AIM: To discuss the protective effects and possible mechanisms of 17β-estradiol on human retinal pigment epithelial ( RPE) cells induced by high glucose. ·METHODS: RPE cells were cultured and divided into four groups according to randomized controlled method:blank control group:the cells were treated with 5. 5mmol/L routine glucose medium for processing; high glucose group: cells were treated with 100mmol/L glucose for 12h;17β-estradiol low concentration group: after treated with 10 μmol/L 17β-estradiol, cells were treated with 100mmol/L glucose for 12h; 17β-estradiol high concentration group: after treated with 100 μmol/L 17β-estradiol, cells were treated with 100mmol/L glucose for 12h. Cell viability were tested by MTT colorimetric detection. Cells apoptosis were detected by Hochest33258 staining. Intracellular reactive oxygen species( ROS) level were detected by H2 DCFDA staining. Expression of CAT, SOD and MDA were tested by colorimetric detection. · RESULTS: RPE cell activity decreased with the concentration of glucose increased; 17β-estradiol inhibited high glucose-induced cell viability decrease in RPE cells, decreased the apoptosis rate of RPE cells and intracellular ROS generation; besides, 17β-estradiol significantly increased the expression of CAT, SOD and decreased the expression of MDA in RPE cells. ·CONCLUSION: The 17β-estradiol effectively inhibited high glucose -induced RPE cells damage, which provide reliable experimental basis for the treatment of injuries in RPE cells.

Objective To investigate the plan quality between two treatment planning systems (TPSs) for volumetric modulated arc therapy (VMAT). Methods VMAT plans based on Varian Eclipse and Philips Pinnacle TPS were designed for 10 cervical cancer patients (2, 3 Arcs) and 10 prostate cancer patients ( 1, 2 Arcs) . The delivery system of VMAT was Varian ClinaciX machine, and RapidArc was used. The treatment plan quality between the two TPSs was evaluated based on dose distribution, delivery efficiency, and parameter settings. The differences between the two TPSs were compared using paired t-test. Results For cervical cancer patients, the 2-Arc VMAT plans based on the Pinnacle was slightly better than those based on the Eclipse in terms of the conformal index ( CI) of planning target volume ( PTV) , rectum V30 and V40 , and bladder V30 and V40 , and the homogeneity index ( HI) of PTV and PTV1 as well as CI of PTV1 in the Eclips were slightly better than those in the Pinnacle( P<005) Pinnacle were slightly worse than those in the Eclipse ( P>005) . The number of monitor units with 2-Arcs and 3-Arcs plans of the Eclipse was significantly smaller than those in the Pinnacle (P<005). For prostate cancer patients, The 1-arc VMAT plans of the Pinnacle TPS were slightly superior to those of the Eclipse TPS in terms of the HI of PTV, rectumV30 and V40 , and bladderV30 and V40 , but the former was slight inferior to the latter in terms of the CI of PTV (P<005). The number of monitor units of 1-arc and 2-Arcs plans showed no significant difference between the two TPSs (P>005). Conclusions For patients with cervical cancer and prostate cancer, the VMAT plans based on Varian Eclipse and Philips Pinnacle TPS can achieve a clinically acceptable dose distribution and show a little difference in the treatment plan quality. However, we will still need more cases to further study and determine the performance characteristics of the commercial TPSs for optimizing VMAT.

OBJECTIVETo study the chemical constituents of Ervatamia hainanensis.

METHODThe compounds were separated and purified by column chromatography with silica gel, and identified by IR, MS, NMR and 2D-NMR.

RESULTFive compounds were identified as I (isolariciresinol 9-O-beta-D-glucopyranoside), II (cycloartenol), III (beta-amyrin acetate), IV (beta-sitosterol), V (daucosterol), respectively.

CONCLUSIONAll the compounds were isolated from this plant for the first time.

Apocynaceae ; chemistry ; Glucosides ; chemistry ; isolation & purification ; Oleanolic Acid ; analogs & derivatives ; chemistry ; isolation & purification ; Phytosterols ; chemistry ; isolation & purification ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Sitosterols ; chemistry ; isolation & purification ; Triterpenes

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Objective To observe the changes of circadian characteristics and stress-response-related physiological parameters including respiration, blood pressure, electrocardiography and body temperature of conscious rhesus monkeys by implantable telemetry technique. Methods Surgery was performed on 8 rhesus monkeys (half male and half female, 3-5 years old) for implantation of a telemetry transmitter. After 3 weeks of recovery, the physiological parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus monkeys without binding were automatically recorded by a DSI telemetry system and the data were analyzed by the Ponemah software. Results Some electrocardiographic indexes showed significant differences at daytime and nighttime (P＜ 0. 05 or P＜ 0. 01) including mean heart rate (HR) ( 155. 0-122. 4 times/min), respiratory rate interval (RR-I) (410. 8-535. 7 ms), T-wave amplitude (T-A) (0. 181-0. 157 mV), PR interval (PR-I) (80. 4-87. 4 ms), QT interval (QT-I) (224. 8-263. 9 ms), and corrected QTcb interval (QTcb) (352. 3-366. 7 ms). The indexes of blood pressure and respiration at daytime were significantly higher than those at nighttime (P＜ 0. 01), including the mean systolic pressure (SYS) at daytime and nighttime (144. 6-131. 6 mmHg), diastolic pressure (DIA) (99. 8- 89. 9 mmHg), mean arterial pressure (MAP) (121. 5-110. 2 mmHg), tidal volume (TV) (64. 5-36. 6 mL), minute ventilation (MV) (1931. 9-920. 1 mL/min), and respiratory rate (RR) (32. 3-25. 4 times/min). Cleaning and feeding activities of the laboratory staff at 9: 00 a.m. and 2: 00 p.m. had a certain effect on the stress-responses in the monkeys. Conclusions The parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus macaques observed by implanted telemetry system show obvious circadian changes, which can truly reflect the changes of physiological indexes at daytime and nighttime, and avoid the stress in hungry monkeys caused by the feeding and cleaning activities of laboratory staff. This technique can improve the efficiency of drug safety pharmacology studies, reduce the number of animals used and meet the requirements of 3R principles.

Objective To evaluate the sensitivity to 5 clinically commonly used anticancer drugs in vivo using the zebrafish xenotransplantation models of human lung cancer,stomach cancer,and liver cancer cells,respectively. Methods Zebrafish xenotransplantation models of A549 lung cancer cells,SGC-7901 stomach cancer cells and HepG2 liver cancer cells were established. The xenograft models of A549 cells were treated with three different doses of cis-platinum, paclitaxel, vinorelbine, endostar and bevacizumab, respectively. The SGC-7901 model was treated with three concentrations or doses of paclitaxel, irinotecan, hydroxyurea, cis-platinum and 5-fluorouracil, respectively. And the HepG2 model was treated with three concentrations or doses of adriamycin,gemcitabine,hydroxyurea,cis-platinum and 5-fluorouracil. The tumors were analyzed and quantified in vivo by fluorescence microscopy,and the inhibition rates of tumor growth with each drug were calculated and compared with the model control group for statistical significance. Results All of the tested anticancer drugs showed inhibitory effect on tumor cells in the zebrafish xenograft models with statistical significance in a dose-dependent manner. During the drug sensitivity test,the inhibition rate of bevacizumab on A549 lung cancer cells decreased in the order(65%)> cis-platinum(55%)> vinorelbine(40%)> endostar(39%)>paclitaxel(27%). As for the SGC-7901 stomach cancer cells, the tumor growth inhibition rate decreased in the order hydroxyurea(46%)> 5-FU(31%)= irinotecan(31%)> paclitaxel(26%)> cis-platinum(24%). And the therapeutic effect of cis-platinum on the HepG2 liver cancer cells decreased in the order(64%)> hydroxyurea(56%)>gemcitabine(46%)> adriamycin(45%)> 5-FU(38%). Conclusions Zebrafish xenotransplantation models of cancer cells are suitable for in vivo sensitivity test of anticancer drugs.

China ; Early Detection of Cancer ; Fluorodeoxyglucose F18 ; Humans ; Neoplasms/diagnostic imaging* ; Physical Examination ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Radiopharmaceuticals ; Sensitivity and Specificity

Objective To study the correlation between coronary artery stenosis and endothelial dysfunction in patients with coronary heart disease and subclinical hypothyroidism.Methods According to the results of coronary angiography and thyroid function,the patients were divided into coronary heart disease with subclinical hypothyroidism (group A,n=71),coronary heart disease without subclinical hypothyroidism (group B,n=73), and normal coronary angiography (control group,n=59).The degree of coronary artery stenosis was evaluated by Gensini integral method.Fasting blood was taken to measure nitric oxide (NO),high sensitivity C reactive protein (hs-CRP),and endothelin (ET)to evaluate endothelial dysfunction.Results TC,TG,LDL-c,FT3,TSH,hs-CRP,ET and Gensini score were higher in Group A than in Group B and control group (P＜0.05).The level of NO in Group A and Group B were lower than that in control group (P＜0 .0 5).Multivariate Logistic regression analysis showed that age,TSH,ET and NO were independent risk factors for coronary heart disease.ET and NO levels in patients with coronary heart disease combined with subclinical hypothyroidism were correlated with Gensini scores (r=0.431,r=-0.383,P＜0.001).Conclusion Subclinical hypothyroidism may cause endothelial dysfunction in patients with coronary heart disease,which may increase cardiovascular risk in these patients.

Objective: To investigate the mechanism of Zuoguiwan in treating ovariectomy-induced osteoporosis rats by receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway mediated by β₂-adrenergic receptor (β₂AR). Method: Forty Sprague-Dawley female rats were randomly divided into Sham-operated group (Sham) and four ovariectomized (OVX) subgroups. Rats in Sham and OVX groups were treated with 17β-estradiol (50 μg·kg^-1·d^-1), and low and high-dose ZGW (2.3,4.6 g·kg^-1 lyophilized powder) for 3 months, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum markers of bone turnover. Micro-CT was used to evaluate and measure trabecular bone microarchitecture and bone mineral density (BMD) of the right distal femur. Western blot analysis and Real-time PCR were used to measure mRNA and protein expressions of β₂AR, OPG and RANKL. Result: After 12 weeks of treatment with Zuoguiwan, the level of serum β-cross-linked c-telopeptide of type Ι collagen (β-CTX) (P<0.01) was lower, while the level of serum bone-specific alkaline phosphatase (BALP) was higher (P<0.01) than those in the OVX group. Moreover, it could prevent the OVX-induced bone loss, and alleviate the trabecular bone microarchitecture of distal femur. Furthermore, Zuoguiwan could up-regulate the mRNA and protein expressions of OPG in tibia of the Zuoguiwan groups(P<0.01), reduce the mRNA and protein expressions of β₂AR in the hypothalamus (P<0.01), and down-regulated the mRNA and protein expressions of RANKL (P<0.05) in the tibia, compared with those in the OVX group. Conclusion: The mechanism of Zuoguiwan in alleviating BMD and trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats might be related to the regulation of RANKL/OPG Pathway mediated by β₂AR.

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.