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OBJECTIVE：To struc turally modify shikimic acid ，and to investigate the reversal effects of its derivatives on paclitaxel-resistant human breast cancer cells MCF- 7/PTX. METHODS ：Using shikimic acid as the lead structure ，1-position carboxyl group was structurally modified to synthesize a series of shikimic acid derivatives through esterification ，amidation， hydrogenation and reduction ，etc. Using non-drug resistant cells MCF- 7 as reference ，MTT assay was used to screen derivatives with inhibitory activity as well as half-inhibitory concentration （IC50）and reversal index （RI）of derivatives to MCF- 7/PTX. With the drug resistance-related transgelin 2 as the target ，the molecular docking of the active derivatives with the drug resistance-related protein was carried out by using Glide 1.0 computer-aided design software. RESULTS ：Totally 15 derivatives were obtained （T1-T15）， of which T 4-T15 were obtained for the first time. MTT assay showed that （3R， 4S， 5R） -N-benzyl-3， 4， 5-trihydroxy-1-cyclohexene-1-formamide（T7），（3R，4S，5R）-N-（3，4，5-trihydroxy-1-cyclohexenylmethyl）-benzylamine（T14）， （3R，4S，5R）-3，4-O-isopropyl-5-O-acetyl-1-cyclohexene-1-methyl formate （T15）inhibited MCF- 7 and MCF- 7/PTX cells to a certain extent ；IC50 values of T 7，T14 and T 15 combined with pacliaxel to MCF- 7/PTX cells were significantly lower than that in negative control （Paclitaxel alone ）group（P＜0.05）. RIs of T 14 and T 15 were higher ，and RIs of the highest dose were 8.8 and 9.3， which were equivalent to positive control verapamil （10.8）. Th e results of molecular docking showed that the hydroxyl groups at positions 3，4 of T 7 could form multiple hydrogen bonds with ； Arg625 and Asp 627 in the catalytic region of transgelin 2. In addition to the hydrogen bond mentioned above at T 7，the mail：batistuta28@126.com secondary amine side chain at position 1 of T 14 could also form hydrogen bond with Glu 657 of transgelin 2. When the hydroxyl group on the T 15 mother nucleus was derived from the donor group ，the binding of the hydroxyl group to transgelin 2 was closer and the inhibition was enhanced. CONCLUSIONS ： The derivatives T 7，T14 and T 15 have certain reverse activity to paclitaxel-resistant human breast cancer cells. The polyhydroxy structure of the mother nucleus is the main structural region of the hydrogen bond between shikimic acid and its derivatives and transgelin 2. The derivation of its power supply group or the introduction of secondary amines and hydrophobic groups into the 1-carboxyl group of shikimic acid is benifit for enhancing the drug resistance reversal effect of derivative .
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Objective To systematically evaluate the performance of the Sysmex CS2000i Automatic Blood Coagulation Analysis System .Methods According to the standards of the Clinical and Laboratory Standards Institute (CLSI) ,the precision ,accuracy ,lin‐earity ,biological reference interval and carry‐over rates of the Sysmex CS2000i Automatic Blood Coagulation Analysis System were detected ,meanwhile the detections of 5 clinical specimens were compared between this system and the Sysmex CA 1500 Automatic Blood Coagulation Analysis System .Results The intra‐assay precision coefficient of variation (CV) ,inter‐day precisions CV carry‐over rate ,accuracy and linearity of plasma prothrombin time ,activated partial thromboplastin time ,fibrinogen and D‐dimmer detec‐ted by the Sysmex CS2000i Automatic Blood Coagulation Analysis System were all consistent with the quality target requirements of our laboratory .Conclusion The Sysmex CS2000i Automatic Blood Coagulation Analysis System has better performance in vari‐ous aspects ,the detection results could be used for the clinical diagnosis and treatment of related diseases .
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Objective To explore the clinical value of combined detection of human epididymis protein 4(HE4) ,carbohydrate an‐tigen 199(CA199) and carbohydrate antigen 125(CA125) in diagnosis of ovarian cancer and benign ovarian cysts .Methods The se‐rum levels of HE4 ,CA125 and CA199 were determined by using chemiluminescent immunoassay in 45 cases of patients with ovarian cancer(ovarian cancer group) ,60 cases of patients with benign ovarian cyst(benign disease group) ,and 30 cases of healthy individu‐al(control group) .Results The serum levels of HE4 ,CA199 and CA125 in the ovarian cancer group were higher than those in the ovarian cancer group and control group ,there were statistically significant differences(P0 .05) .The sensitivity of combined detection of the three indicators increased to 82 .2% ,and the specificity remained at 90 .0% .Conclusion Combined detection of HE4 ,CA125 and CA199 might have clinical significance in early diagnosis and identification of ovarian cancer .
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Objective To evaluate the relevance and accuracy of fibrinogen (Fib) detection by using PT-der assay and Von-Clauss assay on Sysmex CA-1500 Automated Coagulation Analyzer .Methods PT-der assay and Von-Clauss assay on Sysmex CA-1500 Automated Coagulation Analyzer were employed to detect the plasma Fib concentrations of 755 blood samples .The dilution ratios of samples with high Fib concentration were 1∶8 ,2∶7 ,3∶6 ,4∶5 ,5∶4 ,6∶3 ,respectively .The dilution ratios were served as the abscissa ,and the Fib concentrations measured by two methods as the ordinate ,a simple linear regression analysis was per-formed .Results When Fib concentration was in 2 .0- <6 .0 g/L ,the Fib value obtained by Von-Clauss assay was higher than that by PT-der assay(P<0 .01) .When Fib concentration was below 2 .0 g/L or above 6 .0 g/L ,the Fib value obtained by PT-der assay was higher than that by Von-Clauss assay(P<0 .01) .The linear regression equations of PT-der assay and Von-Clauss assay were Y=4 .537 7X+1 .551 3(R2 =0 .897 3) ,Y = 7 .792 2X+ 0 .290 0(R2 =0 .980 5) ,respectively .Conclusion Von-Clauss assay can better reflect the Fib level of human body which has a blood clotting function .
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Objective: To analyze the relevant literature regarding the effect of tuina on postpartum milk secretion and thus summarize the clinical rules on tuina for lactation disorder. Method: Investigate the relationship between tuina and postpartum milk secretion for four aspects, including the initial time of lactation, level of serum prolactin, volume of lactation, and Chinese medicine's understanding of tuina on milk secretion. Result and Conclusion: Tuina on breasts after childbirth can speed and promote lactation. This has been proved by clinical practice over the past hundreds of years, along with modern laboratory and scientific research. This method, therefore, is of great significance in obstetrical nursing.
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Aim To investigate the effects of aloe coarse polysaccharid on proliferation and the intracellular calcium level and the leakage rate of lactate dehydrogen-ase(LDH) of the epidermal cellsin vitro.Methods The epidermal cells were treated with aloe coarse po-lysaccharid of75,150,300,600 and 1 200 mg.L-1respectively.The proliferation of epidermal cells wasobserved interms of the proliferation curve and the pop-ulation doubling/day(PD/d).The concentration ofintracellular calcium and the leakage rate of LDHwerealso measured.Results In aloe coarse polysaccharidgroup,a dose-dependent and statistically significant(P
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Object To study the dynamic growth and reproduction of Hirudinaria manillensis Lesson in laboratory with providing the data of artificially breeding leech in the field. Methods The newly hatched juvenile from same cocoon were bred in 80 cm?60 cm?50 cm aquaria with natural water from rice paddy and weighted every ten days. Water temperature was recorded daily and water was exchanged monthly. Ten chemical elements of water from rice paddy were analyzed in the laboratory. Leeches were allowed to engorge the blood on living rabbits and the amount of engorged blood was measured every time to observe the growth and development, record the copulation and cocoon-deposit, and make the curve of dynamic growth of the leech. Results The newly hatched juvenile grew and developed for 14 months to sexual maturation period by engorging rabbit's blood of five or six times. The leeches were still juvenile in the first three times of engorging, became subadult in the fourth. Then some developed to the sexual maturation period individually in the fifth, and some individually in the sixth. The curve of dynamic growth displayed rising and falling with the record of copulation and cocoon deposit. Conclusion The above study elucidate the dynamic growth, reproduction and the successfully breeding of leeches in the door.
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According to the theory of optimization by ???? ??????????????(俄).this essay propounds two ideal about medical ethics of ethics and the clinic practice.The second involves the optimize methodology including self-study.classroom teaching and case discussion;Via multimedia and network.
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Doctors face relevant ethical responsibilities in the medical process of organ transplantation in China: fair distribution of organs,adaptive judgment of a surgical operation for patients with medium and advanced stage of liver cancer,avoidance of wasting medical resources,and a responsibility to prevent receivers from the risk of contacting HIV and HCV infection.So doctors in China should be provided with relevant ethical and legal knowledge and conceptions to take responsibilities to minimize the above risks and adverse issues,and then keep organ transplantations developing in a moderately healthy style.