Synthesis, cholinesterase inhibition and hepatotoxicity of tacrine-phenol-bifendate hybrids / 药学学报

A series of tacrine-phenol-bifendate hybrids (7a-7e, 8a-8e) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs) with low hepatotoxicity. All the compounds had potent ChEs inhibitory activity with half-inhibitory concentration (IC50) values at the nanomolar range. Compound 8d exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC50 value of 156.39 nmol·L-1 and compound 7b showed the most potent inhibition for butyrylcholinesterase with IC50 value of 16.33 nmol·L-1. Kinetic and molecular modeling studies showed that 8d targeted both the catalytic active site and the peripheral anionic site of AChE. In addition, these compounds showed low toxicity to hepatocytes, and compound 8d did not increase the level of reactive oxygen species in HepG2 cells.

Designing of a portable arm bracket and its application in PICC placement / 中华护理杂志

Objective To design and apply a portable arm bracket for patients undergoing PICC placement and to solve the problem of raising and placing the arm during PICC placemen and promote comfort level.Methods Ninety-eight patients were provided with portable arm bracket between August and November in 2016 as the experimental group,82 patients were provided with wood board between April and July in 2016 as the control group.The comfort degree,placement success rate,number of multiple attempts to insert needle and advance guidewire,and case of abnormal events were compared between two groups.Results Level 1 comfort in the experimental group was higher than the control group,and level 2,3 and 4 comfort in the experimental group were lower than the control group,and differences were statistically significant (P＜0.001).Placement success rate of the experimental group(98.0％) was slightly higher than that of the control group(93.9％),but the difference was not statistical significant (P=0.31).The number of multiple attempts to insert needle and advance guidewire in the experimental group was lower than the control group,and the difference was statistically significant(P＜0.05).Abnormal events occurred in 3 cases in the experimental group and the incidence rate was 3.1％;there were 6 cases in the control group and the incidence rate was 7.3％.Conclusion The shelve and raising function of the portable arm bracket boost patients' catheter comfort degree,improve the success rate of catheterization and reduce the occurrence of complications cases.

Design, synthesis and evaluation of bis-nicotine derivatives as inhibitors of cholinesterases and beta-amyloid aggregation / 药学学报

A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).

Design, synthesis and evaluation of tacrine-methoxybenzene hybrids as cholinesterases inhibitors / 药学学报

A series of tacrine-methoxybenzene hybrids (5a-5i) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). All the compounds had better ChEs inhibitory activities than tacrine with IC50 values at the nanomolar range. Compound 5h exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 6.74 nmol x L(-1) and compound 5f showed the most potent inhibition on butyrylcholinesterase with IC50 value of 3.83 nmol x L(-1). Kinetic and molecular modeling studies showed that these hybrids targeted both the catalytic active site and the peripheral anionic site of AChE.

Expression and clinical significance of IL-17 and IL-21 in patients with acute leukemia / 中国实验血液学杂志

This study was aimed to investigate the effects of peripheral blood Th17 cells, IL-17 and IL-21 in the occurrence and development of acute leukemia. 60 patients with acute leukemia (19 patients with ALL, 41 patients with AML) were divided into non-remission group (group A, n=24), remission group (group B, n=36); 25 healthy volunteers were used as control group (group C). In addition to this, these 60 patients were divided into infection group (n=32) and non-infection group (n=28) on the basis of infection status. The concentration of IL-17 and IL-21 in the peripheral blood mononuclear cell culture supernatant after stimulation with anti-CD3 and anti-CD28 mAb were determined with ELISA. The expression of CD4+ IL-17+ cells was determined by flow cytometry. The results showed that (1) the concentrations of IL-17 and IL-21, and proportion of Th17 cells in group A and group B were much lower than those in group C (p<0.05); (2) the expression levels of IL-17 and IL-21, and the proportion of Th17 cells in group A were lower than those in group B (p<0.05); (3) the expression levels of Th17 and IL-17 in infection group were lower than those in non-infection group (p<0.05). It is concluded that Th17 cells may play important roles in the occurrence and development of acute leukemia through secreting IL-17 and IL-21, and their functional level can partially reflect the status of leukemia and can be used to evaluate the risks of infection in patients with leukemia.

Perpetual impact of pregnancy-induced hypertension on blood pressure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the perpetual impact of pregnancy-induced hypertension on blood pressure.</p><p><b>METHODS</b>This retrospective cohort study included 782 cases of pregnant women who hospitalized at Kailuan Linxi hospital between October 1976 and August 2001. Patients were divided to with pregnancy induced hypertension (PIH, n = 77) group and non pregnancy induced hypertension (NPIH, n = 705) group. Patients were followed for 5 to 34 years (mean 18.8 +/- 5.3 years), the incidence of essential hypertension was obtained in July 2006-September 2007.</p><p><b>RESULTS</b>(1) The cumulative incidence of essential hypertension during follow up was significantly high in PIH group (29.87%) than that in NPIH group 18.87% (P = 0.022). (2) At the final follow up, waist circumference; [(86.06 +/- 10.15) cm vs. (83.07 +/- 8.19) cm, P = 0.015], BMI [(24.83 +/- 4.01) kg/m(2) vs. (23.50 +/- 3.39) kg/m(2), P = 0.006], TC [(5.11 +/- 0.88) mmol/L vs. (4.89 +/- 0.94) mmol/L, P = 0.045] and GLU [(5.57 +/- 1.78) mmol/L vs. (5.20 +/- 1.38) mmol/L, P = 0.010] were all significantly higher in PIH group than those in NPIH group. (3) After adjustment of age and BMI, PIH was still significantly correlated with long-term systolic blood pressure levels (P = 0.048), fasting glucose level was also significantly associated with long-term systolic blood pressure. Age, BMI, white blood cell count and uric acid were also predictors for perpetual systolic and diastolic blood pressure levels.</p><p><b>CONCLUSIONS</b>Incidence of essential hypertension in women with PIH was higher than that in women without PIH. After adjustment of covariates including age, BMI, and glucose, PIH was significantly associated with the level of systolic blood pressure. BMI, fasting glucose and cholesterol levels might contribute to the increase of systolic blood pressure in patients with PIH.</p>

Analysis on the feasibility in determination of salt iodine content of Sichuan with oxidation-reduction titration / 中国地方病学杂志

Objective To investigate the influential factors and the control measures thereof iodine salt detection with oxidation-reduction titration method so as to improve the detection quality.Methods 122 samples were obtained randomly from four counties(districts)of Sichuan Province to determine iodine ions forms.In center for diseases control and prevention(CDC)laboratories at the provincial and county levels,iodine contents in the samples were determined with oxidation-reduction titration and the results were compared between laboratories.The provineial lahoratory also employed bromine water oxidation for method comparison.Also the volume fractions of chlorine available were determined in sodium hypochlorite storage in open or sealed status and of different storage periods of 1,2,4,7,14,30 and 60 days.Results The iodine transformed from 103- to I-during the shipment and storage;The iodine contents in the 122 salt samples determined by the laboratories at the provincial and county levels were respectively(32.40±8.44),(31.10±8.34)mg/kg with a result discrepancy of 1.33 mg/kg.Of all the absolute discrepancy values,18.8%(23/122)were lower than or equal to 1 mg/kg;23.0%(28/122)were equal to or higher than 3 mg/kg;23.0%(28/122)were lower than or equal to 5 mg/kg;26.2%(32/122)were lower than or equal to 10 mg/kg;9.0%(11/122)were higher than 10 mg/kg.After the botdes were opened and stood for 60 days,the available chlorine content in the sodium hypochlorite decreased by 43.6%and 32.5%respectively in open and sealed status,Iodine contents were respectively(32.60±8.44),(32.50±8.18)mg/kg(n=114)with the oxidationreduction titration method and bromine water oxidation method,and no significant difierence was found between the results of the two methods(t=0.282,P＞0.05).Conclusions Potassium iodate in salt in Sichuan is Dmne to transform into potassium iodide during shipping,so when determining salt iodine with the oxidation-reduction titration method,the content and the amount of chlorine available in the sodium hypochlorite differ a lot and are difficult to control.Therefore.bromine water oxidation titration is recommended.

Synthesis and antitumor activity of benzoic nitrogen mustard derivatives / 药学学报

To study the effect of isoprenoid and aliphatic saturated alcohols as modificator on benzoic nitrogen mustard, the intermediate 4-[N,N-bis(2-chloroethyl) amino] benzoic acid 4 was prepared in four steps utilizing p-amino benzoic acid as the starting material. Target compounds were synthesized by the catalytic esterification of DCC/DMAP and the structures of the six new esters were characterized by elemental analysis, 1H NMR, 13C NMR and MS. Antitumor activities were evaluated in vitro using MTT assay. The result showed that some derivatives were more potent than the intermediate 4, and compound 5c modified with dodecanol exhibited similar activity to the commercial drug melphalan.

Apoptosis related changes in the brain of diabetic mice and the effect of amyloid precursor protein 17 mer peptide / 中国药理学通报

Aim: To investigate whether the changes of neuron apoptosis related proteins exist in the brain of diabetic mice and to observe the effects of β-amyloid precursor protein (APP) 17-mer peptide on these changes. Methods: Mouse diabetic model was produced with streptozotocin, and APP17-mer peptide was injected subcutaneously as a treatment. Four weeks later, brain slides of mice were studied by immunohistochemistry for Fas, Fas-L, NF-κB, Presenilin-1 (PS-1), α-Synuclein and by TUNEL to observe the DNA fragments of neurons. Results: Circled digit one The number of neurons stained positively by Fas, Fas-L, PS-1, α-Syn antibodies in the brain of diabetic mice increased. In contrast to diabetic mice the number of positively stained hippocampal cells in normal mice were markedly reduced. The result of APP17 mer peptide-treated mice was the same as that in normal mice. The hippocampal neurons of diabetic mice showed significant intracellular decrease in NFκB. Treatment with APP 17mer peptide normalizes the expression of NFκB in diabetic mice. Circled digit two There were very little apoptotic neurons stained by TUNEL in the hippocampus of the three groups. Conclusions: The apoptosis related protein changes exist in the brain of diabetic mice. APP17mer peptide can normalize the expression of apoptosis related proteins, indicating that APP17mer peptide can improve the apoptosis abnormalities of diabetic mice and retard neuronal degeneration.

Effect of aging on the expression of nitric oxide synthase I and the activity of nitric oxide synthase in the rat penis / 中华男科学杂志

<p><b>OBJECTIVES</b>To investigate the effect of aging on the expression of nitric oxide synthase I (NOS I) and the activity of nitric oxide synthase in the rat penis.</p><p><b>METHODS</b>Thirty male rats from three age groups(adult, old and senescent) were investigated: 1. The expressions of NOS I protein and mRNA in the penis were detected by Western blot and RT-PCR, respectively. 2. NOS activity in the penis was detected with ultraviolet spectrophotometry.</p><p><b>RESULTS</b>In rats of the old and the senescent groups, the expression of NOS I protein decreased significantly as compared to that of the adult group. NOS I mRNA expression was well related to its protein expression. NOS activity had no statistical difference between the adult group and the old group, but it reduced significantly in the senescent group as compared to that of the adult group(P < 0.01).</p><p><b>CONCLUSIONS</b>It is maybe one of the main mechanisms of erectile dysfunction in the aging male that the aging causes the decreases of NOS I protein and mRNA expression and NOS activity.</p>

Effect of aging on expression of nitric oxide synthase I and activity of nitric oxide synthase in rat penis / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate the effect of aging on the expression of nitric oxide synthase I (NOS I) and the activity of NOS in rat penis.</p><p><b>METHODS</b>Sixty male rats from 3 age groups (adult, old and senescent) were investigated. The expression of NOS I protein and mRNA in rat penis were detected by Western blot and RT-PCR respectively and the NOS activity, with ultraviolet spectrophotometry.</p><p><b>RESULTS</b>In the old and senescent group, NOS I protein expression was significantly decreased as compared with the adult. NOS I mRNA expression was well correlated with the protein expression. NOS activity was not statistically different between the adult and old groups, but it was significantly reduced in the senescent compared with the adult group (P<0.01).</p><p><b>CONCLUSION</b>The aging-induced decreases in NOS I expression and NOS activity may be one of the main mechanisms leading to erectile dysfunction in the senescent rats.</p>

Protein and mRNA expression of nitric oxide synthase isoforms I and III in rat penile spongium tissues / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate protein and mRNA expression of nitric oxide synthase (NOS) isoforms I and III in rat penile tissues.</p><p><b>METHODS</b>Penile tissues from male SD rats were investigated. The protein expression of NOS I and III in rat penis was confirmed by immunoprecipitation and Western blot. Gene expression of both NOS I and III was identified by reverse transcription-polymerase chain reaction.</p><p><b>RESULTS</b>The mRNA and protein products of NOS I and III are both expressed in normal rat penile spongium tissues. But, NOS III mRNA and protein products are more highly expressed than those of NOS.</p><p><b>CONCLUSIONS</b>These findings support the possibility that penile erection is regulated by different NOS isoforms in rat penile tissues.</p>