Although small molecule drugs (SMD) are still mainstream for the treatment of diseases, large molecule biologicss of many advantages, pose a challenge to the further discovery and use of SMD. The advantages of SMD are the convenience of oral administration and good patient compliance. However, the challenge with SMD is to integrate the PD, PK, selectivity and safety into a chemical structure. Because of their small size and surface area they often bind to various proteins, and off-target actions can cause adverse reactions. In this sense, selectivity is critical. Based upon target as the core to construct a chemical structure, it is necessary to consider the requirements of all the attributes, but achievement of the full-dimensional optimization is difficult. Modern drug discovery has been greatly enhanced by molecular biology and structural biology, and new strategies and technologies have emerged, which have created many successful medicines. For example, under the guidance of structural biology, covalent binding drugs connect moderate "electrophilic warheads" to the appropriate positions of molecules, and upon binding to their targets the electrophiles are irreversibly linked to the target by covalent bonds. Molecular biology can be directly applied to the development of antibody-coupled drugs (ADC). The antibody (A) acts as a carrier and a guide (for PK), and carries toxic molecules (D) into cancer cells, thus playing a killing role (for PD). The separate pharmacodynamic and pharmacokinetic entities are coupled (C) by linkers. PROTACs are also bifunctional molecules, which recruit a target protein and ubiquitin ligase E3 to form a ternary complex, which then acts as a catalyst to ubiquitinate the target protein and lead to degradation by the proteasome. In addition, in recent years, the combination of two fixed-dose drugs has improved selectivity, safety, and long-term benefit with many severe diseases, and can be regarded as an innovative strategy of physical combination. This review discusses some successful examples to briefly present the principles from the perspective of medicinal chemistry and therapeutic application.

OBJECTIVE:To provide a simple and reliable method to estimate confidence intervals of incremental cost-effectiveness ratios for pharmacoeconomics evaluation in China. METHODS:Through retrieving relevant foreign literature,the idea and mathematical properties of non-parametric Bootstrap method were described and the method for calculating confidence intervals were explained by giving an example. RESULTS&CONCLUSION:Non-parametric Bootstrap method is simple and reliable for the calculation of confidence intervals of pharmacoeconomics. When the distribution of samples is skewed significantly or the sample size is not plenty enough,we still need to be cautious to adopt non-parametric Bootstrap method.

Adult ; Cross-Sectional Studies ; Female ; Humans ; Job Satisfaction ; Nurses ; Ophthalmology ; manpower ; Stress, Psychological ; Surveys and Questionnaires ; Workload ; Young Adult

Objective To study paraquat adsorbability of different field soils in Guangxi province of China. Methods HPLC method was adopted to measure the peak area of paraquat in three different media of four types of soils. Chromatographic column was Kromasil C18 column (4. 6 mm×200 mm, 5 μm); mobile phase was acetonitrile-water (including 0. 03 mol·L-1 sodium heptanesulfonate and 0. 24 mol·L-1 phosphoric acid) at a ratio of 397 (pH adjusted to 2. 0 by triethylamine). Detection wave length was 258 nm; column temperature was 25 ℃; the injection volume was 20 μL; flow rate was 0. 8 mL·min-1 . The peak areas of paraquat before and after being adsorbed were compared to calculate the adsorption rate of paraquat in different soils. Results All tested soil samples possessed the adsorption rate of paraquat over 99. 0%. Conclusion Four common field soils in Guangxi province can be used as temporary effective absorbents for the first-aid of paraquat poisoning.

In order to explore the clinical application and mechanism of the ghost points in the treatment of mental diseases, taking "the ghost points" and "mental diseases" as the theme and the key words, the literatures in recent 10 years on the treatment of mental diseases with the ghost points were collected from CNKI and Wanfang database and analyzed. It is discovered that the ghost points can treat schizophrenia, manic-depressive disorder, dementia, stroke, loss of consciousness, insomnia. anxiety, depression and hysteria and the efficacy is favorable. It is believed that the ghost points act on balancing yin and yang, regulating qi and blood, regaining consciousness and tranquilizing the mind and they achieve the very excellent effect on mental diseases. At present, the reports on this aspect are limited. Hence, it is required to promote the study on the clinical application and mechanism of the ghost points so as to enlarge the clinical indications of the ghost points and provide the powerful support on mechanism for the treatment of mental diseases.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Mental Disorders ; therapy

Objective To investigate the changes of serum immunoglobulin E(IgE)?T cell subgroups and cytokines in asthmatic children and to provide theoretical basis for the management of asthmatic children.Methods T cell subgroups were determined by indirect immuofluorence method mono clone antibody, the detection of IgE,interleukin(IL) 4,IL 6,IL 8,interferon ?(IFN ?) were done by ELISA method, and 20 normal children were served as control group.Results There were significant differences of CD3 +,CD4 +,CD4 +/CD8 + among the stages of exacerbation and convalescence of asthmatic children and control group.( P0.05).In the stage of convalescence the levels of IL 2,IFN ? were lower than control group( P0.05).Conclusions Allergic asthmatic patients between the exacerbation and convalescence stages still had immunologic imbalance,indicating increased number of CD4 +T cell(mainly Th2 cells)and hyperfunction;the insufficient number and(or) the inactivity of CD8 +T cell may induce immunological disturbance ,which is the major mechanism of asthmatic attacks. These findings suggest the patients in an abnormal immunological state should receive continuous anti allergic therapy.

Objective To investigate the effects of levosimendan on percutaneous coronary intervention ( PCI) in patients with ischemic heart failure. Methods From January 2013 to June 2016,eighty patients with ischemic heart failure undergoing coronary intervention in Pingdingshan People′s Hospital No. 1 were randomly divided into treatment group ( 40 cases) and control group ( 40 cases) . The treatment group was treated with levosimendan on the basis of routine medicine 2 days before operation,and the control group was given routine medication before operation. The baseline clinical data, operative success rate, complications, left ventricular ejection fraction ( LVEF%) after 1 month, 6 min walking distance, plasma brain natriuretic peptide ( BNP ) , creatinine and other cardiac and renal functions were observed and compared between the two groups. Results The differences of the baseline clinical characteristics including age (65. 5±3. 9 vs. 63. 9±3. 6),male (26 cases (65. 0%) vs. 23 cases (57. 5%) ),hypertension (21 cases (52. 5%) vs. 19 cases (47. 5%) ),diabetes (17 cases ( 42. 5%) vs. 14 cases ( 35. 0%) ) , hyperlipidaemia ( 30 cases ( 75. 0%) vs. 29 cases ( 72. 5%) ) , smoking (21 cases (52. 5%) vs. 19 cases (47. 5%) ),COPD (7 cases (17. 5%) vs. 6 cases (15. 0)%), LDL?C ( (4. 5±1. 0) mmol/L vs. (4. 4±1. 1) mmol/L),BMI ( (25. 9±3. 3) vs. (25. 6±3. 5) ) were not significant (t/χ2=1. 30,0. 47,0. 20,0. 47,0. 07,0. 20,0. 09,0. 49,0. 39,P=0. 20,0. 49,0. 66,0. 49,0. 80, 0. 66,0. 76, 0. 63, 0. 70 ) . There was no significant difference in coronary artery lesion between two groups, including single vessel lesion (11 cases (27. 5%) vs. 15 cases (37. 5%) ),double vessel lesion ( (22 cases ( 55. 0%) vs. 19 cases ( 47. 5%) ) ,three vessel lesion ( ( 7 cases ( 17. 5%) vs. 6 cases ( 15. 0%) ) and left main coronary artery disease (7 cases (17. 5%) vs. 6 cases (15. 0%) ) (Z=-0. 88,P=0. 38). The time of percutaneous coronary intervention ( ( 51. 0±8. 6) min vs. (49. 6 ±9. 6) min),the time of X?ray exposure ( (20. 3±7. 0) min vs. (18. 4±5. 6) min),material consumption ( (123. 2±16. 6) ml vs. (117. 3±25. 1) ml) between two groups have no difference ( t/χ2=0. 70,1. 39,1. 24,P=0. 49,0. 17,0. 22) . There were significant differences between the two groups in the success rate of operation ( 38 cases ( 95. 0%) vs. 31cases ( 77. 5%) , heart failure ( 1 cases ( 2. 5%) vs. 6cases ( 15. 0%) ) and complications ( 2 cases ( 5. 0%) vs. 11 cases (27. 5%) ) (χ2=5. 17,3. 91,7. 44,P=0. 02,<0. 05,<0. 01). Compared with the control group,the treatment group had greater advancement in LVEF,6 min walking distance,BNP and creatinine level at one month after operation ( F=6. 10,63. 60,51. 00,348. 00,P=0. 02,<0. 01,<0. 01,<0. 01) . Conclusion Levosimendan can effectively improve the heart function and renal function, improve the success rate of PCI in patients with ischemic heart failure and reduce the incidence of complications.

ObjectiveTo observe the effect of acupuncture at the ghost points on anxiety and depression in methamphetamine (MA)-dependent subjects.MethodSixty MA-dependent males were randomized into a control group, acupuncture groupⅠand acupuncture groupⅡ. The control group didn’t receive any intervention; inacupuncture groupⅠ, bilateral Neiguan (PC6), Shenmen (HT7), Sanyinjiao (SP6), and Jiaji points (EX-B2) were selected; Shuigou (GV26), Shangxing (GV23), Chengjiang (CV24), and bilateral Daling (PC7), Jianshi (PC5), Shenmai (BL62), and Quchi (LI11) were selected in acupuncture groupⅡ. For the three groups, treatment was given three times a week, totally for 12 times. The Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were observed before treatment, and respectively after 1, 2, 3, and 4-week treatment.ResultAfter the first-week treatment, the HAMA and HAMD scores in acupuncture groupⅡwere significantly lower than that in the control group (P<0.05);afterthe second, third, and fourth week, the HAMA and HAMD scores in acupuncture groupⅠandⅡwere significantly lower than that in the control group (P<0.05); after the second and third week, the HAMD score in acupuncture groupⅡwas significantly lower thanthat in acupuncture groupⅠ(P<0.05). However, after 4-week treatment, there was no significant difference in comparing the HAMD score between the two acupuncture groups (P>0.05).ConclusionAcupuncture at the ghost points and at the effective points selected according to previous studies both can improve anxiety and depression state in MA-dependent subjects, but acupuncture at the ghost points can possibly produce a more significant effect in improving depression state in MA-dependent subjects in the midway of the treatment.

Objective To investigate the effect and safety of Guard wire technology in percutaneous coronary intervention( PCI) of ostial lesions and the treatment of passing ostial lesions. Methods Thirty?five cases patients needing PCI of ostial lesions were selected and divide randomly in to A group(n=18) and B group(n=17) . A group used Guard wire technology and B group used common method. The X?ray exposure time,complications,the amount of contrast agents of two groups were analyzed. Forty?six cases patients needing the treatment of passing ostial lesions were divided randomly into C group( n=25) and D group( n=21) . C group used Guard wire technology and D group used common method. Complications of two groups were investigated. Results The X?ray exposure time, the amount of contrast agents and complications of A group were fewer than that of B group,the difference were significant((5. 7±0. 6) min vs. (9. 3±1. 1) min,(84. 3 ±6. 4) ml vs. (94. 1±10. 0) ml,6%(1/18) vs. 35%(6/17);t or χ2=-11. 80,-3. 50,4. 80;P<0. 05). The complications of C group was lower than that of D group,and the difference was significant( 4%( 1/25) vs. 29%( 6/21);χ2=5. 30,P<0. 05) . Conclusion Guard wire technology is safe and useful in percutaneous coronary intervention of ostial lesions and the treatment of passing ostial lesions,and it is feasible in clinical practice.

[Summary] This paper was to investigate whether serum angiopoietin-like protein 2 (Angptl 2) is associated with macrovascular complications in type 2 diabetes mellitus.The results showed that there were statistically significant differences in serum Angptl 2 levels among control group and groups of type 2 diabetic patients with or without carotid atherosclerosis [0.98 (0.82-1.22),3.70 (2.69-4.85),1.17 (0.76-2.47) ng/ml].Logistic regression showed that Angptl 2 was an independent risk factor of macrovascular complications in the patients with type 2 diabetes.