The quality control of new drug cilnical trial is the effective guaranty for the pharmaceutical safety and effective after available on market. Enhancing the inspection and quality control of new drug clinical trials provide the crucial importance to achieve a persistent profitable standard. This paper mainly discussed the problems of current clinical trials based on annual check of drug clinical trial institution.
Clinical Trials as Topic ; Drug Evaluation ; Health Facilities ; Humans ; Quality Assurance, Health Care ; Quality Control

Background Intravitreal injection of triamcinolone acetonide (TA) can effectively eliminate central vein occlusion macular edema and improve visual acuity, and photopic negative response (PhNR) can reflect the inner retinal function of RGCs and their axons. It is possible there is a correlation between these two observations.Objective This study was to evaluate the changes of PhNR of flash electroretinogram (F-ERG) after intravitreal injection of TA for macular edema in central retinal vein occlusion ( CRVO ). Methods Thirteen eyes of 12 patients with macular edema caused by CRVO received an injection of 0. 1 ml (4 rg) of TA. PhNR,visual acuity and retinal thickness of macular area were assessed with Roland RETI scan 3. 15 system,decimal visual chart and Stratus optical coherence tomography (OCT) before and 4 weeks after the administration of TA. Written informed consent was obtained from each subject before any medical procedure. Results Visual acuity was improved in 12 eyes and stable in 1 eye 4 weeks following the intravitreal injection of TA. OCT showed that the retinal thickness of the macular area was reduced ;meanwhile,elevation of the amplitude of PhNR also was seen in the F-ERG after the administration of TA in comparison with before the administration of TA. The calculated results determined that the visual acuities were 0. 32t0. 12 and 0. 48±0. 09 (t=6. 325 ,P=0. 000) ,and the retinal thickness values of the macular area were (459.46± 131.31 ) μm and ( 297.54 ±43.31 ) μm ( t = 5.961, P = 0. 000 ), and the average amplitude of PhNR were ( 80. 23±22.96 ) μV and (61.28 ±20. 16 ) μV ( t = 4. 438, P = 0. 001 ) before and after the intravitreal injection of TA, respectively,showing significant differences. No significant correlation was found between PhNR amplitude and retinal thickness of the macular area both before and after the administration of TA ( before: r = 0. 587, P = 0. 035; after:r=-0. 011 ,P = 0. 971 ). Conclusion PhNR can be used for evaluating the status of inner retina after intravitreal injection of TA for macular edema of CRVO.

The rate of corneal graft rejection is still high for high-risk keratoplasty although immune suppression drug is routinely used.The role of traditional Chinese medicine in corneal transplantation is concerned gradually.Heijingpaichitang on the prevention and treatment of rats with high-risk corneal allograft rejection needs further study.Objective This study was to investigate the inhibitory effect of heijingpaichitang on high-risk corneal transplantation immune rejection in rats.Methods Sixteen female SD rats were used as the donors and 32female Wistar rats were served as recipients.The high-risk corneal trasplantation models were established by corneal suture in 32 Wistar rats,and then homogeneity variant SD-Wistar corneal transplantation was performed.The recipients were randomized into model control group,cyclosporinc A (CsA)group,heijingpaichitang group and CsA +heijingpaichitang group.CsA,heijingpaichitang and CsA + heijingpaichitang was orally administered 4 days after operation once per day for 15 days,and normal saline solution was used at the same way in the model control group.Ocular anterior segment reaction was examined under the slit lamp and corneal opacification,edema and neovasculation were scored based on Larkin' s criteria.Rejection index of the corneal graft was recorded and the graft survival time was calculated.The pathological examination of the corneal graft was carried out in all rats,and the inflammatory cells in the corneas and CD4+ cells in the periphery blood were assayed using flow cytometry.The use of the animals complied with ARVO Statement.Results Corneal graft rejection occurred in 10 days after operation in the model control group,12-13 days in the CsA group and heijingpaichitang group and 22 days in the CsA +heijingpaichitang group.Compared with model control group,the scores of the corneal opacification,corneal edema and neovascularization were significantly lower in the CsA group,heijingpaichitang group and CsA+heijingpaichitang group (P＜0.05),and all the scores were declined in the CsA+ heijingpaichitang group compared with CsA group and heijingpaichitang group(P＜0.01),but no significant differences were seen in the scores between the CsA group and heijingpaichitang group(P＞0.05).The mean survival time of grafts was (10.38 ±1.69)days in the model control group,(22.50 ± 3.07) days in the CsA + heijingpaichitang group,with the significant difference (t =-9.790,P =0.000).The pathological examination of graft showed that the lymphocytes and new blood vessels were less in the CsA+heijingpaichitang group compared with CsA group and heijingpaichitang group 15 days after operation.Flow cytometry verified that the number of lymphocytes in graft,CD4+cells and CD4+/CD8+ in periphery blood were significantly lower in the heijingpaichitang group,CsA group and CsA+heijingpaichitang group compared with model control group (P＜0.05).Conclusions Heijingpaichitang can inhibit immune rejection to certain extent in high-risk corneal transplantation rat and has a similar effect to 0.1％ CsA.Heijingpaichitang and 0.1％ CsA have a synergistic effect.

Objective To study the effect of lidocaine on the expression of CD11b/CD18 and MPO in lung injury after hemorrhagic shock in rats. Methods Eighty male Wistar rats weighing 230-270 g were randomly divided into 4 groups: sham operation group ( group Ⅰ, n = 8 ) received operation without shock, shock group ( group Ⅱ, n = 8 ) received hemorrhagic shock without resuscitation , normal saline treatment group (group Ⅲ, n = 32 ) received normal saline after shock, lidocaine treatment group ( group Ⅳ, n = 32 ) received lidocaine after shock. The animals were anesthetized with intraperitoneal pentobarbital sodium 40 mg? kg-1 . Hemorrhagic shock was induced by withdrawing blood from right femoral artery at the rate of 2.0 ml?kg-1? min-1 , MAP was maintained at 40 mm Hg for 60 min before resuscitation. Direct arterial MAP and HR were continuously monitored. Group Ⅳwas received lidoacaine at the beginning of resuscitation with a bonus dose 2.0 mg? kg-1 and then followed continuous infusion1.0mg?kg-1?h-1 for 2 h. Group III was received the same dose of normal saline. Flow cytometric analysis was used to assess the expression of CD11b/CD18 on leukocyte and the change of myeloperoxidase (MPO) in the lung was studied at the end of shock (groupⅡ ) and at 2,4, 8, 12 h after resuscitation (group Ⅲ, group Ⅳ) . The rats were sacrificed and the piece of lung was immediately removed for electron microscopic examination. Result In group Ⅲand group Ⅳ ,the expression of CD11b/CD18 on PMNs and MPO in lung were increased significantly compared with Group Ⅰ. Microscopic examination indicated the longer time of reperfusion ,the more serious injury of the lung. And in groupⅣ ,the changes of CD11b/CD18 and MPO were reduced as compared with group Ⅲ (P

Background: Myocardial infarction (MI) is a major disease burden. Wild?type p53?induced phosphatase 1 (Wip1) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wip1 in cardiac adaptation to MI is unknown. We investigated the significance of Wip1 in a mouse model of MI. Methods:The study began in June 2014 and was completed in July 2016.We compared Wip1?knockout (Wip1?KO) mice and wild?type (WT) mice to determine changes in cardiac function and survival in response to MI. The heart weight/body weight (HW/BW) ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending (LAD) coronary artery under 1.5%isoflurane anesthesia.After MI, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin (H&E) staining was used to determine the infarct size. Gene expression of interleukin?6 (IL?6), tumor necrosis factor?α (TNF-α), and interleukin?1β (IL-1β) was assessed by quantitative real?time polymerase chain reaction (qPCR), and the levels of signal transducers and activators of transcription 3 (stat3) and phosphor?stat3 (p?stat3) were also analyzed by Western blotting. Kaplan?Meier survival analysis, log?rank test, unpaired t?test, and one?way analysis of variance (ANOVA) were used for statistical analyses. Results: Wip1?KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac function before LAD ligation. After MI, Wip1?deficient mice exhibited increased mortality (57.14% vs. 29.17%; n = 24 [WT], n = 35 [Wip1?KO], P < 0.05), increased cardiac hypertrophy (HW/BW ratio: 7 days: 7.25 ± 0.36 vs. 5.84 ± 0.18, n = 10, P < 0.01, and 4 weeks: 6.05 ± 0.17 vs. 5.87 ± 0.24, n = 10, P > 0.05;cross?sectional area: 7 days: 311.80 ± 8.29 vs. 268.90 ± 11.15, n = 6, P < 0.05, and 4 weeks: 308.80 ± 11.26 vs. 317.00 ± 13.55, n = 6, P > 0.05), and reduced cardiac function (ejection fraction: 7 days: 29.37 ± 1.38 vs. 34.72 ± 1.81, P < 0.05, and 4 weeks: 19.06 ± 2.07 vs. 26.37 ± 2.95, P < 0.05; fractional shortening: 7 days: 13.72 ± 0.71 vs. 16.50 ± 0.94, P < 0.05, and 4 weeks: 8.79 ± 1.00 vs. 12.48 ± 1.48, P < 0.05; n = 10 [WT], n = 15 [Wip1?KO]). H&E staining revealed a larger infarct size in Wip1?KO mice than in WT mice (34.79% ± 2.44% vs. 19.55% ± 1.48%, n = 6, P < 0.01). The expression of IL?6 and p?stat3 was downregulated in Wip1?KO mice (IL?6: 1.71 ± 0.27 vs. 4.46 ± 0.79, n = 6, P < 0.01; and p?stat3/stat3: 1.15 ± 0.15 vs. 1.97 ± 0.23, n = 6, P < 0.05). Conclusion: The results suggest that Wip1 could protect the heart from MI?induced ischemic injury.

OBJECTIVETo study the effects of inhalation enflurane (Enf) before aortic clamping on myocardial reperfusion injury in cardiac surgery with cardiopulmonary bypass (CPB).

METHODShirty patents undergoing selective cardiac valve replacement were randomly allocated to three groups. Group I and group II inhaled 1.0 MAC and 0.5 MAC Enf before clamping aorta, respectively. Group III was the control group interval administration with Fentanyl.

RESULTSImmediately upon aortic clamp release (T2), the value of CK-MB, MDA and SOD of all the groups was significantly increased, however,their concentration did not peak significantly until T3 and T4(10 and 30 min after clamp aorta release). The levels at 60 min (T5) and 24 hours (T6) aorta were lower than T4 but still higher than T(0). At T3 and T4, CK-MB levels in group I were significantly higher than those in II and III groups (P=0.0220, 0.0108 and 0.0202, 0.0295). At T6, the CK-MB level of group II was significantly higher than that of group III (P<0.0001). At T4 and T5, the MDA value of group I was higher than that of group II (P=0.0060 and 0.0364). Meanwhile, the SOD level in group I was also higher than that of group II and group III at the T4 point (P<0.0001 and 0.0084). There was a correlation between the CK-MB value and the aorta clamping time,correlation coefficient range being 0.55 - 0.81,(P<0.05). However, there was no correlation between the CK-MB and MDA, SOD.

CONCLUSIONThere is ischemia reperfusion injury during cardiac surgery CPB with the increase of OFR production and elevation of the antioxidant reserve. Inhalation of large dose of enflurane may result in increased myocardial ischemia reperfusion injury manifested by elevated levels of myocardial enzymes and OFR production.

Adult ; Aged ; Anesthetics, Inhalation ; adverse effects ; Cardiopulmonary Bypass ; adverse effects ; Creatine Kinase ; blood ; Creatine Kinase, MB Form ; Enflurane ; adverse effects ; Female ; Free Radicals ; Heart Valve Prosthesis Implantation ; adverse effects ; Humans ; Isoenzymes ; blood ; Male ; Malondialdehyde ; blood ; Middle Aged ; Myocardial Reperfusion Injury ; etiology ; Superoxide Dismutase ; blood

Parthenogenetic activation is a procedure that an oocyte at meiosis II stage is activated into mitosis by some chemical or physical stimulation other than a sperm and the embryo is formed in the absence of any contribution from a male gamete. The activation of oocyte is the result of calcium ion oscillations and deactivation of some cytokines such as maturation promoting factor, mitogen-activated protein kinase and cytostatic factor. Parthenogenetic activation is artificially induced by various kinds of physical and/or chemical methods. The main activation method of human oocyte is chemical methods. The rates of activation and cleavage depend on the age, origin,and culture conditions of the oocyte.
Adenine ; analogs & derivatives ; pharmacology ; Animals ; Calcium ; metabolism ; Cycloheximide ; pharmacology ; Cytokines ; metabolism ; Female ; Humans ; Oocytes ; drug effects ; growth & development ; metabolism ; Parthenogenesis ; drug effects

BackgroundSweep pattern visual evoked potential(SPVEP) acuity,as an objective detective technique of visual function,can be used to measure visual acuity in children and uncooperative adults.Recent studies have shown that the amplitude-logarithm of the visual angle (A-LogVA) function regression method was more accurate than the amplitude-spatial frequency (A-SP)function regression method in evaluating SPVEP acuity.Objective This study was to explore the clinical use of SPVEP acuity in visual developing children and compare the evaluating the SPVEP acuity of children between A-SP function regression method and A-LogVA function regression method.Methods Twenty-six eyes of 26 asthenopic children with age range of 3-12 years and 31 age-matched normal children were enrolled in this study.SPVEP acuity was recorded with GT-2000 NV ( GUOTE MEDICAL APPARATUS LTD,China) using sinusoidally modulated horizontal gratings of 10 different spatial frequencies from 0.99 to 12.89 cpd as stimulus.The responses were averaged and displayed through discrete Fourier transformations (DFT) on the monitor display.SPVEP acuity was estimated by using both the SPVEP A-SP function regression method and the SPVEP A-LogVA function regression method.The LogMAR chart was used to acquire LogMAR visual acuity.ResultsIn the normal group,the correlation coefficient between LogMAR visual acuity and acuity calculated by the A-SP function regression method was 0.600 (P＜0.01).The correlation coefficient between LogMAR visual acuity and acuity calculated by the A-LogVA function regression method was 0.733 ( P＜0.01 ).The ANOVA of the LogMAR acuity and the SPVEP acuity calculated from the A-SP function regression method and A-LogVA function regression method were 113.173 (P＜0.01 ),which indicated that there were significant difference among all of subjects.The differences of the mean values of LogMAR visual acuity and the SPVEP acuity calculated from the A-SP function regression method and A-LogVA function regression method were respectively 0.40±0.02,0.26 ±0.02 and 0.14 ± 0.02.In the amblyopia group,the correlation coefficient between LogMAR visual acuity and acuity calculated by the A-SP function regression method was 0.134 (P =0.515 ).The correlation coefficient between LogMAR visual acuity and acuity calculated by the A-LogVA function regression method was 0.456 ( P＜0.05 ).The ANOVA of the LogMAR acuity and the SPVEP acuity calculated from the A-SP function regression method and A-LogVA function regression method were 3.433 (P＜0.05),indicating that there were significant difference among all of subjects.The differences of the mean values of LogMAR visual acuity and the SPVEP acuity calculated from the A-SP function regression method and A-LogVA function regression method were 0.07±0.05,0.12±0.05 and 0.05 ±0.01 respectively.Conclusions SPVEP can evaluate the visual acuity in children,although SPVEP acuity may overestimate or underestimate acuity in comparison with different LogMAR visual acuities.The amplitude-LogVA function regression method is more accurate in extrapolating SPVEP acuity.

Objective To study systemic hematogenic immunoreactions induced by bacterial infections using simulation of natural system.Methods Whole blood 0.2 mL or white blood cells 0.2 mL and plasma(or normal saline)0.3 mL were stimulated by 0.2 mL of yeast and inactivated Bacillus Calmette-Guerin(BCG,5?10~8/mL),respectively,which were incubated at 37℃for 1 h. Interleukin(IL)-8,C3,C4 and chemokine receptor Fy6 were detected by flow cytometry(FCM)and en- zyme-linked immunosorbentassay(ELISA).Results Bacteria could activate red blood cell to modulate IL-8 release from white blood cells in plasma.In nature experimental group,activation rate(37.04?34.84)of IL-8 was significantly higher than that(1.09?0.77)in isolation experimental group.In nature experimen- tal group,value increment(0.01?0.01)of complement C4 was significantly higher than that(-0.0027?0.008)of isolation experimental group(P

0.05).However,in the end of the treatment,the patients in the treatment group scored significantly better with all the scales than the control group(P