Effect of Fei-Liu-Ping ointment combined with cyclophosphamide on lung cancer cell proliferation and acidic microenvironment / 北京大学学报(医学版)

OBJECTIVE@#To observe the effects of Fei-Liu-Ping ointment and chemotherapy on mice with lung cancer, and to explore the inherent mechanism of action from the point of acidic microenvironment and apoptosis.@*METHODS@#First of all, the Lewis lung cancer transplanted mouse model was established. Therefore, they were treated by Fei-Liu-Ping ointment, cyclophosphamide, Fei-Liu-Ping ointment + cyclophosphamide and the saline as control. All the groups' tumor size, tumor growth rate and food consumption were recorded. The mice were sacrificed and the tumors were took out after 15 days' interventions. Then lactate relative concentrations were detected with lactate kits and the protein expressions of glucose transporter 4 (GLUT4), hexokinase 1 (HK1), glucose-regulated protein 78 (GRP78), carbonic anhydrase-IX (CA-IX) were detected through immunohistochemical staining. Flow cytometry was adopted to detect the percentage of apoptotic tumor cells and regulatory T cells (Treg), and the expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2, Bax, Caspase-3, interleukin-2 (IL-2) were tested through western blot.@*RESULTS@#The strongest inhibition effect and the lowest tumor growth rate was found in Fei-Liu-Ping ointment + cyclophosphamide group. There were significant differences between Fei-Liu-Ping ointment + cyclophosphamide group and saline group(P<0.05). And the highest food consumption was found in Fei-Liu-Ping ointment + cyclophosphamide group while there were no significant differences between Fei-Liu-Ping ointment + cyclophosphamide group and saline group (P>0.05). Further molecular biological detections found that the lowest lactate level and regulatory T cells ratio were found in Fei-Liu-Ping ointment + cyclophosphamide group and these expressions of GLUT4, HK1, GRP78, CA-IX were suppressed. There were significant differences between Fei-Liu-Ping ointment+cyclophosphamide group and saline group (P<0.05). In addition, the Fei-Liu-Ping ointment + cyclophosphamide group's cell apoptosis increased significantly compared with saline group and there were significant differences on expressions of HIF-1α, Bcl-2, Bax, Caspase-3, IL-2 for this group compared with saline group.@*CONCLUSION@#Chemotherapy and Fei-Liu-Ping ointment had the synergistic effect on inhibiting tumor growth and improving the general conditions of tumor-bearing mice. The effect was partly owed to the improvement on tissue hypoxia, the inhibition of HIF-1α expression and the regulations on its downstream proteins, such as GLUT4, HK1, GRP78, and CA-IX. And then all these alterations led to the modulation tumor acidic microenvironment, the induced tumor cells apoptosis and suppression of T cells to regulatory T cells differentiation.

Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs / 中国天然药物

Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg).

Preliminary study for the roles and mechanisms of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles in the Lewis lung cancer mice / 北京大学学报(医学版)

Objective:To comparatively observe the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the Lewis lung cancer mice and to explore the mechanisms of Rg3 and PEG-PLGA-Rg3 nanoparticle anti-cancer in vivo.Methods:Lewis lung cancer mouse model was established and 60 mice were randomly divided into 5 groups with twelve in each group:PEG-PLGA-Rg3 nanoparticles group (Rg3-N),PEG-PLGA group (PEG),Rg3 group (Rg3 ),normal control group (C),saline control group(NS),and received intragastric administration for 1 4 days.The weights of the mice were measured every 2 days and the weight curves were obtained.At the same time,the color pattern,activity and men-tal status were observed.The mice were sacrificed when the administration was over,and the effects of 20 (R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on tumor weight,and the tumor:weight ratios were analysed.In addition,the tumor microvessel density (MVD)was measured by immunohistochemi-cal staining with anti-CD31 antibody to compare the effects of Rg3 and PEG-PLGA-Rg3 nanoparticles on the tumor angiogenesis in vivo.Furthermore,the levels of such angiogenesis and proliferation factors as MMP-9,HIF-1 α,VEGF,Ki-67 were examined by RT-PCR,Western blot and immunohistochemistry to explore the internal molecular mechanisms of anti-tumor effects in vivo.Results:The trends of variation of the mice weights in NS group and PEG group were rising early but declining later.In contrast,the trends of the other three groups were rising early and became stable later.In comparison with NS group, the mice of Rg3 group and Rg3-N group had better general status:brighter color,more active and better spirit.Compared with NS group,the tumor weight in PEG group,Rg3 group and Rg3-N group showed no significant difference but the tumor:weight ratio and MVD in Rg3 group and Rg3-N group declined signi-ficantly (P <0.01 ).Besides,there was no significant difference between Rg3 group and Rg3-N group. At the same time,the level of VEGF mRNA,the protein expression of MMP-9,HIF-1 α,VEGF in Rg3 group and Rg3-N group decreased compared with NS group.Furthermore,the level of each index above-mentioned in Rg3-N group was lower than that in Rg3 group.The expression of Ki-67 in PEG group,Rg3 group and Rg3-N group showed no significant difference compared with NS group.Conclusion:Rg3 and PEG-PLGA-Rg3 nanoparticle may suppress the expression of VEGF,MMP-9 and HIF-1 αin Lewis lung cancer mice,thereby indirectly contributing to their antitumor effects and alleviating the mice’s general status.In addition,PEG-PLGA nanoparticles embedding can promote Rg3 antitumor effect in vivo.

C-reactive Protein -717A>G and -286C>T>A Gene Polymorphism and Ischemic Stroke / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Inflammation plays a pivotal role in the formation and progression of ischemic stroke. Recently, more and more epidemiological studies have focused on the association between C-reactive protein (CRP) -717A > G and -286C > T > A genetic polymorphisms and ischemic stroke. However, the findings of these researches are not conclusive.</p><p><b>METHODS</b>We performed a meta-analysis to determine whether these two polymorphisms are associated with the risk of ischemic stroke. Eligible studies were identified from the database of PubMed, Medline, Embase, Web of Science, CNKI, Weipu, and Wanfang. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association.</p><p><b>RESULTS</b>Four articles were included in our study, including 1926 cases and 2678 controls for -717A > G polymorphism, 652 cases and 1103 controls for -286C > T > A polymorphism. The results of meta-analysis showed that single nucleotide polymorphism (SNP) -717A > G was not significantly associated with the risk of ischemic stroke (GG vs. AA, OR = 1.12, 95% CI = 0.83-1.50, P = 0.207; GG + GA vs. AA, OR = 1.04, 95% CI = 0.93-1.17, P = 0.533; GG vs. GA + AA, OR = 1.10, 95% CI = 0.82-1.47, P = 0.220). Meta-analysis of SNP - 286C > T > A also demonstrated no statistical evidence of a significant association with the risk of ischemic stroke (AA vs. CC, OR = 0.86, 95% CI = 0.59-1.25, P = 0.348; AA vs. CC, OR = 0.92, 95% CI = 0.80-1.06, P = 0.609; AA vs. CC, OR = 0.89, 95% CI = 0.62-1.30, P = 0.374).</p><p><b>CONCLUSIONS</b>This meta-analysis demonstrated little evidence to support a role of CRP gene -717A > G, -286C > T > A polymorphisms in ischemic stroke predisposition. However, to draw comprehensive and more reliable conclusions, further larger studies are needed to validate the association between CRP gene polymorphisms and ischemic stroke in various ethnic groups.</p>

Nano material occluder of single rivet type used for percutaneous closure of ventricular septal defect:an experimental study in dogs / 介入放射学杂志

Objective To evaluate the feasibility, efficacy and safety of new nano material occluder of single rivet type (left-disk with no-hub) in treating ventricular septal defect (VSD) in order to provide experimental basis for clinical application. Methods A total of 26 healthy adult dogs were selected for this study . Under thoracotomy , VSD model was established through fluoroscopically-guided percutaneous puncturing of the right ventricular free wall. The models were randomly and equally divided into the study group(n=13, using nano material VSD occluder) and the control group(n=13, using double-hub nitinol occluder). Every two dogs from each group were sacrificed each time at one, 2, and 3 months after percutaneous closure of VSD with corresponding occluder, the tissue samples were collected and sent for gross examination as well as for the optical and electronic microscopy study;the blood concentration of nickel ion was also determined. The state of endothelialization after implantation of the new type occluder was evaluated, and the complications such as residual shunt and superficial thrombus formation were recorded. The results were analyzed. Results By open chest operation with small incision and percutaneous puncturing of the right ventricular free wall, VSD model was successfully established in all 26 dogs. The success rate of the implantation of the VSD occluder in the study group was 100%, while it was 91.7% in the control group. One, 2, 3 and 6 months after the implantation, the heart specimens of 25 dogs were removed and gross examination showed that neither occluder displacement nor alloy wire fracture occurred in both groups. No thrombus formation or vegetation attached on the disk surface was observed. One month after the procedure , in the study group the bilateral disk surfaces of the occluder were covered with thin layer transparent tissue , which were proved to be composed of the fibrous tissue and endothelial cells through pathologic and electronic microscopy study. Six months after implantation, the superficial tissue of the occluder became further thickened and the occluder edge became fused with the surrounding heart tissue. Conclusion The design of the new VSD nano materials occluder, which has a left-disk with no hub, is very scientific. Compared with double-hub nitinol occluder, the new device can shorten the time of complete endothelialization and effectively occlude the VSD. Therefore, this new nano material occluder has promising prospect in clinical application.

Comparative study of eyelid closure induced by electric exciting different sites on odoiculads oculi muscle / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>Directly excited the denervated orbicularis oculi muscle (OOM) by electric current on rabbits, to induce efficient eyelid closure, and seek the optimal sites for such excitation that can produce efficient eyelid closure with the minimal excitating current in the least channel.</p><p><b>METHODS</b>Bilateral peripheral facial paralysis model on 20 healthy NewZealand rabbits (40 sides) were prepared. Exciting current was designed for two-way rectangular pulse, 35 Hz frequency and 0.2ms pulse width. The current intensity could be adjusted between 0 and 2.5 mA. Middle of upper-orbit (A), outer orbital rim (B), and middle of lower-orbit (C) sites were located around the OOM. Each site underwent parallel muscle fiber excitation by 2.5 and 5 mm distance dual-electrode respectively, additional dual-electrodes were also placed in A- B and A- C positions. All resulted in a total of 8 different exciting methods, and were labeled A2.5, A5.0, B2.5, B5.0, C2.5, C5.0, AB and AC. Then the current was adjusted to achieve efficient eyelid closure. The minimal current intensity needed was regarded as threshold value.</p><p><b>RESULTS</b>All efficient eyelid closure occurrence rates of 8 methods were compared with combined χ(2) test and showed significant difference. A crossed χ(2) test showed the rates of C2.5, C5.0, and AC was significant lower than the highest methods. Except 3 methods above, the mean threshold values of remain 5 methods were compared with ANOVA test and showed significant difference. Further Fisher's LSD test showed B2.5 had the lowest mean value, was significant lower than A2.5 and AB, P < 0.001, and had no significant difference with A5.0 and B5.0, P > 0.05. A5.0's mean value was significant lower than A2.5's, P < 0.05.</p><p><b>METHODS</b>B2.5, B5.0 and A5.0 were more likely to achieve a perfect closure.</p><p><b>CONCLUSIONS</b>Middle of supraorbital margin (A) and outer orbital rim (B) are the ideal sites for electric excitation. Exciting the two sites can sufficiently induce the contraction of denervated OOM, leading to high efficient eyelid closure occurrence rates, more perfect closure meanwhile with lower threshold current value, which are priority options.</p>

Mechanism of tumor angiogenesis / 国际肿瘤学杂志

Based on the theory of tumor angiogenesis,the vascular system is necessary for the advance and metastasis of the tumor.To inhibit or even cure the tumor,the researchers all over the world have made a great many of studies on the mechanism of tumor angiogenesis and have acquired some achievements.Based on the findings,a lot of factors are involved in tumor angiogenesis,and they constitute the complex regulating network through interaction at the molecular and cellular level.

Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-beta1 expression and fibrosis in minipigs with ischemia-reperfusion injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury.</p><p><b>METHODS</b>Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n = 5) or saline (control group, n = 5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-beta1 was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining.</p><p><b>RESULTS</b>As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 +/- 5.1) to (32.3 +/- 5.6) ml, P < 0.05) and end-systolic volume (from (8.3 +/- 3.2) to (15.2 +/- 4.1) ml, P< 0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 +/- 13.3)% to (50.2 +/- 11.9)%, P < 0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-beta1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P< 0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P < 0.05).</p><p><b>CONCLUSION</b>Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-beta1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.</p>

Diagnosis and surgical treatment of 98 cases with adult primary retroperitoneal malignant tumor / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the diagnosis and surgical treatment of adult primary retroperitoneal malignant tumor (APRMT).</p><p><b>METHODS</b>The clinical data of 98 cases with APRMT underwent resection from January 1990 to April 2003 were analyzed retrospectively.</p><p><b>RESULTS</b>Among the 98 cases, complete excision were performed in 79 cases (80.6%), palliative excision in 16 cases (16.3%), tumor biopsy only in 3 cases (3.1%). Resection of involved adjacent organs were carried out in 25 cases (25.5%) and the re-operation rate for recurrence was 28.6% (28 cases). The 1, 3, 5 year survival rates for 79 cases with complete resection were 93.7%, 73.4% and 34.2%, respectively. The 1, 3, 5 year survival rate for 16 cases with palliative resection were 75.0%, 6.3% and 6.3%, respectively.</p><p><b>CONCLUSIONS</b>Certain imaging examinations are crucial to the diagnosis and preoperative evaluation of APRMT. Resection of the involved organs could improve resection rate and prognosis. For the recurrent cases, earlier reoperation is strongly recommended.</p>

Changes of Pituitary Magnetic Resonance Imaging and Clinical Manifestations in Short Stature Children with Growth Hormone Deficiency / 实用儿科临床杂志

Objective To study the relationship between the clinical manifestations and changes of pituitary magnetic resonance imaging(MRI) in short stature children with growth hormone deficiency(GHD).Methods The pituitary MRI finding in 38 cases of short stature children diagnosed as GHD(males 23,females 15;5-14 years old,10 children were in pubertas and Tanner Ⅱ-Ⅲ) were analyzed,and the pituitary morphology,size,signal and pituitary stalk's shape and location were observed.SPSS 12.0 soffware was used to analyze the data.Results The forms of pituitery were plaque in 20 children(53%),cupped in 17 children(45%),and carinate in 1 children.In the 22 cases of completely GHD,18 cases had different levels of anterior pituitary dysplasia,abnormal pituitary stalk and/or pituitary signal changes,5 cases without posterior lobe disappeared high signal and 4 cases with pituitary stalk interruption syndrome;the other 4 cases had completely normal pituitary.In the 16 cases of partially GHD,7 cases had varying degrees of pituitary size and/or abnormal pituitary stalk,8 cases had completely normal pituitary,and 1 case had pituitary adenoma.Conclusion Pituitary MRI could assist diagnosis and evaluate pituitary function in short stature children.

The predictive value of MR diffusion weighted imaging on the delayed encephalopathy after carbon monoxide poisoning / 中华放射学杂志

Objective To investigate the value of diffusion weighted imaging(DWI)in predicting delayed encephalopathy of the rabbits brain after carbon monoxide(CO)poisoning.Methods Sixty healthy rabbits were put into self-made poisoning cabinet and were poisoned by inhalation of CO.Aeration of CO was stopped when the rabbits became comatous,and the cabinet was kept airpoof for 6 h.The rabbits underwent MRI before poisoning,at 1 h,3 d,5 d,7 d,15 d,30 d,45 d,and 60 d after poisoning respectively. Axial and sagittal T_2WI,axial T_1WI and DWI were performed.In the rabbits that did not show symptoms of delayed encephalopathy,the observation was discontinued on the 60~(th)day.In the rabbit that showed the symptoms,the observation was discontinued on the 30~(th)——45~(th)day.The changing pattern of cortical ADC values before and after CO poisoning was observed and its relationship with delayed encephalopathy was investigated.Results In the group without delayed encephalopathy(15 rabbits),the ADC value at 1 h after poisoning[(7.58?0.36)?10~(-4)mm~2/s]decreased significantly compared with the pre-poisoning value[(8.02?0.35)?10~(-4)mm~2/s](q=0.4441,P0.05).In the group with delayed encephalopathy(15 rabbits),the ADC value at 1 h after poisoning [(7.40?0.32)?10~(-4)mm~2/s]decreased significantly compared with the pre-poisoning value[(8.08? 0.32)?10~(-4)mm~2/s](q=0.6728,P