Therapeutic oligonucleotides have been one of the hottest areas in R&D of drugs in recent years.The research of analysis method has been widely carried out.Ion-pairing reverse liquid chromatography is the most commonly used method for good resolution and easy docking with MS.A review is presented here on the progress of oligonucleotides analysis with ion-pairing reverse liquid chromatography.The column, mobile phase, MS detection, mechanism of analysis will be discussed.

Human stomach cancer cell line BGC-823 was treated by Tween 80 in combination with hyperthermia 39℃ to 43℃ for 20 to 100 minutes, respectively. The cell ultrastructure and succinate dehydrogenase (SDH) activity were studied at 0 hr, 48hr and 96hr after treatment respectively. Normal human fibroblast was used as control. The main changes of BGC-823 cells induced by hyperthermia were: dilation of endoplasmic reticulum, swelling of mitochondria, increase of fat droplets and decrease in SDH activity. After treatment at 43℃, the mitochondria showed vesicles or myelin figures and the polyribosomes tended to disaggregate. In nuclei, heterochromatin increased and the nucleolus become a dense homogeneous spot or annular ring. A few cells got necrosis. Effects of Tween 80 on BGC-823 cells were similar to that of hyperthermia. When Tween 80 combined with heating, marked synergic action was observed and the damage of membrane structure appeared earlier and more seriously. The effects of 41℃ combined with Tween 80 for 100 minutes were similar to that of 43℃ for 100 minutes alone. The critical temperature of hyperthermia for BGC-823 cells decreased to 41℃. The responses of the human fetal lung fibroblasts were slight and reversible. The results mentioned above suggested that the Tveen 80 enhanced the damage effect of hyperthermia on the tumor cells by decreasing the phase transition temperature of the tumor cells.

Objective To establish the dissolution curves test method of Ribavirin capsules, and investigate dissolution behavior of domestic Ribavirin capsules.To provide experimental basis for generic drugs quality consistency evaluation.Methods According to the first dissolution method (basket method)stated in appendix Ⅹof Chinese Pharmacopeia(2010 edition),the rotation speed was 50 r/min with dissolution medium volume of 900 mL.The dissolution profiles of Ribavirin capsules in four different mediums( pH 1.2 hydrochloric acid solution,pH 4.5 acetic buffer,pH 6.8 phosphate buffer and water) were determined by HPLC.The determination was performed on C18 column with mobile phase consisted of 4 g/L sodium dihydrogen phosphate solution(pH adjusted to 5.0 ±0.05 using 5% sodium hydroxide solution)-acetonitrile(98:2)at the flow rate of 1.0 mL/min.The detection wavelength was 225 nm,and sample size was 10μL.Results The linear range of ribavirin was 2.5-200μg/mL(r=1).RSD of precision and stability tests were lower than 0.5%.The average recoveries were 101.3%, 100.7%, 100.2%, 100.4% in four mediums.Dissolution behavior of capsules can be more consistent and rapid dissolution in pH4.5 and pH6.8 mediums.But they were quite different in pH1.2 and water mediums, and some of their average dissolution at 15 min could not reach 85%.Conclusion This method is accurate and reliable.There is a difference between domestic Ribavirin capsules dissolution behavior, and the formulation processes have room for improvement.

Objective To improve the related substances analysis method of cobamamide.And to further research light degradation characteristics of cobamamide.Methods Determined the related substances of solid and aqueous solution of cobamamide after light degradation by high performance liquid chromatography(HPLC) conditions,which is Merck Hibar C18 column (4.6 mm ×250 mm, 5μm), 0.05 mol/L KH2PO4 solution:acetonitrile (90:10) -80% acetonitrile as mobile by gradient elution and detection wavelength 260 nm.And compared their light stability.The main three kinds of light degradation impurities were determinate from LC-MS.Results Gradient elution made the light degradation impurities separate better.The results of precision and reproducibility tests increased to RSD =0.2% (n=6) and RSD =8% (n=5) from RSD =3.8% (n =6) and RSD=38%(n=5). Cobamamide solution was very sensitive to light, the preparation should be strict dark operation.Two of the light degradation impurities were adenosine and hydroxycobalamin, with the relative response factor 2.5 and 0.7.Conclusion New method is specific, durable and reproducible, which can be used for quality control of cobamamide.

Objective To analyze peroxide value and anisidine value of ethyl polyenoate soft capsules and imported drugs and evaluate the oxidative stability.Methods The analysis was carried out on a TSK gel ODS-100 V(250 mm ×4.6 mm,5μm)with methanol-water(98:2,V/V)as the mobile phase to determine the structure of the vitamin E as antioxidant.The influence on the antioxidation effect of tocopherol acetate andα-tocopherol as excipient in omega-3 polyunsaturated fatty acid ethyl ester drugs was evaluated.Results The structure of vitamin E as antioxidant in domestic drugs was acetate, while vitamin E as excipient in foreign drugs had the structure of α-tocopherol monomer.As antioxidant, the antioxidation effect of tocopherol acetate was better thanα-tocopherol.The structure of vitamin E had a direct impact on the antioxidation effect of omega-3 polyunsaturated fatty acid ethyl ester drugs.Conclusion The studies provide the basis for evaluate rationality of antioxidant in ethyl polyenoate soft capsules scientifically, which has positive significance for controlling the quality of the drug effectively.

OBJECTIVE： To establish performance management system that can effectively guide the realization of pharmacist value. METHODS： Using action learning method， through continuous questioning， reflection and execution to establish a step-by-step and in-depth pharmacist performance management system in our hospital. The effects of performance management system were evaluated with outpatient service satisfaction and the times of pharmacist consultation. RESULTS： From 2013 to 2018， the performance management system was established， involving team performance （taking the results of team quality control inspection at the end of the month and the monthly work report of team leaders as indicators）/personal performance （taking pharmacist’s performance， work attitude and ability as indicators）/post competency （change of assessment indicators with the position of pharmacist， examination of clinical pharmacists drug counseling， etc） 3 levels. The establishment of performance management improved team enthusiasm and service satisfaction， optimized the talent structure， enlarged the professional ability and influence of pharmacists， and improved the income structure of pharmacists. Compared with 2013， outpatient service satisfaction increased from 88％ to 95％ in 2018. Compared with 2016， the times of pharmacist consultation increased from 30 to 92 in 2018. Pharmacists could increase their income by providing pharmaceutical services to clinical departments. CONCLUSIONS： The established pharmacist performance management system can effectively improve the enthusiasm of pharmacists and promote the work of pharmacists.

Objective To investigate the effect of chronic and unpredictable pre-gestational stress on the serum cortisol level of the offspring,as well as the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB) in hippocampus when they were 2 month old.Methods Adult female SD rats were divided randomly into 2 groups:the control group and the chronic unpredictable stress (CUS) model group.All rats were tested in the open field test and sucrose intake test before and after CUS protocol.All offspring rats were sacrificed when 2-month old.Serum cortisol (COR) levels were determined by using a standard radioimmunoassay kit.The expressions of BDNF and TrkB in hippocampus were studied by immunoreactivity quantitative analysis.Results 1.After CUS procedure,CUS group showed decreasing activities in the open field test and decreasing sucrose consumption in sucrose intake test compared to the control group and before CUS procedure.2.The serum COR levels in the female offspring rats of CUS group (128.9 ± 7.3) μg/L were higher than those of the control group (119.9 ± 9.0) μg/L,as well as the male offspring of CUS group(116.5 ± 10.9) μg/L compared with the control group(105.4 ± 10.4) μg/L,but the body weight and brain weight between the offspring of 2 groups were not statistic significance.3.Immunoreactivity quantitative analysis showed that the gray values of BDNF in the female offspring of CUS group (36.1 ± 8.5) decreased compared with the control group(42.4 ± 6.9),as well as the male offspring of CUS(39.6 ± 8.4)compared with the control group (43.7 ± 6.4).4.The gray values of TrkB in the female offspring of CUS group (47.1 ± 2.9) decreased than the control group(50.2 ± 3.9),as well as the male offspring of CUS (46.5 ± 6.7)compared with control group(50.5 ± 5.4).Conclusion Pre-gestational stress reduced the expressions of BDNF and TrkB in hippocampus of the offspring which may relate to hypothalamic pituitary adrenal.

The role and function of nurses in the application of assisted reproductive technology were sorted out.Addressing potential ethical dilemmas,this paper analyzed the restrictive factors in dealing with difficulties in nursing practice and proposed the construction of a nursing ethics literacy system.It is suggested to improve ethical rules and education systems,strengthen case education,enhance risk prevention capabilities,and cultivate a healthy ethical culture,so as to effectively enhance nurses'ethical literacy.

OBJECTIVE:To investigate the effects and safety of gamma globulin combined with phototherapy on serum preal-bumin(PAB)and total bile acid(TBA)of ABO hemolytic children. METHODS:A total of 90 ABO hemolytic children in our hos-pital during Feb. 2014-Sept. 2016 were selected as research objects and divided into observation group and control group according to random number table,with 45 cases in each group. Both groups were given routine active correction of hypoxia and pretreatment for possible hypoglycemia and hypothermia. Control group was additionally given phototherapy with wavelength of 425-475 nm. Ob-servation group was additionally given Human immunoglobulin for intravenous injection (pH4) 1.0g/kg was added to normal saline 10 mL,ivgtt,on the basis of control group and treated for 1 d. The time of jaundice regression,phototherapy duration and hospital-ization time were compared between 2 groups,and the levels of PAB and TBA were compared before and after treatment. The occur-rence of ADR was recorded in 2 groups. RESULTS:The time of jaundice regression,phototherapy duration and hospitalization time in observation group were significantly shorter than control group,with statistical significance(P<0.05). Before treatment,there was no statistical significance in the levels of PAB or TBA between 2 groups(P>0.05). After treatment,the level of PAB was increased significantly in 2 groups,while the level of TBA was decreased significantly;the observation group was significantly better than the control group,with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Gamma globulin combined with phototherapy can significantly shorten the time of clinical symptom im-provement,increase serum level of PAB whlie decrease serum level of TBA in ABO hemolytic children,with good safety.

Objective:To study the correlation between OPRM1 A118G gene polymorphism (rs1799971) and the dosage of opioid analgesics in patients after lumbar decompression.Methods:From July 2017 to September 2018, 147 patients undergoing selective posterior lumbar decompression under general anesthesia in the People's Hospital of Xinjiang Uygur Autonomous Region were treated with sufentanil intravenous controlled analgesia(PCIA). The gene polymorphism was detected by PCR.The VAS, Ramasy sedation score, total dosage of sufentanil and adverse reactions of sufentanil in 48 h after operation were observed.Results:The genotype frequencies of AA, GA and GG were 30.6%, 55.5% and 13.9%, respectively, the difference was statistically significant(χ 2=6.324, P=0.423), and G and A allele frequencies were 41.7%, 58.3%, respectively, the difference was statistically significant(χ 2=5.559, P=0.184). There were no statistically significant differences in SpO 2, Ramasay sedation score and VAS score among the groups after operation(all P>0.05). The total dosage of sufentanil in OPRM1 mutant GG[(151.0±23.4)μg] and GA[(132.0±19.1)μg] was higher than that in AA[(123.0±16.2)μg] within 48 h of PCIA, the differences were statistically significant( t=5.206, 2.817, all P<0.05). Conclusion:The OPRM1 A118G gene polymorphism(rs1799971) is correlated with the dosage of opioid analgesics after lumbar decompression.