Yanghe Huayantang Reverses Tamoxifen Resistance in Breast Cancer Through ER/PI3K/Akt/mTOR Pathway / 中国实验方剂学杂志

Objective:To explore the possible mechanism of Yanghe Huayantang in reversing the drug resistance of breast cancer by observing the effect of Yanghe Huayantang on the transplant tumor of tamoxifen （TAM）-resistant breast cancer and its influences on the interaction pathway of estrogen receptor （ER）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR）. Method:Fifty mice were randomly divided into 5 groups： blank group， model group， Yanghe Huayantang group， everolimus group， and Yanghe Huayantang+everolimus group. The model of kidney deficiency was established by bilateral ovariectomy， and the blank group was treated with sham operation. Three days after the establishment of the model， all the five groups of mice were inoculated with breast cancer TAM drug-resistant cells （MCF-7/TAM^-） to establish breast cancer TAM -resistant transplanted tumor model. After successful modeling， Yanghe Huayantang group received intragastric administration of Yanghe Huayantang （traditional Chinese medicine preparation 20 mL·kg^-1）， everolimus group received intraperitoneal injection of everolimus （10 mg·kg^-1）. Yanghe Huayantang + everolimus group received Yanghe Huayantang by intragastric administration and everolimus by intraperitoneal injection. The blank group and model group received intragastric administration and intraperitoneal injection of phosphate buffer （PBS）. Drug administration was lasted for 28 days in all groups， once a day. After administration， the tumor tissue was separated and weighed， and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of tumor tissue. Immunofluorescence and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of PI3K， Akt， mTOR， ER protein and mRNA in tumor tissue. Result:Compared with the model group， the tumor volume and tumor weight of Yanghe Huayantang group decreased significantly on the 12th， 20th and 28th days （<italic>P</italic><0.01）， and the tumor inhibition rate increased significantly （<italic>P</italic><0.01）.Yanghe Huayantang group significantly reduced the density of tumor cells and caused tumor cell necrosis. Compared with the model group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group inhibited the expression of PI3K， Akt， mTOR protein and mRNA （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the blank group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group all inhibited the protein and mRNA expression of ER， and mRNA expression of ER in Yanghe Huayantang+everolimus group was significantly lower than that in the model group （<italic>P</italic><0.01）. Conclusion:Yanghe Huayantang can inhibit the growth of TAM-resistant breast cancer. The mechanism may be that Yanghe Huayantang can reverse the TAM resistance of breast cancer by down-regulating the expression of key molecules of ER/PI3K/Akt/mTOR cross-signal pathway.

Enhanced effect of guizhi plus Gegen Decoction on learning and memory disorder in LPS induced neuroinflammatory mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the potential effect of Guizhi plus Gegen Decoction (GGD) in improving learning and memory of lipopolysaccharides (LPS) induced neuroinflammatory mice and its possible mechanisms.</p><p><b>METHODS</b>Totally 63 male ICR mice were randomly divided into 5 groups, i.e., the normal control (n = 13), the model group (n = 13), the low dose GGD group (n = 10), the high dose GGD group (n = 14), and the positive control group (n = 13). Mice were intraperitoneally injected with LPS (0.33 mg/kg) to induce Alzheimer's disease (AD) model. Mice in the high and the low dose GGD groups were administered with 12 g/kg or 6 g/kg by gastrogavage for 4 successive weeks. Mice in the control group were intraperitoneally injected with minocycline (50 mg/kg) for 3 days. By the end of treatment LPS were injected 4 h before behavior test each day, and then behavior test was conducted in mice of each group. Effect of GGD on learning and memory of AD mice was observed by using open field test, novel object recognition task, and Morris water maze.</p><p><b>RESULTS</b>Open field test showed there was no statistical difference in the movement time and the movement distance among all groups (P > 0.05), suggesting that LPS and GGD had no effect on locomotor activities of mice. In novel object recognition test, AD mice spent significantly shorter time to explore novel object after they were induced by LPS (P < 0.05), while for AD mice in the low and high dose GGD groups, their capacities for exploration and memory were significantly improved (P < 0. 05, P < 0.01). Results of Morris water maze showed that AD mice exhibited increased escape latency (P < 0.05) and spent much less time in swimming across the original platform (both P < 0.05). However, AD mice in the low and high dose GGD groups had obvious shortened latency and increased time percentage for swimming (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>GGD possessed certain improvement in learning and memory disorder of LPS induced AD mice.</p>

Protective effect of Shenxiong injection on cerebral ischemia-reperfusion injury of rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the protective effect of Shenxiong injection on the cerebral ischemia-reperfusion injury of senile rats.</p><p><b>METHOD</b>Totally 108 Sprague-Dawley (SD) rats were randomly divided into the sham operation group, the model group, the Ni-modipine group and Shenxiong injection groups (low, middle, and high doses). The rat brain ischemia-reperfusion model was established by the middle cerebral artery occlusion (MCAO) method in rats, in order to observe the effect of Shenxiong injection on neurological score and brain infarct volume of rats with cerebral ischemia-reperfusion injury, and determine the contents of NOS, NO, SOD, MDA and LDH in brain tissues. The contents of TNF-alpha and IL-1beta levels in brain tissues were measured by enzyme-linked immunosorbent assay (ELISA) method.</p><p><b>RESULT</b>Shenxiong injection could significantly decrease neurological score, injury degree of brain tissues and brain infarct volume of rats with cerebral ischemia-reperfusion injury, increase the vigor of SOD, decrease the levels of MDA, NO, NOS and LDH, and inhibit IL-1beta and TNF-alpha expressions.</p><p><b>CONCLUSION</b>Shenxiong injection has the obvious protective effect on the brain ischemia-reperfusion injury in rats. Its mechanism may be related to the improvement of neurological function, the reduction of free radical injury, and the inhibition of inflammation factor expression.</p>

Detection of periodontal pathogens from saliva of type 2 diabetic patients in urban area of Beijing / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of periodontal pathogens from saliva of patients with type 2 diabetes mellitus (T2DM), and to characterize the association between the glucose status and periodontal pathogens in oral cavity.</p><p><b>METHODS</b>All the subjects were hypertension patients under regular care at Beijing hypertension prevention and management institute. Whole unstimulated saliva samples were collected from 45 non-diabetic subjects (non-DM group), 80 well-controlled diabetic patients (DM-well group) and 100 poor-controlled diabetic patients (DM-poor group). DNA was extracted from the salivary deposition, Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf) and Treponema denticola (Td) were detected by polymerase chain reaction (PCR) method based on 16SrRNA. Prevalence and quantity of the pathogens under different glucose states were compared and logistic regression model was set to analyze the factors related to each bacterium.</p><p><b>RESULTS</b>The prevalence of Tf in DM-well group and DM-poor group was significantly lower than that of non-DM group [81% (65/80), 80% (80/100) vs 91% (41/45), P = 0.048], meanwhile the quantity of Tf was also lower than that of non-DM group [1.9(2.6), 2.1(5.3) vs 3.4(6.4)] (P > 0.05). With the worsening of glucose control, the quantity of Tf was declining (P = 0.032). However, the prevalence and the quantity of Pg, Td in 3 groups had no statistical differences (P > 0.05). After adjusting age, gender, number of missing teeth and other periodontal parameters, OR of having Tf in saliva from DM-well group and DM-poor group was 0.58 and 0.53, respectively.</p><p><b>CONCLUSIONS</b>Abnormal blood glucose state may affect the colonization of Tf in oral cavity.</p>

Application of regionalized critical neonatal emergency transport system / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the application of the regional critical neonatal emergency transport system (NETS) to provide evidence for the optimization of NETS in Beijing.</p><p><b>METHODS</b>All the transported neonates in four hospitals in Haidian District, Beijing, between January 2009 and September 2010 were enrolled. The relevant clinical information of two referral hospitals was analyzed.</p><p><b>RESULTS</b>The top three conditions requiring transport were pre-term delivery, diseases requiring surgical treatment, and respiratory diseases, which accounted for 33.1%, 18.3%, and 14.8%, respectively. Active transport was performed in 95 cases (66.9%) and passive transport in 47 cases (33.1%). The age distribution of the neonates requiring transport was as follows: <6 hrs after birth (24.1%); 6-12 hrs (9.3%); 12-24 hrs (25.9%); and >24 hrs (40.8%). The mean time for transport from the hospital to a referral ward by ambulance was 28.0±11.1 minutes. Diseases requiring emergency surgical treatment were the leading cause of death, accounting for 53.8% of total deaths. The mortality rate was not significantly different between the neonates aged <6 hrs and ≥6 hrs groups.</p><p><b>CONCLUSIONS</b>Active transport remains the main transport pattern among these four hospitals. Neonates requiring surgical treatment have a high mortality rate, and thus special attention should be paid to their transport.</p>

Clopidogrel metabolism related gene polymorphisms in Chinese patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To detect the single nucleotide polymorphisms of clopidogrel metabolism related genes (CYP2C19, ABCB1 and PON1) in Chinese patients with acute coronary syndrome (ACS) by genotype analysis.</p><p><b>METHODS</b>Genetic analysis was performed in patients admitted to Fuwai Hospital from 2005 to 2008 with ACS within 4 weeks. The detection of polymorphisms was performed by TaqMan real-time PCR method. The alleles genotyped were CYP2C19 *2-*8, *17, ABCB1 C3435T, PON1 Q192R and PON1 L55M. Minor allele frequency (MAF) was calculated. Patients were classified as one of the 5 categories by clopidogrel metabolizer phenotypes as extensive [without any "loss-of-function" (LOF) allele *2-*8 or "gain-of-function" (GOF) allele *17], intermediate (with only one LOF allele), Poor (with two or more LOF alleles), ultra (with one or two GOF alleles) or unknown (with one LOF allele and one GOF allele).</p><p><b>RESULTS</b>A total of 2800 ACS patients were enrolled [mean age (59.0 ± 12.3) years and 2236 males (79.9%)]. There were 74% patients with ST-segment elevation myocardial infarction (STEMI, n = 2072), 22.0% patients with non-ST-segment elevation myocardial infarction (NSTEMI, n = 617) and 4.0% patients with unstable angina (UA, n = 111). The minor allele frequency (MAF) for each genotype of CYP2C19 *2, *3, *4, *17 was 28.7%, 4.6%, 0.1% and 1.2%, respectively. There was no LOF allele *5-*8 in the study population. The MAF for ABCB1 C3435T, PON1 Q192R and PON1 L55M was 39.4%, 37.8% and 4.4%, respectively. Clopidogrel metabolizer groups were defined as extensive in 41.7%, intermediate in 45.6%, poor in 10.3%, ultra in 1.9% and unknown in 0.6% patients, respectively. There were no significant differences for all genotypes between males and females. Total LOF carriers of CYP2C19 were 56.4% and GOF carriers were 2.5%.</p><p><b>CONCLUSIONS</b>Our study demonstrated a high distribution of the LOF allele of CYP2C19 in China ACS population.</p>

Association of psychological risk factors and acute myocardial infarction in China: the INTER-HEART China study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Most data about psychological factors relating to acute myocardial infarction (AMI) were obtained from studies carried out in western countries. Results from small descriptive cross-sectional studies in China were inconclusive. The aim of this study was to explore possible associations between psychological risk factors and AMI among the Chinese population with a large-scale case-control study.</p><p><b>METHODS</b>This study was part of the INTER-HEART China study, itself part of the large international INTER-HEART study of cardiovascular risk factors. In this case-control study, 2909 cases and 2947 controls were recruited from 17 cities. Psychological stress, negative life events, depression and controllability of life circumstances were assessed.</p><p><b>RESULTS</b>Cases reported more psychological stress at home or work and odds ratios (ORs) were 3.2 (95%CI 2.1 - 4.9) for permanent stress and 2.1 (95%CI 1.5 - 2.8) for several periods of stress respectively. More cases experienced depression compared with controls (19.6% vs. 9.3%) and ORs were 2.2 (95%CI 1.9 - 2.6). Subjects with 1, 2 and 3 or more depressive symptoms had increased risk of AMI by 2.1, 2.2 and 2.6 fold, respectively, i.e., more depressive symptoms were associated with higher risks of AMI (P for trend < 0.0001). Women had a greater risk of AMI from depression (OR 3.0, 95%CI 2.2 - 4.0) compared to men (OR 2.0, 95%CI 1.6 - 2.4), P for interaction = 0.0364. Negative life events in subjects were associated with increased risk of AMI, OR 1.7 (95%CI 1.4 - 2.0) for one event and 1.8 (95%CI 1.3 - 2.4) for two or more events. High levels of controllability of life circumstances reduced the risk for AMI (OR 0.8, 95%CI 0.7 - 1.0).</p><p><b>CONCLUSIONS</b>Several psychological factors were closely associated with increased AMI risk among Chinese population. Psychological stress had a greater AMI risk in men but depression was more significant among women.</p>

Effect of GBE50 on delayed rectifier potassium current of ventricular myocytes in ischemic guinea pig / 中国应用生理学杂志

<p><b>OBJECTIVE</b>Ginkgo biloba extract 50 (GBE50) is a new multicomponent drug with a polyvalent action extracted from the leave of Ginkgo biloba. The aim of this experiment was to study the effects of GBE50 on delayed rectifier potassium current (I(K)) in ventricular myocytes under normal and simulated ischemia conditions in guinea pigs.</p><p><b>METHODS</b>Single ventricular myocytes were isolated by an enzymatic dissociation method. I(K) were recorded by whole-cell patch clamp technique in voltage clamp mode. GBE50 was added to the perfusion chamber from low to high concentrations (25, 50,100 mg/L) in normal condition. Different concentrations of GBE50 (25, 50, 100 mg/L) were prepared with simulated ischemic fluid.</p><p><b>RESULTS</b>(1) Under normal condition, 100 mg/L GBE50 decreased I(K) (n = 7, P < 0.05). (2) Under ischemia condition, it was observed that I(K) was inhibited (n = 8, P < 0.05). (3) Perfusion with ischemia solution containing 50 mg/L (n = 8, P > 0.05) and 100 mg/L GBE50 (n = 6, P > 0.05) could reverse the decrease of I(K).</p><p><b>CONCLUSION</b>GBE50 significantly decreased I(K) in a concentration-dependent manner. GBE50 could alleviate the electrophysiological heterogeneity of myocardium to prevent ischemic myocardium from arrhythmia.</p>

Impact on the risk of obesity due to interactions between fat mass- and obesity-associated gene rs9939609 variants and behavioral factors, in the Chinese school-aged children / 中华流行病学杂志

Objective To investigate how the interactions between fat mass- and obesityassociated (FTO) gene rs9939609 variants and daily-life related behavioral factors would influence the risk of obesity among the Chinese school-aged children. Methods 3503 school-aged children were selected from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study, and divided into obese children (n=1229) and non-obese children (n=2274). Venipuncture blood test,genotyping and questionnaire were performed. Results Five common factors including protein foods, tobacco & alcohol, vegetables & fruits, sedentary behavior and physical exercise in spare time were extracted with factor analysis methodology. Data from logistic regression analysis showed that taking the interaction of rs9939609 variant with protein foods as an example, the risk of interaction accounted for 19.16% when both factors existing simultaneously. Similarly, the interactions of this SNP with vegetables & fruits, sedentary behavior and physical exercise in spare time appeared to be 5.97%, 19.62% and 12.43% respectively; however there might not be interaction between tobacco,alcohol and the SNP in the Chinese children. Conclusion Protein foods, vegetables & fruits,sedentary behavior and physical exercise might modify the effects of FTO rs9939609 variant on the risk of obesity in Chinese school-aged children. However, large-scale, prospective studies with detailed information on related behavioral factors would be ideal models for identifying the interactions between genes and environment.

Levels of tumor necrosis factor-alpha and interleukin-1beta in saliva of metabolic syndrome patients / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the association between periodontitis and the low-grade inflammation in metabolic syndrome (MS) patients.</p><p><b>METHODS</b>Fifty-seven MS patients, 26 healthy controls were enrolled. Non-stimulated whole saliva was collected. The levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta was analyzed by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Concentration of cytokines was compared between MS patients and the healthy controls. Correlations between the cytokines and various periodontal indices, and between the cytokines level and different quantity of metabolic syndrome components were also investigated.</p><p><b>RESULTS</b>Levels of TNF-alpha in saliva of MS patients [(69.30+/-21.01) ng/L] were significantly higher than that in the healthy subjects [(57.85+/-15.69) ng/L, P<0.05], and of IL-1beta in MS patients [(616.42+/-360.05) ng/L] higher than that in healthy subjects [(506.06+/-245.76) ng/L], but the difference was not statistically significant. TNF-alpha was positively correlated with bleeding index (BI). In MS patients, TNF-alpha level and IL-1beta level increased with increasing severity of periodontal disease and increasing component numbers of MS.</p><p><b>CONCLUSIONS</b>Periodontal inflammation may be one of the sources of low-grade inflammation in MS patients. Both systemic and periodontal conditions may influence the level of salivary TNF-alpha and IL-1beta.</p>

Expression of E-cadherin catenin complex and invasiveness of pituitary adenoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore the relationship between the E-cadherin catenin complex and invasiveness of pituitary adenoma.</p><p><b>METHODS</b>The expression of E-cadherin catenin complex was determined by immunohistochemistry in 78 cases of human pituitary adenomas including invasive adenoma 44 cases, noninvasive adenoma 34 cases and the relativity of their expressions with hormone-producing, pituitary apoplexy and necrosis or cystoid change, tumor diameter were analyzed.</p><p><b>RESULTS</b>The invasive group had a significantly lower expression of E-cad and alpha-cat than that of noninvasive group (chi-squared = 13.969, P < 0.01). There was no statistical significance for beta-cat expression between the invasive group and noninvasive group (chi-squared = 0.430, P > 0.05). Moreover, the expressions of beta-cad and alpha-cat were significantly lower in macro-adenoma group than that in micro-adenoma group (chi-squared = 5.038, P < 0.05). The expression of E-cad was significantly lower in endocrine inactive group than that in endocrine active group (chi-squared = 4.614, P < 0.05). The expression of beta-cat was significantly lower in the group with apoplexy and necrosis than that in the group without apoplexy and necrosis (chi-squared = 6.701, P < 0.05).</p><p><b>CONCLUSIONS</b>The reduction of E-cad catenin complex is related to invasiveness and clinical pathological characteristics.</p>

Suppression of c-myc expression by interference RNA in HepG2 hepatocellular carcinoma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of RNA interference (RNAi) on c-myc expression in hepatocellular carcinoma cell line, HepG2.</p><p><b>METHODS</b>Expression vector of c-myc gene-targeting small interference RNA (siRNA) was constructed (psilencer-c-myc) and transfected into HepG2 cells by lipofectamine, and the unloaded vector was used as control (mock). The expression of c-myc mRNA and protein was identified by quantitive PCR and Western blot. Apoptosis of the transfected cells was examined by flow cytometry and immunofluorescent microscopy.</p><p><b>RESULTS</b>After HepG2 cells were transfected with psilencer-c-myc, the expression of c-myc mRNA and protein was suppressed with an inhibition rate of 67% compared with the mock-transfected cells. Apoptosis was identified in the transfected HepG2 cells.</p><p><b>CONCLUSION</b>The expression of c-myc at transcriptional and translational levels in HepG2 cells transfected with siRNA is markedly inhibited, which may be associated with the induction of apoptosis.</p>