A calcium-sensing receptor polymorphism at E942K promotes the proliferation of gastric cancer cells via Ca and ERK1/2 pathways / 生理学报

The study was designed to investigate the effects and mechanism of a calcium-sensing receptor (CaSR) polymorphism at E942K on the proliferation of gastric cancer cells. Single nucleotide polymorphisms (SNPs) were detected between gastric cancers group and normal controls group by DNA sequence analysis. The cell model was constructed by transfection of E942K mutant plasmid and wild-type (WT) plasmid into SGC-7901 and HEK-293 cells. The effect of E942K mutation on cell proliferation ability was detected by CCK8 and cell clone formation experiments. The effect of E942K mutation on calcium signaling was detected by calcium imaging. Western blot experiments were used to detect changes in phosphorylation levels of key proteins ERK1/2 and β-catenin in downstream signaling pathways after E942K mutation. The results showed that the mutation rate of E942K in gastric cancer group was significantly higher than that in normal control group (P < 0.05). CCK8 and cell clone formation experiments showed that E942K mutation significantly improved the proliferation ability of SGC-7901 gastric cancer cells and HEK-293 cells. E942K mutation enhanced calcium signaling in SGC-7901 and HEK-293 cells. E942K mutation enhanced ERK1/2 phosphorylation without affecting β-catenin phosphorylation. The results suggest that E942K mutation in CaSR may ultimately promote the proliferation of gastric cancer cells by enhancing intracellular calcium signaling and ERK1/2 phosphorylation. These results have potential clinical implications for the diagnosis and targeted therapy of gastric cancer.

Mechanism of Modified Taohe Chengqitang in Treating Diabetic Gastroparesis Based on Network Pharmacology / 中国实验方剂学杂志

<b>Objective::To study the mechanism of modified Taohe Chengqitang in preventing and treating diabetic gastroparesis by regulating relative genes and signaling pathways based on network pharmacology. <b>Method::Target genes of modified Taohe Chengqitang were obtained from Bioinformatics Analysis Tool for Molecular Mechanism of TCM (BATMAN-TCM) database, and target genes of diabetic gastroparesis were obtained from Comparative Toxicogenomics Database (CTD) database. The target genes of modified Taohe Chengqitang-diabetic gastroparesis intersection protein were obtained through the integration of two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. Cytospace software ClueGO, CluePedia plug-in were used for gene ontology (GO) analysis and enrichment analysis of KEGG pathway of modified Taohe Chengqitang-diabetic gastroparesis target genes intersection, and results were visualized. Finally, CTD database and literatures were used to obtain intersection genes in the treatment of diabetic gastroparesis. <b>Result::Among 621 target genes in modified Taohe Chengqitang, 25 were related to diabetic gastroparesis. By regulating expressions of MLNR, SST, PTGS1, HRH2, HTR3A, HTR4, HTR7, NOS3 and other intersection genes, Taohe Chengqitang could improve the gastrointestinal hormone levels, affected the combination of serotonin and its receptors, activated adenylate cyclase (AC), and induced cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), so as to activiate AC/cAMP/PKA signaling pathway, regulate Ca²⁺ /K⁺ channel, control ion balance, promote the adaptability of gastric smooth muscle, and contract gastric smooth muscle to regulate gastric volume. At the same time, gastric acid secretion was improved to protect gastric mucosa, which may help improve vasoconstriction and hemodynamics. <b>Conclusion::Based on the network pharmacology, modified Taohe Chengqitang has multiple mechanisms in the prevention and treatment of diabetic gastroparesis. This study explored relevant signaling pathways, advantages and research directions of modified Taohe Chengqitang in treatment of diabetic gastroparesis.

Bivariate heritability estimation of resting heart rate and common chronic disease based on extended pedigrees / 北京大学学报(医学版)

OBJECTIVE@#To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes.@*METHODS@#The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables.@*RESULTS@#The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05).@*CONCLUSION@#Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.

Natural Law and Pathogenesis Based on Wufang Circular Motion / 中国实验方剂学杂志

Various academic discussions have been officially proposed in the " theory of circular motion" in Circular Motion of Ancient Chinese Medicine. The theory of circular motion reflects the inheritance and development of the theory of Yin-Yang and five elements in ancient Chinese medicine, which has a great significance in the modern basic theory research and clinical practice of traditional Chinese medicine. On the basis of ancient literatures, this article aims to discuss the natural law of circular motion from the perspectives of the path of sun and 24-solar-terms of seasons via five-elements and Wufang circular motion theory according to circular motion. The circular motion has an effect on human body and natural environment. The invasion of pathogen is caused by deficiency of essential Qi. The combination of the healthy-Qi deficiency with the deficiency-type pathogen leads to the occurrence of external contraction. Therefore, the abnormality of Yang-Qi including nature and human is the main cause of the disease's development. Because the circular motion can expound the change rule and mutual relations of nature and human, we can predict the development of disease by it. When the circulation motion is disordered, clinical symptoms appear with inner pathogenesis. The understanding of the change of the circulation motion is helpful for us to have a deeper realization of the disease, grasp the pathogenesis and provide treatment based on syndrome differentiation. The authors explain nature environment and human physiology, and elaborate the relations between natural rule and Wufang's effect on circulation motion, in order to provide certain suggestions to guide clinical treatment based on pathogenesis.

Mechanism of Modified Taohe Chengqitang in Treating Diabetic Nephropathy Based on Network Pharmacology / 中国实验方剂学杂志

Objective: To study the mechanism of modified Taohe Chengqitang in preventing and treating diabetic nephropathy by means of network pharmacology. Method: Target genes of modified Taohe Chengqitang were obtained from BAT-MAN database, while target genes of diabetic nephropathy were obtained from CTD database. The target genes of disease-drug protein were obtained by crossing two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. The key genes were screened out through the computational analysis algorithm of network structure and weighted relatedness between nodes. With DAVID online tools, gene ontology (GO) analysis of Disease-Drug Intersection Target Genes and enrichment analysis of kyoto encyclopedia of genes and genomes(KEGG) pathway were conducted. Finally, CTD database and literature study were used to obtain the key genes in the treatment of diabetic nephropathy. Result: Among 621 compounds in modified Taohe Chengqitang, 581 of them were related to diabetic nephropathy. NOS3, OAT, NT5C2, ACACB, AGXT, PDE3B and other key genes mainly regulated nerve tissue transmission, cholinergic synaptic pathway, calcium channel, metabolic pathway, purine metabolic pathway, angiotensin-neurosynaptic pathway, cyclic guanosine monophosphate/cGMP-dependent protein kinase G (cGMP/PKG) signaling pathway and cyclic adenosine phosphate signaling pathway, with effect in molecular reactions, such as plasma membrane, postsynaptic membrane and mitochondria. Conclusion: The network pharmacology predicts the key targets of modified Taohe Chengqitang in the prevention and treatment of diabetic nephropathy and the related pathways involved, suggesting a multi-target, multi-channel and multi-choice complex mechanism, and which is mostly related to anti-inflammation, oxidative phosphorylation and purine metabolism.

Relationship between methylation of SOX11 gene and cervical cancer / 西安交通大学学报(医学版)

Objective: To detect the methylation status of SOX11 gene in normal cervix, cervical cancer tissues and cervical cancer cell lines so as to explore the relationship between methylation status and expression of SOX11 gene. Methods: DNA methylation status of SOX11 gene in normal cervical, cervical cancer tissues and cervical cancer cell lines was analyzed by bisulfite sequencing and TA cloning assay. The expression of SOX11 mRNA in cervical cancer tissues, cell lines and normal cervical was detected by RT-PCR. Results: The average methylation rate of SOX11 in cervical cancer tissues (81.07%) was significantly higher than that in normal cervical tissues (12.86%) (P<0.001). The methylation status of SOX11 in HeLa, SiHa, C33-A and CaSki cells was all hypermethylated with the methylation of 90.71%, 97.14%, 77.14% and 99.64%, respectively. The expression of SOX11 mRNA in cervical cancer tissues was significantly lower than that in normal cervixes (P<0.001). The SOX11 gene expression was significantly negatively correlated with its promoter hypermethylation (P<0.001, r=-0.808). After demethylation agent 5-azacytidine treatment, SOX11 mRNA expression in cervical cancer cell lines was significantly increased. Further analysis showed that HPV infection in cervical cancer might increase SOX11 promotor methylation. Conclusion: SOX11 gene in cervical cancer is silenced by the hypermethylation of DNA in the promoter region.

Estrogen regulates osteogenic differentiation of human periodontal ligament stem cells via Wnt/beta-catenin signaling pathway / 中国组织工程研究

BACKGROUND: Estrogen can promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), but the molecular mechanism is unclear. OBJECTIVE:To study the regulatory effect of estrogen on the osteogenic differentiation of hPDLSCs via Wnt/β-catenin signaling pathway. METHODS: The hPDLSCs were isolated and purified by digestion method combined with limited dilution clone method. Three experimental groups were set as follows: osteogenic induction only (control group); 1×10-7mol/L estrogen with osteogenic induction (estrogen group); and 100 μg/L Wnt3a protein with osteogenic induction (Wnt3a group). Alkaline phosphatase activity was detected at 1, 3, 5, 7 days of osteogenic induction. Western blot was used to detect the expression of Wnt/β-catenin signaling pathway related proteins β-catenin, P-GSK-3β, GSK-3β, CyclinD1 and osteoblast-related proteins Runx2 and OCN after 7 days of osteogenic induction. RESULTS AND CONCLUSION: The activity of ALP in all groups increased with time. The expression level of ALP in the estrogen group and Wnt3a group was higher than that in the control group at 1, 3, 5 and 7 days of induction (P < 0.05), while there was no significant difference between the former two groups (P > 0.05). The western blot results showed that the expression levels of β-catenin, P-GSK-3β, CyclinD1, Runx2 and OCN in the estrogen group and Wnt3a group were higher than those in the control group (P < 0.05), while the expression of GSK-3β was lower than that in the control group (P < 0.05). But there were no differences in the expression of Wnt/β-catenin signaling pathway related proteins and mid-late osteogenic markers between estrogen group and Wnt3a group (P > 0.05). To conclude, estrogen can enhance the osteogenic differentiation of hPDLSCs, and the underlying mechanism is likely to activate the Wnt/β-catenin signaling pathway in activated hPDLSCs exposed to estrogen.

Combined oral contraceptives facilitate periodontium remodeling during orthodontic tooth movement in rats / 中国组织工程研究

BACKGROUND: Preliminary studies have found that the oral intake of contraceptives reduces the rate of orthodontic tooth movement. This study mainy explores the effects of oral contraceptives on periodontium remodeling during orthodontic tooth movement in a female rat model. OBJECTIVE: To investigate the effects of combined oral contraceptives (COCs) on the expression levels of progesterone receptor and osteoprotegerin, as well as the number of osteoclasts in the periodontium during orthodontic tooth movement. METHODS: Eighty 3-month-old female Sprague-Dawley rats were randomly divided into two groups (n=40 per group), and COCs (marvelon, experimental group) or normal saline (control group) was then given by gavage. At 7 days after administration, the right maxillary first molars were moved mesially under a force of 50 g delivered by nickel-titanium coil springs, and 10 rats were killed on day 7, 14, 21 and 28 after loading, respectively. The expression levels of progesterone receptor and osteoprotegerin in the periodontium were detected by immunohistochemistry, and the number of activated osteoclasts was measured by tartrate-resistant acid phosphatase staining. RESULTS AND CONCLUSION: At 28 days after force loading, the expression level of progesterone receptor in the periodontium in the experimental group (0.307±0.03) was significantly higher than that in the control group (0.194±0.11), (P < 0.01). The number of osteoclasts in the maxillary first molars in the experimental group was significantly less than that in the control group at 7, 14, 21 and 28 days after force loading (P < 0.05). The average absorbance value of osteoprotegerin in the experimental group was significantly higher than that in the control group (P < 0.01). These results show that COCs are able to promote osteogenesis and slow bone absorption during periodontal reconstruction, indicating that the course of orthodontic treatment for female patients with a history of COCs intake may be extended.

Time-dependent expression of PEDF and VEGF in blood serum and retina of rats with oxygen-induced retinopathy / 华中科技大学学报（医学）（英德文版）

The effects of the balance changes of pigment epithelium growth factor (PEDF) and vascular endothelial growth factor (VEGF) in whole-body and retinal tissue on rats with oxygen-induced retinopathy were investigated. Forty-eight neonatal SD rats at the age of 7 days were randomly divided into 4 groups. The neonatal rats in experimental groups were exposed to 75% to 80% oxygen for 5 days and then to normal air, and those in control groups were kept feeding in normal air. At the age of 17 and 22 days, all the neonatal rats received retina angiography with FITC-dextran and the pathological changes of retinal vessels and perfusion were observed. HE staining of the tissue section and the number counting of endothelial cells extending beyond the inner limiting membrane were performed to evaluate the endothelial proliferation. Immunohistochemistry was applied to detect the expression of PEDF and VEGF in retinal tissue, and ELISA to detect their expression in serum. A hypoxic-ischemic proliferation of retina and more endothelial cells extending beyond the inner limiting membrane were found in the neonatal rats in both experimental groups of 17-day old and 22-day old as compared with those in control group with the difference being statistically significant (P0.05). The serum PEDF concentration in the rats of 17 days old in experimental group was decreased significantly as compared with that in the rats of 17 days old in control group (P<0.01), and in experimental groups, the serum PEDF concentration of the rats of 22 days old was increased as compared with that of the rats of 17 days old (P<0.01). In conclusion, the obviously decreased serum PEDF concentration and the abnormal enhanced expression of VEGF density in local retinal tissue broke down the balance of PEDF/VEGF in whole-body or local tissues, which might play an important role in retinal vascular proliferation.

Time-dependent expression of PEDF and VEGF in blood serum and retina of rats with oxygen-induced retinopathy / 华中科技大学学报（医学）（英德文版）

The effects of the balance changes of pigment epithelium growth factor (PEDF) and vascular endothelial growth factor (VEGF) in whole-body and retinal tissue on rats with oxygen-induced retinopathy were investigated. Forty-eight neonatal SD rats at the age of 7 days were randomly divided into 4 groups. The neonatal rats in experimental groups were exposed to 75% to 80% oxygen for 5 days and then to normal air, and those in control groups were kept feeding in normal air. At the age of 17 and 22 days, all the neonatal rats received retina angiography with FITC-dextran and the pathological changes of retinal vessels and perfusion were observed. HE staining of the tissue section and the number counting of endothelial cells extending beyond the inner limiting membrane were performed to evaluate the endothelial proliferation. Immunohistochemistry was applied to detect the expression of PEDF and VEGF in retinal tissue, and ELISA to detect their expression in serum. A hypoxic-ischemic proliferation of retina and more endothelial cells extending beyond the inner limiting membrane were found in the neonatal rats in both experimental groups of 17-day old and 22-day old as compared with those in control group with the difference being statistically significant (P<0.01). VEGF staining of the rats in the 17-day old experimental group was significantly stronger, with an increasing positive rate, than that of the rats in the 17-day old control group (P<0.01). PEDF staining of the rats of 22 days old was weaker than that of the rats of 17 days old in the experimental groups (P<0.01). There was no significant difference in serum VEGF concentration among all groups (P>0.05). The serum PEDF concentration in the rats of 17 days old in experimental group was decreased significantly as compared with that in the rats of 17 days old in control group (P<0.01), and in experimental groups, the serum PEDF concentration of the rats of 22 days old was increased as compared with that of the rats of 17 days old (P<0.01). In conclusion, the obviously decreased serum PEDF concentration and the abnormal enhanced expression of VEGF density in local retinal tissue broke down the balance of PEDF/VEGF in whole-body or local tissues, which might play an important role in retinal vascular proliferation.

Regulation of 18β-glycyrrhetinic acid on apoptosis of U937 cell through activation of Wnt/β-catenin signal / 中国药学杂志

OBJECTIVE: To explore the regulation of 18β-glycyrrhetinic acid on apoptosis of human acute leukemia U937 cell through Wnt/β-catenin signal.

Urokinase-type plasminogen activator receptor as a predictor of poor outcome in patients with systemic inflammatory response syndrome / 世界急诊医学杂志（英文）

BACKGROUND:Urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator receptor (uPAR) are known as important factors, which mediate a variety of functions in terms of vascular homeostasis, inflammation and tissue repair. However, their role in systemic inflammatory response syndrome (SIRS) has been less well studied. This study aimed to test the hypothesis that the abnormalities of fibrinolysis and degradation of extracellular matrix mediated by uPA and uPAR are directly related to the patients with SIRS. We therefore analyzed their role and clinicopathological significance in patients with SIRS.METHODS:A case-control study was conducted with 85 patients who were divided into two groups according to the diagnostic criteria of SIRS:SIRS group (n=50) and non-SIRS group (n=35). The SIRS group was divided into MODS group (n=26) and non-MODS group (n=24) by their severity, and survival group (n=35) and non-survival group (n=15) by their prognosis. Another 30 healthy adults served as normal controls. uPA and uPAR in plasma were detected by commercial enzyme-linked immunosorbent assay (ELISA) kits.RESULTS:The plasma level of uPA was lower in the SIRS group than in the non-SIRS group and controls (P<0.001 andP<0.001). It was lower in sepsis patients and the MODS group than in the non-sepsis patients and the non-MODS patients (allP<0.05). However, there was no difference in uPA level between survivors and non-survivors (P>0.05). The plasma level of uPAR increased in the SIRS group compared with the non-SIRS group and controls (P<0.001 andP<0.001). There was a significant elevation of uPAR in sepsis patients, MODS patients and non-survivors as compared with non-sepsis patients, non-MODS patients and survivors respectively (allP<0.05). Plasma uPAR levels were positively correlated with APACHE II score (r=0.575,P<0.001) and SOFA score (r=0.349,P=0.013). AUCs for the prediction of SIRS mortality were 0.67 and 0.51, respectively, for uPA and uPAR.CONCLUSION:uPAR could be a predictor of poor outcome in patients with SIRS.

Influence of different T cell activators on the expression of Foxp3 in bronchial asthma / 中华实用儿科临床杂志

Objective To explore the influence of different T cell activators on the expression of Foxp3 in bronchial asthma.Met-hods Peripheral blood monouclear(PBMCs) were isolated from the 30 children suffering from mild persistent asthma allergic to house dust mite (HDM).PBMCs of those children were divided into 2 groups.One group was stimulated with HDM extracts (HDM group) and the other was stimulated with phorbol-12-myristate-13-acetate (PMA) extracts (PMA group).After 48 hours of in vitro stimulation with HDM extracts or PMA extracts,the levels of CD4 + CD25 + T cells,CD4 + CD25 + Foxp3 + T cells and CD4 + CD25 + Foxp3 + IL-10 + T cells were measured by flow cytometry.Results The levels of CD4 + CD25 + T cells significantly decreased in the HDM group[(4.59 ± 1.10) ％] compared with those in the PMA group[(41.24 ±7.95)％] (P ＜0.0001).The levels of CD4+ CD25 + Foxp3 + T cells significantly decreased in the HDM group [(18.08 ± 1.82) ％] compared with those in the PMA group [(90.26 ± 3.63) ％] (P ＜ 0.0001).The levels of CD4 + CD25 + Foxp3 + IL-10 + T cells had no statistical significance in the HDM group [(37.62 ± 3.23) ％] compared with those in the PMA group [(38.33-± 3.95) ％] (P ＞ 0.05).Conclusion Nonspecific T cell activators can increase the expression of Foxp3 in bronchial asthma.

Prognostic significance of urokinase-type plasminogen activator and its receptor in patients with systemic inflammatory response syndrome / 世界急诊医学杂志（英文）

BACKGROUND: This study aimed to determine the plasma levels of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), D-dimer, IL-6 and TNF-α, and observe the relations among uPA, uPAR, D-dimer, IL-6 and TNF-α in patients with systemic inflammatory response syndrome (SIRS). METHODS: A prospective, clinical case-control study was conducted in patients with SIRS at age of more than 55 years old treated during 2008-2010 at Wuhan Central Hospital. Venous blood samples were collected by routine venipuncture. Eighty-five patients were divided into two groups according to diagnostic criteria of SIRS: SIRS patients from intensive care units (n=50), and non-SIRS patients from medical wards (n=35). Thirty healthy blood donors who visited the General Health Check-up Division at Wuhan Central Hospital served as controls. Excluded from the study were (1) those patients with pregnancy; (2) those with cancer; (3) those died after admission into the ICU in 7 days; (4) those received cardiopulmonary resuscitation; (5) those who had previous blood system diseases; and (6) those with SIRS before admission into the ICU. The levels of uPA, uPAR, D-D, IL-6 and TNF-α in blood were detected by commercial enzyme-linked immunosorbent assay (ELISA) kit. The data were analyzed using SPSS version 17.0 and expressed as mean ± standard. Student's t test and the Mann-Whitney U test were used in the analysis. The relations of uPA, uPAR and D-dimer, IL-6 TNF-α levels were analyzed using Spearman's rank-order correlation coefficient test. RESULTS: The plasma levels of uPA , uPAR, D-dimer,IL-6 and TNF-α in the patients with SIRS were obviously higher than those in the non-SIRS patients and controls (P<0.001). Correlation analysis showed a positive correlation between uPAR and IL-6 levels (r=0.395, P=0.004) and between uPAR and TNF-α levels (r=0.606, P<0.001), but no correlation between uPAR and D-dimer levels (r=0.069, P=0.632). No correlation was observed between uPA, D-dimer, IL-6 and TNF-α levels (P>0.05). The establishment of ROC curve was based on the levels of uPAR, D-dimer, IL-6 and TNF-αin 24 hours for the diagnosis of multiple organ dysfunction syndrome (MODS), and the ROC areas under the curve were 0.76, 0.58, 0.86 and 0.83, respectively. CONCLUSIONS: uPA and uPAR play a major role in patients with SIRS in the process of coagulation disorder, but the mechanism of SIRS is not the same. uPAR may play a central role in the development of SIRS to MODS.

Effect of docetaxel-loaded lipid microbubbles combined with ultrasound targeted microbubbles destruction on microvessel of rabbit VX2 liver tumor models / 中国介入影像与治疗学

ObjectiveTo observe the inhibition effect of docetaxel-loaded lipid microbubbles (DLLM) combined with ultrasound targeted microbubbles destruction (UTMD) on microvessel in rabbit VX2 liver tumor models.MethodsSixty rabbits were randomly divided into 6 groups (n= 10),i.e.Doc group (used docetaxel only),DLLM group (used docetaxel-loaded lipid microbubbles),Doc+US group (used docetaxel combined with ultrasound positioning irradiation),PLM+US group (used microbubbles combined with ultrasound positioning irradiation),DLLM+US group (used docetaxel-loaded lipid microbubbles combined with ultrasound positioning irradiation) and control group.The expression of CD34 and VEGF and microvessel density (MVD) were compared among different groups.ResultsAfter treatment,the expression of CD34 in DLLM+US group was lower,the MVD of DLLM+US group was markedly lower than that of the other groups (P＜0.01),while the expression of VEGF in this group was the lowest among all 6 groups (P＜ 0.01).ConclusionDLLM combined with UTMD can inhibit the generation of microvessels in rabbit VX2 liver tumor,thus inhibit the growth of the tumor.

Effects of paclitaxel loaded ultrasound contrast agents on cell cycles and ultrastructural features of HepG2 cells / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the effects of paclitaxel loaded ultrasound contrast agents on cell cycles and ultrastructural features of HepG2 cells.</p><p><b>METHODS</b>HepG2 cells were cultured, and divided into a blank control group, a paclitaxel group, an ultrasound contrast agents group, and a paclitaxel loaded ultrasound contrast agents group. Cell cycles of the four groups were detected by flow cytometry, and the ultrastructural changes of the cells were observed under a transmission electron microscope.</p><p><b>RESULTS</b>Paclitaxel loaded ultrasound contrast agents blocked the HepG2 cells at their G2/M phases, and it also induced more apoptosis of the HepG2 cells.</p><p><b>CONCLUSIONS</b>Paclitaxel loaded ultrasound contrast agents can block HepG2 cells at the G2/M phase and induce apoptosis of the cells.</p>

Postmenopausal bleeding:a clinical analysis of 210 cases / 中国基层医药

Objective To investigate the causes,diagnostic methods,prevention and cure of postmenopausal bleeding(PMB).Methods The clinical and pathological data of 210 PMB patients admitted in this hospital were retrospectively analyzed.Results The causes for PMB were benign diseases(69.5%),the most of which were infec- tious diseases(49.5%),non-organic disease(20.5%)and malignant tumor(10.0%).Compared with benign diseases and non-organic diseases,the attack age of malignant tumor was higher[(67.1?6.9)years old],menopausal dura- tion was longer(11.6?2.9)years,bleeding duration was longer[(157.6?26.4)days],and mucous membrane was obviously thickened[(14.6?3.2)mm](P0.05).Conclusion The main cause for PMB is benign diseases,followed by non-organic diseases.More attentions should be paid to the PMB patients with higher attack age,longer menopausal duration and bleeding dura- tion,and obviously thickened mucous membrane,so as to be precautions to the occurrence of malignant tumor.

DNAzymes in vitro inhibit the expression of hepatitis B virus genes / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the inhibition effects of DNAzymes specific to Hepatitis B Virus(HBV) s gene and e gene on the expressions of Hepatitis B surface antigen(HBsAg) and Hepatitis B e antigen(HBeAg).</p><p><b>METHODS</b>DNAzymes DrzBS and DrzBC specific to HBV s gene ORF A157UG and e gene ORF A1816UG, respectively, were designed and synthesized. The inhibition effects of DrzBS or DrzBC on the expressions of HBV s and e genes were observed in 2.2.15 cells.</p><p><b>RESULTS</b>The expression of HBV s or e genes was dramatically depressed after 2.2.15 cells treated by DrzBS or DrzBC. The concentration for effective inhibition was within 0.1-2.5 micromol/L and the inhibition showed a dose dependence within that concentration range. The maximum inhibition was 94.2% and 91.8% for DrzBS and DrzBC, respectively. The inhibition was maintained for 72 hours. The efficiency of inhibiting HbsAg, HbeAg in 2.2.15 cells by DrzBS, DrzBC was higher than that by antisense oligonucleotides for the same target genes. The concentrations for effective inhibition of the DNAzymes were at least 10-fold lower compared with antisense oligonucleotides. Neither inhibition on the replication of HBV DNA nor toxicity to 2.2.15 cells was observed.</p><p><b>CONCLUSION</b>DrzBS and DrzBC can highly block the expressions of HBV s gene and e gene in 2.2.15 HBV cell model and are proved a specific and effective anti-HBV gene therapeutic means.</p>

Experimental study of the therapeutic effectiveness of defibrase on treating acute cerebral ischemia and the effectiveness in different administrated ways / 中国康复理论与实践

@#ObjectiveTo investigate the intensity of degrading plasma fibrinogen(FIB) and the therapeutic effectiveness of defibrase on treating cerebral ischemia by different administrated ways. MethodsIntraluminal suture method was used to develop reversible middle cerebral artery occlusion (MACO). 154 healthy male Wistar rats were randomized into 2 groups. The rats in intravenous treatment group were injected defibrase intravenously at 0.5,3,6,9,12hours after MACO,while the rats in coeliac treatment group were injected defibrase by abdominocentesis. Meanwhile the control group received normal saline. All rats were killed at 24 hours after MCAO. The thrombus in middle cerebral artery (MCA) and cerebral infarction were examined microscopically in HE stained sections. Infarction volume was measured by using 2,3,5-triphenyltetrazolium chloride staining. 24 rats were selected randomly and injected defibrase by intravenous injection and abdominocentesis. Plasma FIB was measured before and after injection 1,3,6,12,24h by intravenous haemospasia. ResultsPlasma FIB was significantly reduced in intravenous treatment group, and it was lowerest in 3h after intravenous treatment.Clinical Neurological Deficits Scale and infarction volume was significantly reduced in intravenous treatment group than saline control group and coeliac treatment group.There was improvement in Clinical Neurological Deficits Scale in coeliac treatment group compared with that of saline control group, but there was no statistically significant differences at infarction volume.Clinical Neurological Deficits Scale and infarction volume was statistically significant differences in intravenous treatment group at 0.5,3 hours after MCAO. There were no statistically significant differences in intravenous treatment group at 6, 9,12 hours after MCAO.Conclusions Defibrase can reduce the infarction volume in cerebral ischemia early stage.

Experimental study on the therapeutic effectiveness of defibrase in rat focal cerebral ischemia reperfusion model / 中国康复理论与实践

@#ObjectiveTo investigate the therapeutic effectiveness of defibrase in treating penumbra and reperfusion.MethodsIntraluminal suture method was used to develope reversible middle cerebral artery occlusion(MCAO). Rats were subjected to MCAO 3 hours followed by reperfusion for 3, 6, 24, 72 hours, and to MCAO 6 hours followed by reperfusion for 3, 6, 24 hours. The treatment groups rats were injected intravenously defibrase at 0.5 hour before reperfusion. Meanwhile, the control group received normal saline. Clinically Neurological Deficits Scale were evaluated every day. Infarction volume was measured by using 2,3,5-triphenyltetrazolium chloride staining. Pathologic change were examined microscopically in HE stained sections.ResultsThere were significant difference at treatment groups of reperfusion 3 hours after MCAO.Infarction volume and Clinically Neurological Deficits Scale was significant reduced as control group (P<0.05). There were no significant differences at treatment groups of reperfusion 6 hours after MCAO (P>0.05). Cerebral hemorrhage wasn't increased in defibrase treatment group.ConclusionsDefibrase was effective on Clinically Neurological Deficits of rats in reperfusion 3 hours after MCAO.