Objective To explore the mechanism that gold nanorods trigger apoptosis in cancer cells.Methods Gold nanorods was synthesized by gold seed growing method, and its characterization was detected; gold nanorods on cell proliferation-toxicity were evaluated by CCK-8 Kit and apoptosis were detected by flow; mitochondrial membrane potential were tested by JC-1 and activation of Caspase 9 and Caspase 3 were detected by western blot. Results The results found that gold nanorods had nontoxic to normal cells, but highly toxic to tumor cells; and with the increasing of gold nanorods’ working time, the percentage of apoptotic cancer cells was increasing; in addition to, normal cells’ mitochondrial membrane potential did not change, but cancer cells had a significant reduction in mitochondrial membrane potential.Conclusion This study proves that gold nanorods induce apoptosis through the mitochondrial apoptosis pathway.

BACKGROUND: Calcium calmodulin-dependent kinase Ⅱ (CaMKⅡ) can be more active in patients with left ventricular hypertrophy (LVH), which in turn causes phosphorylation of ryanodine receptors, resulting in inactivation and the instability of intracellular calcium homeostasis. The present study aimed to determine the effect of CaMKⅡ–ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia. METHODS: Forty New Zealand rabbits were randomized into four groups (10 per group): sham group, LVH group, KN-93 group (LVH+KN-93), and ryanodine group (LVH+ryanodine). Rabbits in the LVH, KN-93, and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta, while those in the sham group did not undergo the coarctation. After eight weeks, action potentials (APs) were recorded simultaneously in the endocardium and epicardium, and a transmural electrocardiogram (ECG) was also recorded in the rabbit left ventricular wedge model. Drugs were administered to the animals in the KN-93 and ryanodine groups, and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline (1 mol/L) and high-frequency stimulation. RESULTS: The frequency (animals/group) of triggered APs was 0/10 in the sham group, 10/10 in the LVH group, 4/10 in the KN-93 group, and 1/10 in the ryanodine group. The frequencies of ventricular tachycardia were 0/10, 9/10, 3/10, and 1/10, respectively. The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10, 7/10, 2/10, and 1/10, respectively. The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group (P<0.05). CONCLUSIONS: KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH. The CaMKⅡ–ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.

Objective The aim of this study is to observe the effect of combined amiodarone and antiarrhythmic peptide (AAP10) use on the incidence of induced ventricular arrhythmias in healed myocardial infarction (MI) rabbits. Methods Twenty Japanese rabbits underwent thoracotomy without coronary artery ligation( Sham, group A) ,the middle left circumflex branch were ligated to induce MI in 180 Japanese rabbits. Eight weeks after operation, 124 rabbits survived MI operation and were divided into four groups: control group (group B, n =31 ), amiodarone group (group C, n =31 ), AAP10 group (group D,n =31 ) and amiodarone plus AAP10 group ( group E, n =31 ). The A and B and D groups were treated with saline 2 ml/d, the C and E groups were treated with 2 ml saline containing amiodarone 100 mg· kg-1·d-1. All rabbits were examined by echocardiogram at 12 weeks after operation, then anesthetized by sodium barbital, the left wedge ventricular preparations were cannulated and artery perfused by Tyrode's solution in vitro in the absence (Group A, B and C) and presence of AAP10 (500 nmol/L, Group D and E). The volume electrocardiogram, QT Interval, QRS interval, effective refractory period (ERP), the T-peak to Tend interval ( Tp-e ), and ventricular tachycardia episodes induced by programmed stimulation were recorded.The Tp-e/QT ratio was calculated. After perfusion, gap junctions protein connexin 43 (Cx43) expression was detected by Western blot and immunofluorescence. Results The incidence of induced ventricular tachycardia episodes of group A, B, C, D, E was 0, 62. 5%, 26. 9%, 40.0%, 22. 2% respectively. The incidence of induced ventricular tachycardia episodes of group E was less than group B. The Tp-e/QT ratio in group B, C, D were greater than in group A. The Tp-e/QT ratio of group E was less than group B. The myocardial Cx43 in the group B was down-regulated and disorganized compared to group A, up-regulated in group C and E compared to group B, up-regulated in group E compared to group D. The Cx43 in the heart of group D and E were well organized than in group B and C. Conclusions The artery perfused rabbits wedge preparations with healed myocardial infarction with high incidence of induced ventricular tachycardia episodes are good platform for ventricular arrhythmias research. Combined amiodarone and AAP10 use could decrease the Tp-e/QT ratio and the incidence of induced ventricular tachycardia episodes. Amiodarone and AAP10have synergistic effects on upregulating Cx43 and preventing ventricular arrhythmias in this rabbit model of healed myocardial infarction.

OBJECTIVETo investigate the common TCM syndrome types of fatty liver by way of epidemic questionnaire, their occurrence ratio, and the correlation between various syndrome types and objective indexes.

METHODSA total of national wide 503 subjects with fatty liver were enrolled, the TCM syndromes, body mass index (BMI), abdominal perimeter/hip circumference, liver function, blood lipids, B ultrasonic examination and CT in them were observed and recorded.

RESULTSIn the 46 symptoms investigated in total, the first ten symptoms in order of appearing rate were lassitude, obese, oral dryness, vertigo, hypochondriac distending pain, soreness and pain in loin, spiritlessness, oral bitterness, aching and weakness in knee and abdominal distention. The mostly appeared tongue figures were pale and corpulent or pale dim tongue proper, white greasy or yellow greasy tongue coating, and the mostly appeared pulse figures were taut, taut-thin and taut slippery. Statistical cluster analysis showed that syndromes of fatty liver could be typed into 4 TCM types, the asthenia Pi-Shen with Gan-stagnation type, the asthenia Pi-Shen type, the asthenia Pi with phlegm-heat type and the unclassified type. Among them the asthenia Pi-Shen with Gan-stagnation type was the commonest one, which accounted to 62.32%.

CONCLUSIONThe mostly appeared syndrome type of fatty liver was asthenia Pi-Shen with Gan-stagnation type. The TCM pathogenesis of fatty liver was deficiency of origin, mainly deficiency of Shen, involving Pi, with excess superficiality, the turbid-phlegm and blood stasis.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Diagnosis, Differential ; Fatty Liver ; diagnosis ; epidemiology ; etiology ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Surveys and Questionnaires ; Yang Deficiency ; epidemiology ; Yin Deficiency ; epidemiology

OBJECTIVETo summarize the diagnostic and therapeutic experiences of acute mesenteric venous thrombosis (MVT).

METHODSThe clinical data of 27 cases of acute MVT treated between 1983 and July 2007 were analyzed retrospectively.

RESULTSThe courses of disease were from 1 to 14 days (mean, 6.1 days). Eighteen cases (66.7%) had the history of portal hypertension, deep vein thrombosis, acute MVT or other hypercoagulability. The diagnostic sensitivity of ultrasonography, CT, angiography and serum D-Dimer level were 70.6% (12/17), 75.0% (6/8), 100% (6/6), 100% (6/6), respectively. Bowel necrosis occurred in all the 16 cases with bloody ascites. The thrombolytic and anticoagulation therapy are effective in 36.4% of cases (4/11). Twenty-two cases received operation, and resection of necrotic bowel was performed in all and thrombectomy in 3 cases. The main postoperative complications included 3 cases of deep vein thrombosis, 1 acute cardiac infarction, 3 short bowel syndrome. MVT recurred in 4 cases within a week after operation. Eight patients died within a month after confirmed with acute MVT, in which 7 patients died after operation. Anticoagulation medication was implemented in all the 19 survived patients. Fifteen patients were followed-up for 1-120 months (mean, 39.2 months), 7 of them continued the anticoagulation therapy during this period.

CONCLUSIONSThe determination of serum D-Dimer level and such adjuvant examinations as ultrasonography, CT and angiography are important diagnostic means for acute MVT. Anticoagulation and thrombolysis should be considered firstly if there is no active bleeding and bowel necrosis. We recommend laparotomy when bowel necrosis is suspected.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Male ; Mesenteric Veins ; Middle Aged ; Retrospective Studies ; Venous Thrombosis ; diagnosis ; therapy

OBJECTIVETo investigate the effect of KN-93, a calmodulin kinase II inhibitor, on ventricular arrhythmias in rabbits with cardiac hypertrophy.

METHODSFemale New Zealand white rabbits were randomly divided into four groups (n = 10 each): Sham; LVH; LVH + KN-92 and LVH + KN-93 group. LVH was induced by partially constricting the abdominal aorta. In Sham group, the abdominal aorta was exposed without constriction. Eight weeks later, the arterially perfused left ventricular wedge preparations were made and transmembrane action potentials (TAP) from epicardium and endocardium and transmural ECG were simultaneously recorded. Incidence of early after depolarization (EAD) and torsade de pointes (Tdp), QT interval, action potential duration (APD) and transmural depolarization dispersion (TDR) at different cycle lengths were observed under slow stimulation (2000 - 4000 ms), hypokalemic (2 mmol/L) and hypomagnesaemic (0.25 mmol/L) Tyrode's solution perfusion.

RESULTSLeft ventricular hypertrophy was detected in LVH group by echocardiography and not affected by KN-92 and KN-93. Perfused with hypokalemic, hypomagnesaemic Tyrode's solution and under slow stimulation (2000 - 4000 ms), the incidences of EAD and Tdp in Sham group, LVH group, LVH + KN-92 group (0.5 micromol/L) and LVH + KN-93 group (0.5 micromol/L) were 0/10, 10/10, 9/10, 5/10 and 0/10, 5/10, 4/10, 1/10, respectively. With 1 micromol/L KN-92 and KN-93, the incidences of EAD and Tdp in LVH + KN-92 and LVH + KN-93 group were 9/10, 3/10 and 4/10, 1/10 respectively. The QT interval, APD and TDR were not affected by KN-93.

CONCLUSIONThe calmodulin kinase II inhibitor KN-93 can effectively suppress ventricular arrhythmias in rabbits with cardiac hypertrophy by decreasing EAD.

Animals ; Arrhythmias, Cardiac ; complications ; drug therapy ; Benzylamines ; pharmacology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; antagonists & inhibitors ; Cardiomegaly ; complications ; drug therapy ; Disease Models, Animal ; Male ; Protein Kinase Inhibitors ; pharmacology ; Rabbits ; Sulfonamides ; pharmacology

OBJECTIVE:To systematically evaluate therapeutic efficacy and safety of pitavastatin comparison of atorvastatin in the treatment of primary hypedipemia in Chinese adults,and to provide evidence-based reference for clinic.METHODS:Retrieved from The Cochrane Library,PubMed,Chinese Journal Full-text Database,Wanfang database,and manually search Google Scholar,Baidu academic search engine,randomized controlled trials (RCTs) about pitavastatin (trial group) vs.atorvastatin (control group) in the treatment of primary hyperlipemia in Chinese adults were collected.After literature screening,data extraction,quality evaluation of included studies with modified Jadad scale,Meta-analysis of the levels of total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C),response rate and the incidence of ADR was conducted by using Rev Man 5.3 statistical software.RESULTS:A total of 5 RCTs were included,involving 456 patients.Results of Meta-analysis showed that the decrease of TC level [MD=0.09,95％CI(0.01,0.16),P=0.03] in trial group was more better than control group,while the increase of HDL-C level [MD=0.08,95％ CI (0.01,0.14),P=0.03] and the decrease of the TG level [MD=-0.13,95％ CI (-0.20,-0.06),P=0.000 4] in trial group were worse than control group,with statistical significance.There was no statistical difference in the decrease of LDL-C[MD=-0.01,95％ CI (-0.13,0.10),P=0.84],response rate [OR=0.75,95％CI (0.15,3.66),P=0.72] or the incidence of ADR [OR=0.68,95 ％ CI (0.44,1.05),P=0.08] between 2 groups.CONCLUSIONS:Pitavastatin has better therapeutic efficacy in decreasing TC,but its therapeutic efficacy in decreasing LDL-C is similar to that of atorvastatin;its therapeutic efficacy in decreasing TG and increasing HDL-C is worse than that of atorvastatin.The safety of them is equivalent.

OBJECTIVETo investigate the histopathological features in livers of chronic severe hepatitis B (CSHB) patients.

METHODSHistology of 42 livers was studied. HE, Masson, Sweet and D-PAS staining and cytokeratin 7, CD68 and proliferating cell nuclear antigen immuno-histochemical staining were used in the study.

RESULTSIn CSHB, the livers showed massive or submassive necrosis in a background of other histological changes of chronic hepatitis B. The characteristic pictures of these livers were necrosis of all the hepatocytes in some nodules, while in other nodules there were only patchy necroses of the parenchyma. In some other nodules the necrotic hepatocytes were all removed and only the scaffolding stroma remained. Meanwhile, regeneration of hepatocytes and bile ductules were also seen.

CONCLUSIONSThe liver histopathological changes in CSHB are identical, but not of the same degree as those of acute severe and subacute severe hepatitis B. In making differential diagnoses for liver aspiration biopsies of these patients, this fact should be kept in mind.

Adult ; Aged ; Female ; Hepatitis B, Chronic ; diagnosis ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Staining and Labeling ; Young Adult

Human tumor necrosis factor alpha (hTNF-alpha) is one of the most important inflammatory cytokines that acts as a mediator in inflammatory and immune response and plays a key role in host defense against infection. The over expression of hTNF-alpha is associated with serious consequences, such as shock, hypotension, thrombus, septicemia and even death. It has been implicated in many autoimmune and inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, chronic heart failure and septic shock. Inhibiting the bio-activity of hTNF-alpha is one of the strategy for the treatment of these diseases. Compared with traditional recombinant protein drugs, small molecule drugs have many advantages, such as high affinity, low immunogenecity and low cost. Systematic evolution of ligands by exponential enrichment (SELEX) is a powerful method for the selection of oligonucleotides that bind with high affinity and specificity to target proteins. Such oligonucleotides are called aptamers, and are potential therapeutics for blocking the activity of pathologically relevant proteins. To obtain oligonucleotide aptamers specifically binding to TNF, a 40nt random DNA combinatorial library flanked by 31nt fixed sequences was chemically synthesized. The random library was amplified with PCR and subjected to selection by SELEX protocol against hTNFalpha. After incubation of the library with hTNFalpha, the mixture was blotted onto Immobilon-NC transfer membrane. The no-specific binding was washed away and the hTNFa binding aptamers were eluted and detached from the target protein. The eluted oligo nucleotides were amplified with PCR and served as the DNA library for the next round selection. After 12 rounds of such selection, the selected aptamers were cloned to pGEM-T vector. Positive clones were identified by restriction enzyme digestion and DNA sequencing. Oligo DNA were synthesized according to the sequence data and tested for their activities. Binding activity of the aptamers to hTNFalpha were detected by ELISA and dot blot with biotin-streptavidin-horseradish peroxidase system. Mouse L929 cells were used to test the anti-hTNFa activity of the DNA aptamers. The aptamers were incubated with hTNFalpha and added to the L929 cells. The results were read under microscope and with MTT staining. It was shown that these DNA aptamers bound to hTNFalpha with high affinity, and can inhibit the cytotoxicity of hTNFalpha on cell culture. The affinity of these aptamers are different and may related to their structure. These ssDNA aptamers are potential for the treatment and diagnosis of hTNFalpha related diseases.
Animals ; Aptamers, Nucleotide ; chemical synthesis ; chemistry ; genetics ; pharmacology ; Biotin ; chemistry ; Cell Line ; Cell Survival ; drug effects ; Enzyme-Linked Immunosorbent Assay ; Gene Library ; Humans ; Mice ; Protein Binding ; SELEX Aptamer Technique ; methods ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; metabolism ; toxicity

The genetic diversity of 279 indivdiuals from 10 populations in Shandong Province was investigated using inter-simple sequence repeat (ISSR) markers. As a result, 116 bands were amplified by 10 informative and reliable primers, of which 101 were polymorphic loci. A relatively high level of genetic diversity was revealed: PPL = 87.07, He = 0.2697, H0 = 0.3999 (at the species level); PPL = 64.58, He = 0.2004, H0 = 0.3010 (at the population level). A higher level of genetic differentiation was detected among populations with Nei's G(ST) analysis and the analysis of molecular variance (AMOVA; G(ST) = 0.2414, F(ST) = 0.2224). Habitat fragmentation and gene flow may result in genetic differentiation. UPGMA cluster analysis indicated that the four populations from Linshu, Junan, Tancheng and Feixian grouped together, whereas Laiyang populations clustered in an isolated clade. The results showed that a mixed mating system was possibly the main factor influencing the genetic structure of this species. These results, combined with other information about Castanea mollissima, may provide a valuable basis for proposing conservation strategies.
China ; Fagaceae ; genetics ; Genetic Markers ; genetics ; Genetic Variation ; Genetics, Population ; Microsatellite Repeats