Design, synthesis and study of anti-tumor activity of thiazolinone urea derivatives bearing aryloxypyridinone fragments / 药学学报

Taking cabozantinib as leading compound, 13 novel small molecular c-Met inhibitors were designed and synthesized based on the obtained structure-activity relationships (SARs) of c-Met inhibitors. The structures of compounds were confirmed by 1H NMR, 13C NMR and HR-MS. In vitro anti-tumor activity was evaluated by MTT method, and the mechanism was preliminarily disclosed by real-time dynamic living cell imaging and flow cytometry analysis. The results indicated that most of compounds showed good inhibition activity against human non-small-cell carcinoma cell A549 and human colorectal cancer cell HT-29 which was superior to cabozantinb. Compounds showed excellent cytotoxity and anti-proliferative activity against HT-29, and promoted cell apoptosis.

Intravascular Ultrasound Classification of Plaque in Angiographic True Bifurcation Lesions of the Left Main Coronary Artery / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Accurately, characterizing plaques is critical for selecting the optimal intervention strategy for the left main coronary artery (LMCA) bifurcation. Coronary angiography cannot precisely assess the location or nature of plaques in bifurcation lesions. Few intravascular ultrasound (IVUS) classification scheme has been reported for angiographic imaging of true bifurcation lesions of the unprotected LMCA thus far. In addition, the plaque composition at the bifurcation has not been elucidated. This study aimed to detect plaque composition at LMCA bifurcation lesions by IVUS.</p><p><b>METHODS</b>Fifty-eight patients were recruited. The location, concentricity or eccentricity, site of maximum thickness, and composition of plaques of the distal LMCA, ostial left anterior descending (LAD) coronary artery and, left circumflex (LCX) coronary artery were assessed using IVUS and described using illustrative diagrams.</p><p><b>RESULTS</b>True bifurcation lesions of the unprotected LMCA were classified into four types: Type A, with continuous involvement from the distal LMCA to the ostial LAD and the ostial LCX with eccentric plaques; Type B, with concentric plaques at the distal LMCA, eccentric plaques at the ostial LAD, and no plaques at the LCX; Type C, with continuous involvement from the distal LMCA to the ostial LCX, with eccentric plaques, and to the ostial LAD, with eccentric plaques; and Type D, with continuous involvement from the distal LMCA to the ostial LAD, with eccentric plaques, and to the ostial LCX, with concentric plaques. The carina was involved in only 3.5% of the plaques. A total of 51.7% of the plaques at the ostium of the LAD were soft, while 44.8% and 44.6% were fibrous in the distal LMCA and in the ostial LCX, respectively.</p><p><b>CONCLUSIONS</b>We classified LMCA true bifurcation lesions into four types. The carina was always free from disease. Plaques at the ostial LAD tended to be soft, whereas those at the ostial LCX and the distal LMCA tended to be fibrous.</p>

Abnormal function of the posterior cingulate cortex in heroin addicted users during resting-state and drug-cue stimulation task / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous animal and neuroimaging studies have demonstrated that brain function in heroin addicted users is impaired. However, the posterior cingulate cortex (PCC) has not received much attention. The purpose of this study was to investigate whether chronic heroin use is associated with craving-related changes in the functional connectivity of the PCC of heroin addicted users.</p><p><b>METHODS</b>Fourteen male adult chronic heroin users and fifteen age and gender-matched healthy subjects participated in the present study. The participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and a cue-induced craving task fMRI scan. The activated PCC was identified in the cue-induced craving task by means of a group contrast test. Functional connectivity was analyzed based on resting-state fMRI data in order to determine the correlation between brain regions. The relationship between the connectivity of specific regions and heroin dependence was investigated.</p><p><b>RESULTS</b>The activation of PCC, bilateral anterior cingulate cortex, caudate, putamen, precuneus, and thalamus was significant in the heroin group compared to the healthy group in the cue-induced craving task. The detectable functional connectivity of the heroin users was stronger between the PCC and bilateral insula, bilateral dorsal striatum, right inferior parietal lobule (IPL) and right supramarginal gyrus (P < 0.001) compared to that of the healthy subjects in the resting-state data analysis. The strength of the functional connectivity, both for the PCC-insula (r = 0.60, P < 0.05) and for PCC-striatum (r = 0.58, P < 0.05), was positively correlated with the duration of heroin use.</p><p><b>CONCLUSION</b>The altered functional connectivity patterns in the PCC-insula and PCC-striatum areas may be regarded as biomarkers of brain damage severity in chronic heroin users.</p>

The influence of zi-hua burn cream on the survival of random skin flaps in rats / 中华整形外科杂志

<p><b>OBJECTIVE</b>To observe the effect of zi-hua burn cream on the survival of skin flaps in rats, and its mechanisms.</p><p><b>METHODS</b>72 Wistar rats, were randomly divided into four groups as zi-hua group(n = 18, external application of alfalfa burn cream), control group (n = 18, external application of heparin sodium cream), model group (n = 18, external application of vaseline) , negative control (n = 18, no operation). 8 cm x 2 cm random skin flaps with pedicle on the side of head were designed on the back of Wistar rats. The drug was applied on the flap surface, 2 times a day. The survival of skin flaps was observed. The change of serum superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), turner necrosis factor-alpha(TNF-alpha)and interleukin-6(IL-6)were compared at 1,2,3,7 d after operation, and histologic examination was performed.</p><p><b>RESULTS</b>The survival rate of zi-hua group (73.58 - 10. 74)% was significantly higher than that of model group (33.40 - 16.05) %, showing a statistical difference (Q = 10.63, P <0.01). There was no significant difference between the zi-hua group and control group (71.65 +/- 11. 92) %. The level of serum SOD, NO in zi-hua group and control group was higher than that in model group, while the level of serum MDA, TNF-alpha and IL-6 was lower than that in model group(P <0.01). On 7 day after operation, skin flaps tissue edema,necrosis and inflammatory cell infiltration in zi-hua group and control group was less obvious than that in model group. There was significant proliferation of granuloma and fibroblast and formation of neonatal capillary in zi-hua group and control group. The vascular density in zi-hua group was obviously higher than that in the model group and control group(P <0. 01).</p><p><b>CONCLUSIONS</b>Zi-hua burn cream could significantly improve the blood supply of skin flaps, increase the survival rate of skin flaps in rats. Its mechanism may be associated with the anti-free-radical-damage action, improve local microcirculation, improve the NO content, reduce the TNF-alpha and IL-6 level, reduce inflammation factor release, improve oxidative stress state, and reduce inflammation reaction.</p>

Changes in functional connectivity of ventral anterior cingulate cortex in heroin abusers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies with animal experiments, autopsy, structural magnetic resonance imaging (MRI) and task-related functional MRI (fMRI) have confirmed that brain functional connectivity in addicts has become impaired. The goal of this study was to investigate the alteration of resting-state functional connectivity of the ventral anterior cingulate cortex (vACC) in the heroin abusers' brain.</p><p><b>METHODS</b>Fifteen heroin abusers and fifteen matched healthy volunteers were studied using vACC as the region-of interest (ROI) seed. A 3.0 T scanner with a standard head coil was the imagining apparatus. T2*-weighted gradient-echo planar imaging (GRE-EPI) was the scanning protocol. A ROI seed based correlation analysis used a SPM5 software package as the tool for all images processing.</p><p><b>RESULTS</b>This study showed a functional connection to the insula vACC in heroin abusers. Compared with controls, heroin users showed decreased functional connectivity between the nucleus accumbens (NAc) and vACC, between the parahippocampala gyrus/amgdala (PHC/amygdala) and vACC, between the thalamus and vACC, and between the posterior cingulated cortex/precuneus (PCC/pC) and vACC.</p><p><b>CONCLUSION</b>The altered resting-state functional connectivity to the vACC suggests the neural circuitry on which the addictive drug has an affect and reflects the dysfunction of the addictive brain.</p>

A free-breathing non-contrast-enhanced pulmonary magnetic resonance angiography at 3 Tesla / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The breathhold contrast-enhanced three-dimensional magnetic resonance angiography (MRA) using T1-weighted gradient-echo imaging sequence is the standard technique for MRA of the thorax. However, this technique is not desirable for certain patients with respiratory insufficiency, serious renal impairment, or allergy to contrast agents. The objective of this study was to optimize and evaluate a non-contrast-enhanced free-breathing pulmonary MRA protocol at 3 Tesla.</p><p><b>METHODS</b>The time-of-flight protocol was based on a two-dimensional T1-weighted turbo field echo sequence with slice-selective inversion recovery and magnetization transfer preparation together with respiratory navigator gating, cardiac gating, and parallel imaging. Optimal values for time of inversion delay, flip angle and slice thickness were experimentally determined and used for all subjects.</p><p><b>RESULTS</b>Excellent pulmonary MRA images, in which the 7th order branches of pulmonary arteries could be reliably identified, were obtained in the 12 free-breathing healthy volunteers. TI of approximately 300 ms provides the best suppression of background thoracic and cardiac muscles and effective inflow enhancement. With increasing flip angle, the pulmonary vessels gradually brightened and exhibited optimal contrast at 20 degrees-30 degrees. The 2 mm slice thickness and 0.5 mm slice overlap is suitable for visualization of the peripheral pulmonary vessel.</p><p><b>CONCLUSIONS</b>The MRA protocol at 3 Tesla may have clinical significance for pulmonary vascular imaging in patients who are not available for contrast-enhanced 3D MRA and CT angiography examination or are unable to sustain a long breath-hold.</p>

Astragalus protects the testis following testicular torsion/detorsion in rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of astragalus on testis tissues following unilateral testicular torsion/detorsion.</p><p><b>METHODS</b>Thirty healthy adult Wistar rats were equally randomized into Group A (sham-operation control), B (torsion/detorsion) and C (torsion/detorsion plus intraperitoneal injection of astragalus). The testicular torsion/detorsion model was established by the Turner method. All the rats were fed under the same condition for 7 days and sacrificed, and the torsional testes were harvested for the detection of germ cell apoptosis, glutathione activity and the level of malonic diethylaldehyde (MDA).</p><p><b>RESULTS</b>The apoptosis indexes (AI) of spermatogenic cells in the torsional testes were (5.82 +/- 1.21), (36.18 +/- 8.40) and (20.39 +/- 3.57) in Group A, B and C, significantly higher in Group B and C than in A (P < 0.05) and in Group B than in C (P < 0.05). Significant differences were observed in glutathione activity in the ipsilateral testes among Group A (48.03 +/- 2.01), B (30.93 +/- 1.25), C (38.44 +/- 1.06) U/mg (P< 0.05), as well as in the level of MDA, (1.43 +/- 0.17), (3.98 +/- 0.36), (2.57 +/- 0.53) nmol/ml, among the three groups (P < 0.05).</p><p><b>CONCLUSION</b>Astragalus could significantly reduce the apoptosis of spermatogenic cells, decrease the level of lipid peroxidation and protect glutathione activity in the torsional testis.</p>