A novel hydrogen sulfide donor modulates Kir6.2 via the cyclic guanosine monophosphate- dependent protein kinase signaling pathway in one side hippocampus of epileptic rats / 中华神经科杂志

Objective:To explore the effect of hydrogen sulfide (H 2S) on modulating the subunit Kir6.2 of adenosine triphosphate sensitive potassium channels via the cyclic guanosine monophosphate-dependent protein kinase (cGMP/PKG) signaling pathway in epileptic rat models. Methods:Sixty adult male SD rats were randomly divided into the following six groups (10 rats in each group) by random number table method: control, epileptic, H 2S donor, H 2S donor+epileptic, KT5823 (one inhibitor of the cyclic guanosine monophosphate-dependent protein kinase)+H 2S donor+epileptic, and glibenclamide (one inhibitor of the adenosine triphosphate sensitive potassium channels)+H 2S donor+epileptic groups. Except the control group, SD rats were intraperitoneally injected with plentylenetetrazole to make the kindling models and their behaviours were recorded including the latency period, the grade, and the duration of the first epileptic seizure according to the Racine′s standard. The waveforms of electroencephalogram (EEG) in hippocampus were also recorded during the seizure. The mRNA and protein levels of PKG and Kir6.2 in hippocampus were evaluated by Western blotting and quantitative real-time polymerase chain reaction, and the hippocampal concentrations of cGMP and phosphorylation of cyclic guanosine monophosphate-dependent protein kinase (p-PKG) were detected by enzyme linked immunosorbent assay. Results:Rats in the epileptic group showed Ⅳ-Ⅴ grade of epileptic seizure [4.500 (4.000, 4.875)], short latency period [(10.37±8.21) min] but long duration [(69.50±24.37) s] of seizure. Compared to the epileptic group, rats in the H 2S donor group showed Ⅱ-Ⅲ grade of epileptic seizure ( P=0.004), significantly longer latency period ( P<0.001), and shorter duration of seizure ( P<0.001). Compared to the H 2S donor+epileptic group, rats in the KT5823+H 2S donor+epileptic group showed Ⅲ-Ⅳ grade of epileptic seizures, significantly shorter latency period ( P<0.001), and longer duration of seizure ( P<0.001). The results of EEG showed that the wave patterns in the epileptic group were spike or sharp waves and the amplitudes were largest [(190.570±23.590) μV]. Compared with the epileptic group, amplitudes were reduced ( P<0.001) in the H 2S donor+epileptic group. PKG mRNA and PKG protein were expressed differently among all groups (PKG mRNA: n=5, H=26.714, P<0.001; PKG protein: n=5, F=30.597, P<0.001). Compared with the control group, the expression of both PKG mRNA and PKG protein was decreased (PKG mRNA: 1.000±0.001 vs 0.782±0.064, P=0.023; PKG protein: 0.550±0.037 vs 0.145±0.020, P=0.042) in the epileptic group. Besides, Kir6.2 mRNA and Kir6.2 protein were expressed differently among all groups (Kir6.2 mRNA: n=5, H=27.761, P<0.001; Kir6.2 protein: n=5, F=60.659, P<0.001). Compared with the control group, the expression of both Kir6.2 mRNA and Kir6.2 protein was decreased (Kir6.2 mRNA: 1.000±0.001 vs 0.897±0.033, P=0.004; Kir6.2 protein: 0.384±0.035 vs 0.215±0.016, P=0.024) in the epileptic group. And the concentrations of cGMP and p-PKG were decreased (cGMP: P<0.001; p-PKG: P<0.001) in the epileptic group. The results in the H 2S donor+epileptic group were up-regulated (PKG mRNA: P=0.047; PKG protein: P<0.001; Kir6.2 mRNA: P=0.011; Kir6.2 protein: P<0.001; cGMP: P<0.001; p-PKG: P<0.001) compared with the epileptic group. However, the results in the KT5823+H 2S donor+epileptic group were down-regulated (PKG mRNA: P=0.015; PKG protein: P=0.027; Kir6.2 mRNA: P=0.013; Kir6.2 protein: P=0.017; cGMP: P=0.005; p-PKG: P<0.001) compared with the H 2S donor+epileptic group. Conclusion:A possible mechanism is that H 2S prevents the epileptic seizure from modulating the subunit Kir6.2 of ATP sensitive potassium channels via the cGMP/PKG signaling pathway.

Assessment of liver function of patients with HBV-related cirrhosis using T1 mapping on Gd-EOB-DTPA-enhanced MRI / 中华肝胆外科杂志

Objective To evaluate the value of T1 mapping in Gd-EOB-DTPA-enhanced MRI for the assessment of liver function with HBV-related cirrhosis according to the model for end-stage liver disease (MELD) score.Methods 158 patients with HBV-related cirrhosis were included in this prospective study,and divided into MELD score ≤10 (n =103) group and MELD score ＞ 10 (n =55) group.All patients un derwent non-enhanced and Gd-EOB-DTPA enhanced MRI of liver,and T1 mapping was performed using Look-Locker sequences with the same scan parameters and geometry position (the level of porta hepatis) preand post-contrast at 5,10,15 and 20 minutes after Gd-EOB-DTPA administration.T1 relaxation times of the liver were measured and reduction rates of T1 relaxation times (△T1) were calculated.Independent samples t test was performed to compare T1 relaxation times and △T1 between MELD score≤ 10 and MELD score ＞ 10 groups.Receiver operating characteristic curve (ROC) analysis were done to differentiate the diagnostic performance of T1 relaxation times and △T1 between MELD score ≤ 10 and MELD score ＞ 10 groups.Pearson correlation analysis was used to analyse the correction between T1 relaxation times,△T1 and MELD scores.Results T1 relaxation times pre-and post-contrast at 5,10,15 and 20 minutes and △T1 post-contrast at 5,10,15 and 20 minutes of MELD score≤10 group were (889.3 ±91.2) ms,(377.5 ± 55.0) ms,(350.8±61.2)ms,(328.0±69.4)ms,(302.7±73.7)ms,(57.4±5.6)％,(60.4± 6.5) ％,(63.0 ± 7.3) ％ and (65.9 ± 7.8) ％,respectively,and those of MELD score ＞ 10 group were (936.6 ±95.4) ms,(460.2 ±68.5) ms,(457.5 ±94.5) ms,(453.4 ± 116.4) ms,(444.6 ± 134.6) ms,(50.8 ± 5.7) ％,(51.3 ± 7.9) ％,(51.8 ± 10.3) ％ and (52.8 ± 12.2) ％,respectively,and T1 relaxation times and △T1 at all time points were significantly different (P ＜ 0.05) between the two groups.The areas under ROC curve of T1 relaxation time pre-and post-contrast at 5,10,15,20 minutes and △T1 post-contrast at 5,10,15,20 minutes for differentiating MELD score ≤ 10 and MELD score ＞ 10 groups were 0.638,0.824,0.832,0.832,0.830 and 0.795,0.814,0.820,0.825,respectively.The correlation coefficients between T1 relaxation time pre-and post-contrast at 5,10,15,20 minutes,△T1 post-contrast at 5,10,15,20 minutes and MELD scores were 0.256,0.499,0.540,0.538,0.548,-0.412,-0.495,-0.507 and-0.527,respectively.Conclusions T1 mapping on Gd-EOB-DTPA-enhanced MRI is helpful for evaluating liver function with HBV-related cirrhosis.T1 relaxation times post-contrast on different time points were equally accurate as △T1.T1 relaxation times post-contrast and △T1 were superior to T1 relaxation times pre-contrast.

Assessment of liver function using T1 mapping on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI / 中华放射学杂志

Objective To investigate the effectiveness of T1 mapping on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA-enhanced) MRI for the assessment of liver function.Methods One hundred and twenty six patients with clinically suspected focal liver lesions and chronic viral hepatitis B underwent MRI were prospectively enrolled.Patients were divided into four subgroups as follows: chronic viral hepatitis B (n=22), liver cirrhosis with Child-Pugh A (n=52), Child-Pugh B(n=41),Child-Pugh C(n=11).Twenty three healthy volunteers with normal liver function were enrolled as control group.Non-enhanced and Gd-EOB-DTPA enhanced MRI of liver were performed in all subjects.Look-Locker sequences with exactly the same scan parameters and geometry position(the level of porta hepatis) were performed pre and post-contrast separately at 5, 10, 15 and 20 minutes after Gd-EOB-DTPA administration.T1 relaxation times and reduction rates of T1 relaxation times[ΔT1(%)]of the liver parenchyma were measured and calculated.One-way ANOVA was used to compare T1 relaxation times and ΔT1(%) for control group, chronic viral hepatitis B group, liver cirrhosis with Child-Pugh A group, Child-Pugh B group,and Child-Pugh C group.ROC curve analysis was performed to compare the diagnostic performance of T1 relaxation times and ΔT1(%) values in discriminating control group + chronic viral hepatitis B group + liver cirrhosis with Child-Pugh A group from Child-Pugh B + C group. Results T1 relaxation times and ΔT1(%)showed significant difference(P<0.05)among control group and different liver function groups. T1 relaxation times and ΔT1(%) of both liver cirrhosis with Child-Pugh B group and Child-Pugh C group were significantly different(P<0.05)in comparison with those of control group,chronic viral hepatitis B group and liver cirrhosis with Child-Pugh A group at all time points.T1 relaxation times of the control group,chronic viral hepatitis B group,liver cirrhosis with Child-Pugh A group and Child-Pugh B group reduced with the scanning time increase,ΔT1(%)raised with the scanning time increase.T1 relaxation times progressively increased from control group to Child-Pugh C group at every time point.ΔT1(%)showed a constant decrease from control group to Child-Pugh C group at all time points.The areas under ROC curve of T1 relaxation time pre and post-contrast at 5,10,15 and 20 minutes for assessment of liver function were 0.817,0.952,0.950,0.946,and 0.949 respectively.The areas under ROC curve of ΔT1(%)post-contrast at 5, 10, 15 and 20 minutes for evaluation of liver function were 0.873, 0.876, 0.885, and 0.898, respectively. Conclusion Gd-EOB-DTPA-enhanced T1 mapping MRI is useful for the evaluation of liver function, and helpful for distinguishing patients with moderate and severe liver damage from normal and mild liver damage.

Chemical constituents of Viola yedoensis / 中草药

Objective To investigate the chemical constituents of the whole plants of Viola yedoensis. Methods The chemical constituents were isolated and purified by column chromatography over silica gel and Sephadex LH-20, as well as on the semi-preparative HPLC. The structures of the isolates were identified by the NMR spectroscopic method. Results Twenty-three compounds were isolated and their structures were identified as pubinernoid A (1), (2R,6R,9R)-2,9-dihydroxy-4-megastigmen-3-one (2), 3S,5R-dihydroxy-6R,7-megastigmadien-9-one (3), dehydrovomifoliol (4), blumenol A (5), blumenol B (6), oleanolic acid (7), 2α,3α-dihydroxyurs-12-ene-28-oic acid (8), 1α,2α,3β-trihydroxyolean-12-ene-28-oic acid (9), 2α,19α-dihydroxyursolic acid (10), 3α-hydroxyfriedel-2-one (11), 7-oxopetrosterol (12), 7-oxositosterol (13), syringaresinol (14), lariciresinol (15), daphneticin (16), umbelliferone (17), trans-p-hydroxycinnamic acid methyl ester (18), p-hydroxyphenylpropionic acid (19), p-hydrobenzaldehyde (20), p-methoxybenzaldehyde (21), p-methoxybenzoic acid (22), and 5-hydroxymethyl-2-furfural (23). Conclusion Compounds 1-16 and 18-23 are isolated from the genus Viol for the first time, and compound 17 is isolated from the plant for the first time.

Anti-complement alkaloids from whole plants of Viola yedoensis / 中国中药杂志

Fifteen alkaloids were isolated from the 95% ethanol extract of the whole plants of Viola yedoensis by various column chromatographic techniques such as silica gel and Sephadex LH-20. Their structures were identified as neoechinulin A（1）,N-benzoyl-L-p-hydroxy-phenylalaninol（2）,aurantiamide acetate（3）,aurantiamide（4）,anabellamide（5）,trichosanatine（6）,indole-3-carboxylic acid methyl ester（7）,3-carboxyindole（8）,N-trans-feruloyl-tyramine（9）,paprazine（10）,7'-（3', 4'-dihydroxyphenyl）-N-[(4-methoxyphenyl)ethyl]propenamide（11）,cannabisin F（12）,N-(4-hydroxyphenethyl)octacosanamide（13）,N-(4-hydroxyphenethyl)hexacosanamide（14）and N-benzoyl-L-phenylalaninol（15）. All the compounds except 3 and 4 were isolated from this plant for the first time. These alkaloids exhibited anti-complement activity against the classical pathway(CP)and the alternative pathway(AP)with the CH50 and AP50 values ranging from 0.12 to 0.33 g•L⁻¹ and 0.22 to 0.50 g•L⁻¹, respectively. Preliminary mechanism study using complement-depleted sera showed that these alkaloids acted on different complement components in the complement activation cascade.

Impacts of DES on the expressions of related genes in the gubernaculums testis of newborn mice / 中华男科学杂志

Objective@#To investigate the influence of diethylstilbestrol (DES) on the mRNA expressions of the androgen receptor (AR), estrogen receptor α (ERα), proliferating cell nuclear antigen (PCNA), and actin alpha 1 (ACTα1) in the gubernaculums testis of newborn mice and explore their action mechanisms.@*METHODS@#A total of 140 male Kunming mice were randomly divided into a blank control, a dimethyl sulfoxide (DMSO) control, and 5 experimental groups to be treated subcutaneously with normal saline, DMSO, and DES at 0.02, 0.1, 0.5, 10 and 50 μg per kg of the body weight per day, respectively, at gestation days 9－17. On the first day after birth, the animals were sacrificed and the gubernaculums testis collected for detection of the mRNA expressions of AR, ERα, PCNA and ACTα1 by RT-PCR.@*RESULTS@#Compared with the DMSO control, the experimental groups, particularly the DES 10 and 50 μg groups, showed significant increases in the mRNA expression of ERα (RE2 = 0.825, P <0.05), but remarkable decreases in those of AR, PCNA and ACTα1 (RA2 = 0.713, RP2 = 0.946, RT2 = 0.960, P <0.01), all in a dose-dependent manner.@*CONCLUSIONS@#The AR, ERα, PCNA, and ACTα1 mRNA are expressed in the gubernaculum testis of normal newborn mice, and their expression levels may be influenced by intervention with different concentrations of DES during the gestation. Exogenous estrogens may affect the proliferation and contraction of gubernaculum testis cells and consequently the normal development of the testis or even the whole male reproductive system by influencing the metabolism of ER and/or AR.

Evaluation of liver reserve function with Gd-EOB-DTPA enhanced MRI in patients with hepatitis B cirrhosis / 实用放射学杂志

Objective To evaluate the ability of Gd-EOB-DTPA enhanced MRI in the evaluation of liver reserve function in patients with hepatitis B cirrhosis.Methods Patients with hepatitis B cirrhosis and controls with normal liver function and free of chronic liver disease were collected prospectively.Signal intensity(SI)of each hepatic segments(S1-S8)were measured of all cases before injection and after bolus administration of Gd-EOB-DTPA,and the whole liver signal intensity was assessed as the average signal intensity.The whole liver relative enhancement degree(relative enhancement RE)was calculated.The one way A NOVA was used to compare SI and RE among four groups at different time and the Friedman test was used to compare SI and RE within each group at different time.The Spearman rank correlation analysis was used to do correlation analysis.ROC curve was used to analyze the efficacy of Gd-EOB-DTPA enhanced MRI in the diagnosis of liver dysfunction and was used to compare the diagnostic performance of SI and RE in discriminating normal liver function group-Child A from Child B-C.Results Patients enrolled with normal liver function,Child-Pugh A,B and C was 21, 40,48 and 11.SI and RE between different groups were statistically significant at each time(P<0.05);and was statistically significant at different time within the same group.Correlation analysis of SI and RE with liver function classification at different time points showed:in addition to SI20 s(r= -0.190,P= 0.038),RE20 s(r=0.081,P=0.382),SI and RE at each time point were highly negatively related with liver function classification(P<0.01).SI10 minand RE10 minwere higher significantly negatively related with liver function classification.T he area under the ROC curve was 0.839,0.707,0.779 and 0.547,respectively.Conclusion Gd-EOB-DTPA enhanced MRI can assess liver reserve function in patients with hepatitis B cirrhosis,SI and RE can reflect the degree of liver function reserve in a certain extent.It has some value in predicting the normal or mild injury of liver function with moderate or severe injury of liver function.

Determination of six alkaloids in six types of Coptidis Rhizoma pieces by RP-HPLC and spectrum-effect relationships with anti-diabetes pharmacodynamics data / 中国中药杂志

To establish a method for determining the contents of six alkaloids (jatrorrhizine hydrochloride, columbamine hydrochloride, epiberberine hydrochloride, coptisine hydrochloride, palmatine hydrochloride, berberine hydrochloride) in six types of Coptidis Rhizoma pieces (crude pieces, ginger juice stir-fried pieces, vinegar stir-fried pieces, wine steamed pieces, wine stir-fried pieces, evodiae juice stir-fried pieces) by RP-HPLC, and explore the relationship with the curative effect of traditional Chinese medicine (TCM) and pharmacodynamics results. The chromatographic column was Welch XtimateTM C₁₈ (4.6 mm×250 mm, 5 μm), with 0.1% triethylamine solution (adjust pH at 10 with ammonium bicarbonate and ammonia) as mobile phase A and acetonitrile as mobile phase B for gradient elution (0-15 min, 10%-25%B; 15-25 min, 25%-30%B; 25-40 min, 30%-45%B) at a rate of 1.0 mL•min⁻¹. The column temperature was set at 30 ℃, and the wavelength was set at 270 nm. The six alkaloids showed a good linear relationship within the range of 0.85-16.96 mg•L⁻¹ (r=0.999 7), 1.25-24.96 mg•L⁻¹ (r=0.999 9), 2.05-40.96 mg•L⁻¹ (r=0.999 9), 3.65-72.96 mg•L⁻¹ (r=0.999 9), 2.88-57.60 mg•L⁻¹ (r=0.999 8), and 13.25-264.96 mg•L⁻¹ (r=0.999 6) respectively. The average recoveries (n=9) of the six alkaloids were 102.4% (RSD 1.2%), 101.8% (RSD 1.3%), 100.3% (RSD 1.8%), 100.7%(RSD 1.8%), 101.2% (RSD 1.5%) and 97.90% (RSD 2.0%) respectively, and their average contents were 3.55, 4.49, 9.12, 19.17, 15.69, 62.56 mg•g⁻¹, respectively. This determination method was accurate and repeatable, which could be used for the content determination in six types of Coptidis Rhizoma pieces. Data analysis on contents determination and preliminary pharmacodynamics results was conducted by using principal component analysis (PCA) and hierarchical clustering analysis (HCA). The analysis results showed that three types of Coptidis Rhizoma pieces (wine steamed pieces, wine stir-fried pieces, and evodiae juice stir-fried pieces) had significant differences with crude pieces, and the wine steamed Coptidis Rhizoma pieces showed most difference with crude pieces especially, mainly related to triglyceride (TG) and fasting blood glucose levels (FBG) in serum. In addition, columbamine hydrochloride was most affected among the six alkaloids. Those three types of Coptidis Rhizoma pieces (wine steamed pieces, wine stir-fried pieces, and evodiae juice stir-fried pieces), had more advantages for "anti-diabetes" in TCM clinical application, especially in the treatment of diabetic hyperlipidemia.

High-quality Health Information Provision for Stroke Patients / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>High-quality information provision can allow stroke patients to effectively participate in healthcare decision-making, better manage the stroke, and make a good recovery. In this study, we reviewed information needs of stroke patients, methods for providing information to patients, and considerations needed by the information providers.</p><p><b>DATA SOURCES</b>The literature concerning or including information provision for patients with stroke in English was collected from PubMed published from 1990 to 2015.</p><p><b>STUDY SELECTION</b>We included all the relevant articles on information provision for stroke patients in English, with no limitation of study design.</p><p><b>RESULTS</b>Stroke is a major public health concern worldwide. High-quality and effective health information provision plays an essential role in helping patients to actively take part in decision-making and healthcare, and empowering them to effectively self-manage their long-standing chronic conditions. Different methods for providing information to patients have their relative merits and suitability, and as a result, the effective strategies taken by health professionals may include providing high-quality information, meeting patients' individual needs, using suitable methods in providing information, and maintaining active involvement of patients.</p><p><b>CONCLUSIONS</b>It is suggested that to enable stroke patients to access high-quality health information, greater efforts need to be made to ensure patients to receive accurate and current evidence-based information which meets their individual needs. Health professionals should use suitable information delivery methods, and actively involve stroke patients in information provision.</p>

Individualized Immunosuppressive Protocol of Liver Transplant Recipient Should be Made Based on Splenic Function Status / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lymphocyte subsets play important roles in rejection in liver transplant recipients, and the effect of splenic function on these roles remains unknown. The aim of this study was to explore the feasibility to adjust immunosuppressive agents based on splenic function status through detecting the lymphocyte subsets in liver transplantBeijing recipients.</p><p><b>METHODS</b>The lymphocyte subsets of 49 liver transplant recipients were assessed in the 309th Hospital of Chinese People's Liberation Army between June 2014 and August 2015. The patients were divided into splenectomy group (n = 9), normal splenic function group (n = 24), and hypersplenism group (n = 16). The percentages and counts of CD4+ T, CD8+ T, natural killer (NK) cell, B-cell, regulatory B-cell (Breg), and regulatory T-cell (Treg) were detected by flow cytometer. In addition, the immunosuppressive agents, histories of rejection and infection, and postoperative time of the patients were compared among the three groups.</p><p><b>RESULTS</b>There was no significant difference of clinical characteristics among the three groups. The percentage of CD19+CD24+CD38+ Breg was significantly higher in hypersplenism group than normal splenic function group and splenectomy group (3.29 ± 0.97% vs. 2.12 ± 1.08% and 1.90 ± 0.99%, P = 0.001). The same result was found in CD4+CD25+FoxP3+ Treg percentage (0.97 ± 0.39% vs. 0.54 ± 0.31% and 0.56 ± 0.28%, P = 0.001). The counts of CD8+ T-cell, CD4+ T-cell, and NK cell were significantly lower in hypersplenism group than normal splenic function group (254.25 ± 149.08 vs. 476.96 ± 225.52, P= 0.002; 301.69 ± 154.39 vs. 532.50 ± 194.42, P= 0.000; and 88.56 ± 63.15 vs. 188.33 ± 134.51, P = 0.048). Moreover, the counts of CD4+ T-cell and NK cell were significantly lower in hypersplenism group than splenectomy group (301.69 ± 154.39 vs. 491.89 ± 132.31, P= 0.033; and 88.56 ± 63.15 vs. 226.00 ± 168.85, P = 0.032).</p><p><b>CONCLUSION</b>Splenic function status might affect the immunity of liver transplant recipients, that should be considered when we make immunosuppressive protocols.</p>

Effect of arctiin on mouse podocyte epithelial-mesenchymal transition induced by advanced oxidation protein products / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of arctiin on mouse podocyte epithelial-mesenchymal transition (EMT) induced by advanced oxidation protein products (AOPP).</p><p><b>METHODS</b>Mouse podocytes were stimulated by 200 µg/ml AOPP for 24 h in the presence of 50, 100, 200, and 400 µmol/L arctiin. The expressions of α-smooth muscle actin, Grp78 and CHOP were detected using Western blotting.</p><p><b>RESULT</b>The expressions of α-SMA, Grp78 and CHOP were inhibited by arctiin, showing a dose-dependent effect within a given range of arctiin concentration.</p><p><b>CONCLUSION</b>AOPP causes endoplasmic reticulum stress to induce EMT of mouse podocytes, and arctiin can decrease EMT by alleviating the stress. This finding sheds light on a new scope of research of renal fibrosis.</p>

Connective tissue growth factor mediates high glucose-induced down-regulation of podocalyxin expression in mouse podocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the effect of connective tissue growth factor (CTGF) on podocalyxin expression in mouse podocytes exposed to high glucose in vitro and explore the possible pathway involved.</p><p><b>METHODS</b>The expression vector carrying a small interfering RNA (siRNA) targeting CTGF was transfected into mouse podocytes cultured in the presence of 1 g/L glucose (normal control), 4.5 g/L glucose (high glucose group), 1 g/L glucose + 3.5 g/L mannitol (iso-osmolar control group). The changes in the protein expression levels of podocalyxin, CTGF and ERK1/2 in the cells in response to the treatments were investigated using Western blotting.</p><p><b>RESULTS</b>High glucose exposure for 24 and 48 h resulted in significantly decreased expression of podocalyxin and increased CTGF in the podocytes (P<0.05). Phosphorylation of ERK1/2 occurred as early as 30 min after the exposure, and the activation was maintained till 24 h. Transfection of the cells with siRNA targeting CTGF significantly inhibited these changes.</p><p><b>CONCLUSION</b>CTGF is an important mediator of high glucose-induced podocyte damage and decreases the protein level of podocalyxin by the ERK1/2 pathway. CTGF-specific siRNA can alleviate high glucose-induced podocyte injury, suggesting its potential value in treatment of diabetic nephropathy.</p>

Impact of ultrasound-mediated microbubbles on myocardial vascular permeability in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the impact of high-dose microbubbles induced by high mechanical index myocardial contrast echocardiography (MCE) on vascular permeability and its recovery time in rats.</p><p><b>METHODS</b>Thirty male Wistar rats were randomized into 4 MCE groups (groups A-D) and a control group. In the MCE groups, Evans blue was injected at 10 s before MCE (A), immediately after the end of MCE (B), and at 5 min (C) and 20 min after the end of MCE (D). In the control group, the microbubbles and Evans blue were injected at the end of a 5-min ultrasound exposure. All the rats were sacrificed 5 min after Evans blue injection, and the content of Evans blue in the myocardium and the percentage of Evans blue leakage area were determined.</p><p><b>RESULTS</b>The percentage of Evans blue leakage area in groups A, B and C were significantly higher than that in the control group (P<0.05), while the percentage was similar between group D and the control group (P>0.05). Evans blue contents in groups A and B were significantly higher than that in the control group (P<0.05), but groups C and D showed comparable contents with the control group E (P>0.05). No significant changes of the heart rates and premature beat number were observed during and after MCE in these groups (P>0.05).</p><p><b>CONCLUSION</b>High mechanical index MCE and a high contrast dose may induce increased microvascular leakage in rats, and the vascular permeability can recover in 20 min after MCE.</p>

Effects of polyethylene oxide at different concentrations on abdominal aortic blood flow and vascular resistance in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of polyethylene oxide (PEO) solution at different concentrations on abdominal aortic blood flow and vascular resistance in rats and evaluate the safety and drag-reducing effect of PEO solution.</p><p><b>METHODS</b>Thirty-two rats were anesthetized and randomly divided into 4 groups. An ultrasonic flow probe was deployed on the abdominal aorta (5 mm above the common iliac artery) to measure the blood flow. The carotid artery pressure, iliac artery pressure, iliac vein pressure, central venous pressure (CVP) and ECG were also monitored. Saline or different concentrations of PEO [(1x10(-6)(low), 1x10(-5)(middle) and 5x10(-5)(high) g/ml)] were injected in the 4 groups of rats through the caudal vein at a constant rate of 5 ml/h for 20 min, and the changes of the vascular resistance was observed. RESULTS After injections of 1x10(-6) and 1x10(-5) g/ml PEO, the abdominal aortic flow increased significantly (P<0.05) while the vascular resistance was reduced (P(low)=0.052, P(middle)<0.001) as compared to those in the saline control group. Following the injection with 5x10(-5) g/ml PEO, the abdominal aortic flow increased to a threshold in the initial 4 min, after which it rapidly decreased to approach the baseline levels despite continuous infusion. Blood pressure remained stable after the injections except for 5x10(-5) g/mlPEO injection, which resulted in a reduction of the blood pressure by about 10 mmHg (P=0.014). The heart rate and CVP both underwent no significant changes following the injections.</p><p><b>CONCLUSION</b>The drag-reducing effect of PEO is closely related to its concentration, and compared with 1x10(-6) g/ml, 1x10(-5) g/ml PEO more effectively increases the blood flow and decreases the resistance. The effectiveness and safety of EPO are attenuated at a concentration higher than 5x10(-5) g/ml.</p>

Effect of polyethylene oxide on red blood cell velocity in rat cremaster microcirculation / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the drag-reducing effect of polyethylene oxide (PEO) on the velocity of red blood cells in rat cremaster microcirculation.</p><p><b>METHODS</b>Blood samples were collected from 6 Wistar male rats (100-110 g) via the post-orbital venous plexus. The red blood cells were separated by centrifugation and labeled by fluorescinisothiocyate (FITC). After successful establishment of cremaster model, the labeled red blood cells were injected into the jugular vein, and the microcirculation was observed and recorded under fluorescence microscope. The hemodynamic parameters and microcirculation video was recorded every 4 min since 4 min before PEO or normal saline injection. Both PEO (10 ppm) and normal saline was injected into the same rat in random sequence at a constant rate of 3.5 ml/h for 20 min followed by observation for another 20 min. The velocity of the labeled-red blood cells was determined by IPP 6.0 software.</p><p><b>RESULTS</b>Compared with normal saline, PEO significantly increased the velocity of the red blood cells in the rat cremaster microcirculation (498.7-/+182.89 microm/s vs 773.54-/+308.27 microm/s, P=0.012). No significant changes in the heart rate and arterial blood pressure were observed during the experiment (P=0.836, P=0.420).</p><p><b>CONCLUSION</b>PEO at an extremely low concentration can significantly increase the velocity of the red blood cells in rat cremaster microcirculation and produces no significant impact on heart rate and arterial blood pressure.</p>

Effects of small interfering RNA targeting connective tissue growth factor on high glucose-induced human tubular epithelial hypertrophy / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of transfection with small interfering RNA (siRNA) targeting connective tissue growth factor (CTGF) on human tubular epithelial hypertrophy induced by high glucose.</p><p><b>METHODS</b>HK-2 cells were cultured in DMEM/F12 medium containing 1 g/L glucose (normal control group), 4.5 g/L glucose (high glucose group), or 1 g/L glucose+3.5 g/L mannitol (iso-osmolar control group). The cells were transfected with pGenesil-1, pGenesil/neg, or pGenesil/siRNA-CTGF and then cultured in DMEM/F12 medium containing 4.5 g/L glucose as the high glucose+blank control group, high glucose+negative control group and high glucose+interference group, respectively. After cell culture for 24, 48 and 96 h, the cells were collected to detect the mRNA and protein levels of CTGF by real-time PCR and Western blotting, respectively. The proliferative activities of the cells were evaluated with MTT assay, and the total cellular protein contents were determined with Bradford method. Flow cytometry was employed to analyzed the cell cycle changes.</p><p><b>RESULTS</b>High-glucose significantly up-regulated the CTGF mRNA and protein levels in HK-2 cells. The cell proliferation was inhibited after high-glucose exposure with increased cell percentage in G1 phase and total cellular protein content suggesting cellular hypertrophy. Transfection with siRNA targeting CTGF significantly inhibited high glucose-induced up-regulation of CTGF mRNA and protein and promoted the cell proliferation, resulting also increased cells in S phase and lowered total cellular protein contents.</p><p><b>CONCLUSION</b>CTGF is an important mediator of high glucose-induced tubular epithelial hypertrophy, and transfection with siRNA targeting CTGF can alleviate the hypertrophy, suggesting the potential value of CTGF-targeted treatment in the management of diabetic nephropathy.</p>

Immune regulation effect of rat dendritic cells phagocytosing photochemotherapy-treated allogeneic cells on syngeneic T cells / 中国实验血液学杂志

The aim of this study was to investigate the immune regulatory effect of dendritic cells phagocytosing photochemotherapy-treated allogeneic spleen lymphocytes on syngeneic T cells. DA rat spleen lymphocytes were treated with 8-methoxypsoralen plus UVA irradiation (PUVA). LEW rat bone marrow-derived DCs were co-cultured with PUVA-treated DA spleen lymphocytes (PUVA-SP), and the surface markers (MHC-II, CD86 and CD40) of treated DC were detected by flow cytometry. CFSE-labeled PUVA SP were incubated with LEW DCs and the phagocytosis of DCs on PUVA-SP was observed by using fluorescent microscope. The ability of DC phagocytosing allogeneic PUVA-SP (PUVA-SP DC) to stimulate the proliferation of LEW T cells was analyzed by mixed leukocyte reactions (MLR). The production of IL-4, IL-10, IL-2, IFN-gamma in MLR culture supernatant was determined by luminex method. The results indicated that the PUVA treatment effectively induced early apoptosis of DA rat spleen lymphocytes. After co-culture, DC efficiently phagocytosed allogeneic PUVA-SP and still maintained an immature phenotype with low levels of MHC II, CD40 and CD86. PUVA-SP DC induced LEW T cell hyporesponsiveness to DA rat antigen, and led to skewing of T cell cytokine expression toward Th2 (IL-10 and IL-4). It is concluded that the PUVA-SP DC effectively down-regulate T cell response to alloantigen and induce Th2 immune deviation in vitro.

Evaluation of left ventricular diastolic function in canine acute myocardial ischemia using velocity vector imaging and quantitative tissue velocity imaging / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of velocity vector imaging (VVI) and quantitative tissue velocity imaging (QTVI) in assessing left ventricular diastolic function of the dogs with acute myocardial ischemia.</p><p><b>METHODS</b>Six healthy mongrel dogs were subjected to ligation of the left circumflex artery or left anterior descending artery to induce coronary artery stenosis of varying degrees. The mean peak diastolic velocity (Em) of the ventricular walls around the mitral annulus was recorded with VVI or QTVI in the coronary blood flow. The left ventricular end diastolic pressure (LVEDP) was measured with pigtail catheter in the left ventricle.</p><p><b>RESULTS</b>As the coronary blood flow decreased, LVEDP was gradually increased, and Em measured by VVI or QTVI were also gradually decreased. A good linear correlation was shown between Em measured by VVI or QTVI and LVEDP (r=-0.834, P<0.001, and r=-0.68, P<0.001, respectively). A significant difference was observed in the correlation coefficient between VVI and QTVI (Z=2.625, P=0.0087).</p><p><b>CONCLUSION</b>VVI and QTVI both provide good noninvasive means for measuring left ventricular diastolic function. VVI, a new echocardiographic modality without angular dependence, is better than QTVI in evaluating left ventricular diastolic function.</p>

Studies on chemical constituents from root of Hedysarum polybotrys / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of Hedysarum polybotrys.</p><p><b>METHOD</b>Chromatographic methods were used to isolate compounds from H. polybotrys and chemical and spectral methods were used to elucidate the structures of the isolated compounds.</p><p><b>RESULT</b>Five compounds, N,N,N-trimethyl-tropaphone inner salt (hypaphorine) (1), octadecyl-3-methoxy-4-hydroxy-benzeneacrylate (2), 5,7,4'-trihydroxy-dihydroflavanone 5,7-di-O-beta-D-glucopyranoside (3), 3,4,5-trimethoxy cinnamic acid methy ester (4) and vanillic acid (5), were isolated from the roots of H. polybotrys.</p><p><b>CONCLUSION</b>Compounds 1, 2 and 3 were obtained from this plant for the first time, while compounds 1 and 2 were isolated from Hedysarum for the first time.</p>

Studies on chemical constituents of Hedysarum polybotrys / 药学学报

<p><b>AIM</b>To study the chemical constituents of Hedysarum polybotrys Hand.-Mazz..</p><p><b>METHODS</b>The compounds were separated with Sephadex LH-20 and silica gel column chromatography, and their structures were identified on the basis of spectral analysis.</p><p><b>RESULTS</b>Five compounds were identified as hedysalignan A (1), isoliquiritigenin (2), formononetin (3), calycosin (4) and ononin (5).</p><p><b>CONCLUSION</b>Hedysalignan (1) is a new compound and the others were obtained from the plant for the first time.</p>