and in vitro enzymatic kinetics experiments. The binding kinetic parameters of xanthine oxidase and potential inhibitor in Ch. morifolium were determined by surface plasma resonance(SPR). The verified mathematical model of the XOD target occupancy evaluated the kinetic binding process of inhibitors and xanthine oxidase in vivo. According to UPLC-Q-Exactive MS and reference substance identification, 39 potential uric acid-lowering active ingredients in Ch. morifolium extracts were identified and the inhibitory activities of 23 compounds were determined. Three potential xanthine oxidase inhibitors were screened, namely genistein, luteolin, and apigenin. whose IC_(50 )were 1.23, 1.47 and 1.59 μmol·L~(-1), respectively. And the binding rate constants(K_(on)) were 1.26×10~6, 5.23×10~5 and 6.36×10~5 mol·L~(-1)·s~(-1), respectively. The dissociation rate constants(K_(off)) were 10.93×10~(-2), 1.59×10~(-2), and 5.3×10~(-2 )s~(-1), respectively. After evaluation by different administration methods, the three selected compounds can perform rapid and sustained inhibition of xanthine oxidase in vivo under combined administration. This study comprehensively evaluated the target occupancy process of three effective components in different ways of administration in vivo by UPLC-MS, concentration-response method, SPR technology and xanthine oxidase target occupancy model, which would provide a new research idea and method for screening active ingredients in traditional Chinese medicine.

Simulation Analysis of Occupancy Rates of Baicalein， Quercetin and Galangin on Target Sites of Xanthine Oxidase / 中国实验方剂学杂志

Objective:To simulate the occupancy rates of baicalein， quercetin and galangin on the target sites of xanthine oxidase <italic>in vivo</italic>. Method:In this experiment， the half inhibitory concentration （IC₅₀） of febuxostat， baicalein， quercetin and galangin against xanthine oxidase were determined by <italic>in vitro</italic> enzymatic reaction. Binding free energy was predicted by molecular docking technology and their association rate constant （k_on） and dissociation rate constant （k_off） were determined by surface plasmon resonance technology. Based on measured binding kinetic parameters （k_on and k_off） and extracted pharmacokinetic data， the target occupancy model <italic>in vivo</italic> was established. Result:The IC₅₀values of febuxostat， baicalein， quercetin and galangin were 0.002 7， 1.63， 0.38， 1.59 µmol·L^-1， respectively. The IC₅₀ of febuxostat was very close to that reported in the literature. The predicted curve of target occupancy rate <italic>in vivo</italic> of febuxostat was consistent with its duration of clinical efficacy. When single intragastric administration of long-circulating liposomes of quercetin with dose of 100 mg·kg^-1 in rats， the time of target occupancy rate >70% <italic>in vivo</italic> lasted for about 3.9 h. When rats were orally administered baicalein and galangin with dose of 200 mg·kg^-1， the time of target occupancy rate >50% <italic>in vivo </italic>lasted for about 10 h and 1.7 h， respectively. Conclusion:The prediction model of xanthine oxidase target occupancy constructed by drug target binding kinetics and <italic>in vivo</italic> pharmacokinetic curves can effectively evaluate the <italic>in vivo</italic> inhibitory activity of compounds against the target.

Mitochondrial oxidative damage and apoptosis induced by high glucose through Rho kinase signal pathway in renal tubular epithelial cells

Objective:To investigate the role of oxidative stress in human renal tubular epithelial cells (HK-2) induced by high glucose and the underlying signal pathway in vitro.Methods:MYPT1, pro-caspase-3, PGC-1α, and Drp1 protein expressions were measured by Western blot. MnSOD2, Drp1 and PGC-1α mRNA expressions were detected by real time PCR.Results:Results showed that high glucose significantly up-regulated the protein expressions of MYPT1, pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells; while Rho kinase inhibitor fasudil and ROCK1 siRNA inhibited protein expressions of pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells induced by high glucose. Importantly, fasudil and ROCK1 siRNA markedly inhibited the expressions of mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α in HK-2 cells induced by high glucose.Conclusions:Our findings suggest that Rho kinase signal pathway is involved in mitochondrial oxidative damage and apoptosis in high glucose-induced renal tubular epithelial cells by regulating mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α. Targeting Rho kinase signal pathway might be a potential strategy for the treatment of diabetic nephropathy.

Improving teaching effects of medical image processing by research / 医疗卫生装备

Objective To improve the teaching effects of medical image processing.Methods Teaching content was reformed considering the problems encountered during clinical practice and research. Modern teaching methods such as problem-based learning and flipped classroom were adopted. In addition, professors from world famous Universities were invited to teach lessons.A website was also built for this course.Moreover,the students were encouraged to participate in after-class research.Finally,a new practice-based teaching mode with characteristic content and modern methods was developed.By adopting information technology,all-round students could be gifted with international vision.Results The students'interest was stimulated and their problem solving skills were improved.Conclusion The teaching effects of medical image processing can be largely improved by research,so that the students can not only master the course content well but also develop skills to solve practical problems.

Mitochondrial oxidative damage and apoptosis induced by high glucose through Rho kinase signal pathway in renal tubular epithelial cells

Objective: To investigate the role of oxidative stress in human renal tubular epithelial cells (HK-2) induced by high glucose and the underlying signal pathway in vitro. Methods: MYPT1, pro-caspase-3, PGC-1α, and Drp1 protein expressions were measured by Western blot. MnSOD2, Drp1 and PGC-1α mRNA expressions were detected by real time PCR. Results: Results showed that high glucose significantly up-regulated the protein expressions of MYPT1, pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells; while Rho kinase inhibitor fasudil and ROCK1 siRNA inhibited protein expressions of pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells induced by high glucose. Importantly, fasudil and ROCK1 siRNA markedly inhibited the expressions of mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α in HK-2 cells induced by high glucose. Conclusions: Our findings suggest that Rho kinase signal pathway is involved in mitochondrial oxidative damage and apoptosis in high glucose-induced renal tubular epithelial cells by regulating mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α. Targeting Rho kinase signal pathway might be a potential strategy for the treatment of diabetic nephropathy. http://www.apjtm.org/article.asp?issn=1995-7645;year=2018;volume=11;issue=6;spage=399;epage=404;aulast=Li;type=2.

Follistatin-Like 1 Promotes Bleomycin-Induced Pulmonary Fibrosis through the Transforming Growth Factor Beta 1/Mitogen-Activated Protein Kinase Signaling Pathway / 中华医学杂志(英文版)

Background@#Follistatin-like 1 (FSTL1) is a novel profibrogenic factor that induces pulmonary fibrosis (PF) through the transforming growth factor-beta 1 (TGF-β1)/Smad signaling. Little is known about its effects on PF through the non-Smad signaling, like the mitogen-activated protein kinase (MAPK) pathway. Therefore, this study aimed to investigate the role of FSTL1 in PF through the MAPK signaling pathway and its mechanisms in lung fibrogenesis.@*Methods@#PF was induced in Fstl1and wild-type (WT) C57BL/6 mice with bleomycin. After 14 days, the mice were sacrificed, and lung tissues were stained with hematoxylin and eosin; the hydroxyproline content was measured to confirm PF. The mRNA and protein level of FSTL1 and the change of MAPK phosphorylation were measured by quantitative polymerase chain reaction and Western blotting. The effect of Fstl1 deficiency on fibroblasts differentiation was measured by Western blotting and cell immunofluorescence. MAPK signaling activation was measured by Western blotting in Fstl1 and WT fibroblasts treated with recombinant human FSTL1 protein. We pretreated mouse lung fibroblast cells with inhibitors of the extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal kinase (JNK) signaling and analyzed their differentiation, proliferation, migration, and invasion by Western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis, and transwell assays. The Student's t-test was used to compare the differences between two groups.@*Results@#Fstl1 deficiency attenuated phosphorylation of the ERK, p38, and JNK signaling in bleomycin-induced fibrotic lung tissue 14 days after injury (0.67 ± 0.05 vs. 1.22 ± 0.03, t = 14.92, P = 0.0001; 0.41 ± 0.01 vs. 1.15 ± 0.07; t = 11.19; P = 0.0004; and 0.41 ± 0.01 vs. 1.07 ± 0.07, t = 8.92, P = 0.0009; respectively), compared with WT lungs at the same time and in primary lung fibroblasts (0.82 ± 0.01 vs. 1.01 ± 0.04, t = 4.06, P = 0.0150; 1.04 ± 0.03 vs. 1.24 ± 0.03, t = 4.44, P = 0.0100; and 0.76 ± 0.05 vs. 0.99 ± 0.05, t = 4.48, P = 0.0100; respectively), compared with TGF-β1-stimulated WT group. Recombinant human FSTL1 protein in lung fibroblasts enhanced TGF-β1-mediated phosphorylation of the ERK (1.19 ± 0.08 vs. 0.55 ± 0.04, t = 6.99, P = 0.0020), p38 (1.18 ± 0.04 vs. 0.66 ± 0.03, t = 11.20, P = 0.0020), and JNK (1.11 ± 0.01 vs. 0.84 ± 0.04, t = 6.53, P = 0.0030), compared with the TGF-β1-stimulated WT group. Fstl1-deficient fibroblasts showed reduced alpha-smooth muscle actin (α-SMA) expression (0.70 ± 0.06 vs. 1.28 ± 0.11, t = 4.65, P = 0.0035, compared with the untreated WT group; 1.40 ± 0.05 vs. 1.76 ± 0.02, t = 6.31, P = 0.0007; compared with the TGF-β1-treated WT group). Compared with the corresponding condition in the control group, the TGF-β1/FSTL1-mediated α-SMA expression was significantly suppressed by pretreatment with an inhibitor of p38 (0.73 ± 0.01 vs. 1.13 ± 0.10, t = 3.92, P = 0.0078) and JNK (0.78 ± 0.03 vs. 1.08 ± 0.06, t = 4.40, P = 0.0046) signaling. The proliferation of mouse lung fibroblast cells (MLgs) significantly decreased after treatment of an inhibitor of p38 (0.30 ± 0.01 vs. 0.46 ± 0.03, t = 4.64, P = 0.0009), JNK (0.30 ± 0.01 vs. 0.49 ± 0.01, t = 12.84, P = 0.0001), and Smad2/3 (0.18 ± 0.02 vs. 0.46 ± 0.02, t = 12.69, P = 0.0001) signaling compared with the dimethylsulfoxide group. The migration and invasion cells of MLgs significantly decreased in medium pretreated with an inhibitor of p38 (70.17 ± 3.28 vs. 116.30 ± 7.11, t = 5.89, P = 0.0042 for the migratory cells; 19.87 ± 0.84 vs. 32.70 ± 0.95, t = 10.14, P = 0.0005 for the invasive cells), JNK (72.30 ± 3.85 vs. 116.30 ± 7.11, t = 5.44, P = 0.0056 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ± 0.95, t = 11.00, P = 0.0004 for the invasive cells), and Smad2/3 (64.76 ± 1.41 vs. 116.30 ± 7.11, t = 7.11, P = 0.0021 for the migratory cells; 18.03 ± 0.94 vs. 32.70 ± 0.95, t = 13.29, P = 0.0002 for the invasive cells) signaling compared with the corresponding condition in the dimethylsulfoxide group.@*Conclusion@#FSTL1 affects lung fibroblast differentiation, proliferation, migration, and invasion through p38 and JNK signaling, and in this way, it might influence the development of PF.

Analysis of volatile organic compounds in water supply system of Minhang District of Shanghai / 复旦学报（医学版）

Objective To investigate the pollution status of volatile organic compounds (VOCs) in water supply systems of Minhang District of Shanghai taking Huangpu River and Qingcaosha reservoir as water source.Methods A total of 126 water samples were collected from water supply system for residents in Minhang District in Feb.(dry season) and Aug.(wet season) of 2016,including source water from Huangpu River and Qingcaosha reservoir,the factory finished water and tap water.Purge and trap gas chromatography mass spectrometry was used for the qualitative and quantitative determination of 86 kinds of VOCs.Results Totally,32 and 28 kinds of VOCs were detected in the water supply systems from the Huangpu River and Qingcaosha reservoir,among which 19 and 21 pollutants were priority-controlled by the US EPA,and 18 and 14 species have the national standard in China separately.The concentration of detected pollutants ranged from 0.04 μg/L to 213μg/L and from 0.04μg/L to 728μg/L,respectively.The pollutants in the supply system of the Huangpu river were at the lower level except for methyl tert-butyl ether (MTBE).The pollutants in the supply system of Qingcaosha reservoir were lower than the national standards in addition to dichloromethane and 1,2-dichloroethane,and with the higher level of Methyl chloride and MTBE.In both water supply systems,halogenated aliphatic hydrocarbons and aromatic compounds were mainly types of VOCs,but there were varied types and quantities of compounds in each water supply system.The halogenated aliphatic hydrocarbons accounted for 37.5％ and 56.2％ of the detected VOCs respectively,while aromatic compounds accounted for 64.3％ and 28.6％.A total of 5 disinfection by-products (DBP) were detected in both water supply systems,but the concentrations of dichloromethane,chloroform,bromodichloromethane and dibromochloromethane in the Qingcaosha reservoir water supply system were significantly higher than those in the Huangpu River water supply system,except for bromoform.The concentration of the disinfection by-products in order from large to small were in the tap water,factory finished water and source water,while dichloromethane was an exception.Conclusions There were VOC pollutions in both water supply system in Minhang District,including source water,factory finished water and tap water,with different pollution characteristics.Adequate attention should be paid to the pollutants without national standards in the future water quality monitoring work.

Analysis of volatile organic compounds in water supply system of Minhang District of Shanghai / 复旦学报（医学版）

Objective To investigate the pollution status of volatile organic compounds (VOCs) in water supply systems of Minhang District of Shanghai taking Huangpu River and Qingcaosha reservoir as water source.Methods A total of 126 water samples were collected from water supply system for residents in Minhang District in Feb.(dry season) and Aug.(wet season) of 2016,including source water from Huangpu River and Qingcaosha reservoir,the factory finished water and tap water.Purge and trap gas chromatography mass spectrometry was used for the qualitative and quantitative determination of 86 kinds of VOCs.Results Totally,32 and 28 kinds of VOCs were detected in the water supply systems from the Huangpu River and Qingcaosha reservoir,among which 19 and 21 pollutants were priority-controlled by the US EPA,and 18 and 14 species have the national standard in China separately.The concentration of detected pollutants ranged from 0.04 μg/L to 213μg/L and from 0.04μg/L to 728μg/L,respectively.The pollutants in the supply system of the Huangpu river were at the lower level except for methyl tert-butyl ether (MTBE).The pollutants in the supply system of Qingcaosha reservoir were lower than the national standards in addition to dichloromethane and 1,2-dichloroethane,and with the higher level of Methyl chloride and MTBE.In both water supply systems,halogenated aliphatic hydrocarbons and aromatic compounds were mainly types of VOCs,but there were varied types and quantities of compounds in each water supply system.The halogenated aliphatic hydrocarbons accounted for 37.5％ and 56.2％ of the detected VOCs respectively,while aromatic compounds accounted for 64.3％ and 28.6％.A total of 5 disinfection by-products (DBP) were detected in both water supply systems,but the concentrations of dichloromethane,chloroform,bromodichloromethane and dibromochloromethane in the Qingcaosha reservoir water supply system were significantly higher than those in the Huangpu River water supply system,except for bromoform.The concentration of the disinfection by-products in order from large to small were in the tap water,factory finished water and source water,while dichloromethane was an exception.Conclusions There were VOC pollutions in both water supply system in Minhang District,including source water,factory finished water and tap water,with different pollution characteristics.Adequate attention should be paid to the pollutants without national standards in the future water quality monitoring work.

Snitrosylating protein disulphide isomerase mediates increased expression of α synuclein caused by methamphetamine in mouse brain / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of Snitrosylation of protein disulphide isomerasec in methamphetamine (METH)-induced expression of alpha synuclein (αSN) in mouse hippocampus and striatum neurons.</p><p><b>METHODS</b>Forty C57BL/6 mice were randomized equally into saline control group, METH group, L-NNA (a NOS inhibitor) group and L-NNA plus METH group. All the agents were injected intraperitoneally at an interval of 12 h, and a total of 8 injections were administered; in L-NNA plus METH group, METH was injected 30 min after LNNA in each treatment. Western Blotting was used to detect the expression of nitric oxide synthase (NOS), αSN, PDI and Snitrosylation of protein disulphide isomerase (PDI-SNO) in the hippocampus and striatum of the mice, and nitric oxide (NO) levels were determined using a NO assay kit.</p><p><b>RESULTS</b>In METH group, the levels of NOS, PDISNO, αSN and NO all increased significantly compared with those in the control group (P<0.05). Combined treatment with L-NNA and METH, compared with METH alone, resulted in significantly lowered expression of NOS, NO, PDI-SNO and αSN in the hippocampus and striatum of the mice (all P<0.05). No significant differences were found in NOS, NO, PDI-SNO or αSN expressions among METH+L-NNA, L-NNA and control groups (P>0.05).</p><p><b>CONCLUSION</b>METH induces the activation of NOS and increases NO level to cause the occurrence of PDI-SNO, leading subsequently to increased expression of αSN in mouse striatum and hippocampus. L-NNA, the inhibitor of NOS, can partly relieve nervous system toxicity induced by METH.</p>

Evaluation for impacts of gut wall metabolism of multiple components in Chuanxiong Rhizoma during intestinal absorption with S9 incubation / 中国中药杂志

The information of drug deposition in the intestine is required in the study for the drug absorption in biopharmaceutics classification system (BCS). To illustrate the impacts of gut wall metabolism on the absorption, metabolism of multiple components in Chuanxiong Rhizoma in gut wall was tested by rat S9 incubation in vitro. The chemical fingerprint technology was used in this study to simultaneously detect multiple components in Chuanxiong, and peak areas before and after S9 incubation were compared. The results showed that senkyunolide I and several constituents were metabolized by gut wall, and one new metabolite was founded. However, ferulic acid and other compounds remained unchanged after incubation. Therefore, the subsequent intestinal permeability of multiple components in Chuanxiong that were not metabolized in the intestine was suggested to be detected directly by in situ single-pass intestinal perfusion (SPIP).Nonetheless, the intestinal permeability of the constituents that were metabolized in the intestine shall be explored by appropriate approaches.

AEG-1 participates in high glucose-induced activation of Rho kinase and epithelial-mesenchymal transition in proximal tubular epithelial cells

Objective: To prove whether astrocyte elevated gene-1 (AEG-1) plays a role in high glucose-stimulated Rho kinase activation and epithelial-mesenchymal transition (EMT) in human renal tubular epithelial (HK-2) cells. Methods: The protein levels of AEG-1, alpha-smooth muscle actin, E-cadherin and MYPT1 were determined by Western blot. Results: AEG-1 protein level was upregulated in HK-2 cells stimulated with high glucose. AEG-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced EMT. Conclusions: Our results show that AEG-1 acts a key role in high glucose-induced activation of Rho kinase and EMT in HK-2 cells.

AEG-1 participates in high glucose-induced activation of Rho kinase and epithelial-mesenchymal transition in proximal tubular epithelial cells

OBJECTIVE@#To prove whether astrocyte elevated gene-1 (AEG-1) plays a role in high glucose-stimulated Rho kinase activation and epithelial-mesenchymal transition (EMT) in human renal tubular epithelial (HK-2) cells.@*METHODS@#The protein levels of AEG-1, alpha-smooth muscle actin, E-cadherin and MYPT1 were determined by Western blot.@*RESULTS@#AEG-1 protein level was upregulated in HK-2 cells stimulated with high glucose. AEG-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced EMT.@*CONCLUSIONS@#Our results show that AEG-1 acts a key role in high glucose-induced activation of Rho kinase and EMT in HK-2 cells.

Relation of MBL ExonI 54 and NFκB1-94ins/del ATTG Polymorphism with Fever during Neutropenia in Patients with Acute Leukaemia after Chemotherapy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the correlation between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia (AL) (except M3) after first chemotherapy in Chinese Han population.</p><p><b>METHODS</b>Blood samples obtained from 76 fever patients with AL during neutropenia episodes were detected to analyse single nucleotide polymorphism (SNP) in the MBL ExonI 54 and NFκB1-94ins/del ATTG gene, and analyse the correlation between above-mentioned 2 polymorphisms and fever during neutropenia of AL patients after chemotherapy.</p><p><b>RESULTS</b>In 76 patients, no correlation were found between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia after chemotherapy (P > 0.05). No significant relation were found in sex, age, underlying disease, disease status or degrees of neutropenia in febrile neutropenia between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism (P > 0.05). However, patients with MBL ExonI 54 mutation presented longer febrile duration with a median of 5 days compared to 3 days of patients with wildtype MBL ExonI 54 genotype (P < 0.05).</p><p><b>CONCLUSIONS</b>There is no clear correlation between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia after chemotherapy. However, the patients with MBL ExonI 54 mutation have been observed to present a longer febrile duration.</p>

Study of attribution of multicomponent original medicinal materials in gegen qinlian decoction with intestinal permeability / 中国中药杂志

The complex level of constructing biopharmaceutics classification system of Chinese materia medica CMMBCS) was the study of traditional Chinese compound, on the premise of insisting that the multicomponent simultaneous determination, when carrying out the study of intestinal permeability, the primary task was to define the source of the components that was absorbed through the intestinal wall, namely, which medicinal material the components belonged to in traditional Chinese compound. The technology of chemical fingerprint and in vitro everted gut sac model were used in this research to make multicomponent an intuitive source attribution which permeated the intestine in the classic formula Gegen Qinlian decoction, and to lay the foundation for the further qualitative and quantitative research of intestinal permeability.

Impacts of multicomponent environment on solubility of puerarin in biopharmaceutics classification system of Chinese materia medica / 中国中药杂志

To illustrate the solubility involved in biopharmaceutics classification system of Chinese materia medica (CMMBCS) , the influences of artificial multicomponent environment on solubility were investigated in this study. Mathematical model was built to describe the variation trend of their influence on the solubility of puerarin. Carried out with progressive levels, single component environment: baicalin, berberine and glycyrrhizic acid; double-component environment: baicalin and glycyrrhizic acid, baicalin and berberine and glycyrrhizic acid and berberine; and treble-component environment: baicalin, berberin, glycyrrhizic acid were used to describe the variation tendency of their influences on the solubility of puerarin, respectively. And then, the mathematical regression equation model was established to characterize the solubility of puerarin under multicomponent environment.

Analysis of monitoring results of urinary iodine levels of 5 special groups in Ningxia / 中国地方病学杂志

Objective To investigate the iodine nutritional level of 5 special groups (newly married women,pregnant women, lactating women, babies and infants, and students) in Ningxia, and to provide the basis for formulating prevention and control strategies. Methods Clustering and random sampling method were used. In 2008 and 2009, in the 22 counties investigated, in every county with 9 townships or more, nine townships were randomly selected according to their sub-area positions of east, west, south, north and center; four villages were randomly selected in each chosen township, four people with special needs and 2 infants were randomly selected for urine samples collection in each chosen village. In every county with 9 or less townships, one township was randomly selected respectively in east, west, south, north and center sub-areas; four villages were randomly sampled in each chosen township, eight people with special needs and 3 infants' urine samples were randomly collected in each chosen village. In the 22 counties, one township was randomly selected respectively in east, west,south, north and center sub-areas, one village elementary school was randomly sampled in each chosen township,twenty students aged 8 - 10 were randomly selected to collect their urine samples in each school. The iodine concentration was determined by arsenic-cerium contact method. Results A total of 6894 copied of urine samples from newly married women, pregnant women, lactating women, babies and infants, and students were examined, the urinary iodine medians were 209.3, 187.4, 184.0, 216.5, 216.3 μg/L, respectively. From low to high in the order was lactating women, pregnant women, newly married women, students, babies and infants. The level of urinary iodine of babies and infants, pregnant women and lactating women were appropriate, the one of newly married women and students were higher than appropriate. The proportion of less than 100 μg/L of urinary iodine of the 5 kinds special groups were 11.1% (53/475), 35.4% (308/871), 35.4% (659/1863), 19.1% (283/1483), 8.4%(185/2202), respectively, while the urinary iodine of the pregnant women and lactating women were relatively high. The urinary iodine medians of the 5 special groups were also very different among counties. Conclusions The urinary iodine of the 5 special groups in Ningxia presents obvious differences between populations and regions.Current iodized salt is sufficient to ensure iodine nutrition needs for the 5 special groups. But married women and students have higher levels of iodine nutrition, indicating that the salt iodine concentration of Ningxia residents have cut space, full consideration of the 5 special groups and regional differences should be taken.

Statistical analysis of monitoring data regarding urinary iodine level of infants and babies in Ningxia in 2009 / 中国地方病学杂志

Objective To determine urinary iodine level among babies and infants aged 0-30 months in Ningxia, and to provide scientific evidence for strengthening iodine supplement or decreasing salt iodine level in special population. Methods One thousand four hundred and eighty-three babies and infants were selected randomly from 664 administrative villages of 22 counties (city or district) by two-stage sampling method. Urinary iodine was tested with the arsenic cerium catalysis spectrophotometric method and related influencing factors were analyzed. Results Urinary iodine median was 216.5 μg/L of the whole autonomous region, and the value that was lower than 100 μg/L, accounted for 19.1%(283/1483), 100 - 300 μg/L accounted for 49.3%(731/1483), higher than 300 μg/L, accounted for 31.6% (469/1483). Urinary iodine median was in 130.6 - 328.4 μg/L of all counties, which was higher than 100 μg/L. The urinary iodine median of men(223.2 μg/L) was slightly higher than that(210.2 μg/L) of female, no significant difference was observed(Z = - 1.76, P > 0.05). Urinary iodine level changed little when child was younger than one year old(Z = - 0.624, P > 0.05). Then the value dropped gradually after one year old(χ2 = 13.59, P < 0.05), decreased with age by month, and the proportion of the value smaller than 100 μg/L was increased gradually. Urinary iodine level(257.5 μg/L) of child whose mother had taken iodine oil pills was higher than that (221.2 μg/L) of child whose mother had significant difference was observed(Z = - 2.54, P < 0.05). The urinary iodine level (239.1 μg/L) of child who received breast feeding was higher than that (204.2 μg/L) of child without breast feeding among one year old and younger infants and babies, significant difference was observed (Z = - 2.74, P < 0.05). Conclusions Current iodine level in iodized salt is probably higher than suitable in Ningxia, and the value could be decreased. It is unnecessary to strengthen iodine supplement procedure in special population other than people in Xiji county.

Fosinopril up-regulates and ameliorates the Ang II induced down-expression of klotho gene in NRK-52E / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of fosinopril (Fos) on regulating klotho gene expression and elucidate the mechanism of Fos regulating the Angiotensin II (AngII) -induced down-expression of klotho gene.</p><p><b>METHODS</b>Culture cells, NRK-52E, were incubated with media either AngII or Fos or both of all. Experimental groups incubated with Fos (10(-5) mol/L) were divided according to variant points of time for 0 (control), 3, 6, 12, 24 h. Different concentration of Fos was selected to incubated with culture cells for 0 (control), 10(-9) 10(-8), 10(-7), 10(-6), 10(-5) mol/L at the optimal time point (24 h). Five groups, which were A: control; B: AngII (10(-7) mol/L); C: Fos(10(-5) mol/L); D: AngII (10(-7) mol/L) + Fos(10(-5) mol/L) and E: Cells pretreated with Fos(10(-5) mol/L)12 h incubated with AngII (10(-7) mol/L) were divided to observe the effect of Fos on expression of klotho induced by AngII. RT-PCR and immunohistochemistry (IHC) were applied to evaluate the klotho mRNA and protein expression, respectively.</p><p><b>RESULTS</b>Fos up-regulated klotho mRNA in time-dependent manner, and independent of dose-dependent manner; AngII obviously decreased the levels of kloltho mRNA and protein expression in NRK-52E as compared to the control (P < 0.05), the down-regulating effect was reversed by incubating both with AngII and Fos (P < 0.05), and Fos could inhibit the down-regulated expression of klotho gene induced by Ang II in NRK-52E.</p><p><b>CONCLUSION</b>Fosinopril up-regulates klotho mRNA in time-dependent manner, and inhibits the down-regulated expression of klotho gene induced by Ang II.</p>

Expression of fusion protein encoding EGFP-EGF1 of rat coagulation factor VII and its binding function / 中国实验血液学杂志

This study was aimed at clarification of the function of EGF(1) segment in rat coagulation factor VII with tissue factor (TF) by means of the expression of the fusion protein of EGFP-EGF(1). The DNA fragment encoding EGF(1) was amplified from a rat liver tissue by RT-PCR, and then inserted in an EGFP-procaryotic expression vector to construct the recombinant plasmid pET28a-EGFP-EGF(1) which was introduced into the competent cells of E.coli BL21, then an engineering bacteria strain was obtained which was induced by IPTG to express the fusion protein of EGFP-EGF(1). The fusion protein was purified by chromatography on Ni column, and then acted on the rat hemangioendotheliocytes stimulated with LPS to express TF; the binding of the fusion protein to the hemangioendotheliocytes was detected by means of fluorescence microscopy and flow cytometry. The results indicated that EGFP-EGF(1) was highly expressed in the engineering E.coli strain, and successfully purified, and its molecular mass was confirmed as 36 kD by SDS-PAGE. Fluorescence microscopy and flow cytometry had shown that this fusion protein can bind with the TF on the hemangioendotheliocytes. It is concluded that the EGF(1) region of rat coagulation factor can mediate the specific binding of FVII with TF, so as to lay partly the basis for molecular targeting anti-thrombotic therapy.

Effects of arsenic trioxide or retinoic acid on mRNA and protein expression of tissue factor and thrombomodulin and procoagulant activity in NB4 cells / 中国实验血液学杂志

To investigate the effect of arsenic trioxide (As(2)O(3)) or all-trans retinoic acid (ATRA) on the mRNA and protein expression of tissue factor (TF) and thrombomodulin (TM) and procoagulant activity (PCA) in NB4 cells. The NB4 cells were cultured in vitro and treated with As(2)O(3) or ATRA, expression of TF and TM antigen, and PCA change of treated NB4 cells were detected with ELISA, TF and TM mRNA transcription on the NB4 cells was assayed with reversed transcription polymerase chain reaction (RT-PCR). The results showed that 1 micromol/L As(2)O(3) and 1 micromol/L ATRA both gradually downregulated the expression of TF antigen and mRNA on NB4 cells, a human promyelocytic leukemia cell line, in time-dependent manner, as compared with control. The levels of TF antigen expression in AS(2)O(3) group were 13.3 +/- 1.8, 8.6 +/- 1.9, 10.8 +/- 1.5, 2.0 +/- 0.6 and 2.6 +/- 0.9 ng/10(7) respectively; while the levels of TF antigen expression in ATRA group were 12.4 +/- 1.1, 11.3 +/- 1.8, 5.7 +/- 1.7, 2.8 +/- 0.8 and 2.0 +/- 0.6 ng/10(7) at 24, 48, 72, 96 and 120 hours respectively (P<0.05). The procoagulant activity (PCA) of NB4 cells was decreased, blood coagulation times were 123.5 +/- 10.5, 156.3 +/- 11.6, 179.3 +/- 15.3, 248.9 +/- 20.1, 312.0 +/- 29.8 seconds in As(2)O(3) groups, respectively; 76.4 +/- 5.6, 146.8 +/- 10.9, 198.2 +/- 15.6, 265.8 +/- 20.6 and 363.8 +/- 31.9 seconds in ATRA groups respectively at 24, 48, 72, 96 and 120 hours (P<0.05). ATRA upregulated TM antigen expression on NB4 cells. It is concluded that the As(2)O(3) and ATRA decrease mRNA transcription of TF, downregulate expression of TF and reduce procoagulant activity in NB4 cells. The TM transcription and expression upregulated by ATRA may alleviate dysfunction of coagulation in APL.