Objective Tissue engineering advance in supplying the reparative and reconstructive medicine with promising tissue engineered medical products(TEMPs) and the new therapy alternative. The related supervision and administration of TEMPs is being developed and the standard research of TEMPs is also in progress. The Food and Drug Administration(FDA) of the United States has treated TEMPs as combined products and supervised them according to the level of risk to patients. Lately, FDA has determined that the Center for Devices and Radiological Health (CDRH) should take charge of examination and approval of TEMPs, with the cooperation of the Center for Biological Evaluations and Research(CBER). The regulatory controls have been established respectively in European Union and Japan. In China, TEMPs are identified as medical devices combined with cells. The Department of Medical Device of the State Food and Drug Administration (SFDA) is responsible for the examination and approval of TEMPs, and National Institute for the Control of Pharmaceutical amp; Biological Products(NICPBP) is responsible for evaluation tests. The standards of TEMPs are formulated mainly by the American Society of Testing Materials(ASTM) and International Standardization Organization(ISO).
ObjectiveTo evaluate the security of intravitreal injection with ciproflaxacin to retina.MethodsTweenty-four rabbits were randomly divided into 4 groups with 6 rabbits in each group. 0.1 ml ciproflaxacin in doses of 2 500,5 000,and 10 000 μg was intravitreally injected into the rabbits eyes, retrospectively. And 0.1 ml saline solution was injected into the vitreous body of the rats in the control group. Indirect microscope, light microscope and electroretinogram (ERG) were used to observe the changes of ocular fundus.ResultsNormal results of light microscopy and ultrastructure were found in 250 μg and 500 μg groups; irregularly arranged outer and inner nuclear layers, dropsical or even lost ganglion cells, and ultrastructural changes were in 1 000 μg group. There was no apparent difference of ERG′s a and b amplitudes before and after intravitreal injection with ciproflaxacin in each group.ConclusionIntravitreal injection with ciproflaxacin is safe, and 500 μg or less is the secure dosage in rabbits' eyes. (Chin J Ocul Fundus Dis, 2005,21:180-182)
Objective To observe the effect of medicineinduced posterior vitreous detachment (PVD) on proliferative vitreoretinopathy (PVR). Methods PVR was induced in the left eyes of 24 pigmented rabbits by intravitreal injection with platelet rich plasma. The rabbits were randomly divided into two experimental groups (group A and B) and one control group with 8 eyes in each group. Three hours later, the eyes in group A and B and the control group underwent intravireal injection with 1 U plasmin 0.05 ml+20 U hyaluronidase 0.05 ml, plasmin 0.1 ml, and balance salt solution 0.1 ml, respectively. The grade of PVR was recorded 1, 7, and 28 days after the intravitreal injection, and the eyes were examined by flash electroretinogram (FERG), B-scan, and retinal histopathological examination. Results The PVR models of rabbit eyes were induced successfully. On the 7th day after injection, complete and partial PVD was found in 5 and 3 eyes respectively in group A; partial PVD in 5 eyes and no complete PVD was observed in group B; there was no PVD in the other 3 eyes in group B and also in the eyes in the control group. On the 28th day after intravitreal injection, PVR grade of group A and B were both obviously lower than that of the control group（D=75.6, 98.9；P=0.003，P=0.011）; On the 7th and 28th day after injection, the b-wave amplitude in group A and B was significantly higher than that in the control group; PVR grade of the PVD eyes was lower than that of nonPVD eyes; PVR grade of the complete PVD eyes was only 0～1. Conclusions Three hours after the PVR models of rabbit eyes were induced, complete PVD induced by intravitreal injection of plasmin combined with hyaluronidase could prevent the development of PVR of rabbit eyes in some degree; partial PVD induced by plasmin alone or combined with hyaluronidase could relieve the development of PVR.
ObjectiveTo suggest the importance of taking notice of oral chemotherapy drugs in cancer patients, and the importance of drug-use evaluation in patients with insufficient kidney functions, by reporting one death case caused by multiple organ failure because of myelosuppression after oral tegafur, gimeracil and oteracil potassium (S-1) capsules for 10 days in a patient with insufficient kidney functions. MethodsThrough the analysis of one patient who died of multiple organ failure due to degree-Ⅳ myelosuppression and the related literature review, we discussed the necessity of individualized administration of clinical chemotherapy. ResultsThe patient had grade-Ⅱ renal insufficiency before chemotherapy and did not undergo dihydropyrimidine dehydrogenase (DPYD) gene test. Myelosuppression occurred 10 days after oral chemotherapy drugs. The white blood cells, neutrophils and platelets decreased progressively, and then developed into degree-Ⅳ suppression. Finally the patient died of multiple organ failure. Conclusions Genetic variation and renal insufficiency may cause differences in drug metabolism. The reduced urinary excretion of guimet pyrimidine (CDHP), the inhibitors of dihydropyrimidine dehydrogenase which is the 5-fluorouracil (5-FU) metabolic enzyme, may lead to elevated plasma concentration of 5-FU, thereby increasing myelosuppression and other adverse reactions. If DPYD gene detection results show low enzyme activity, it can cause lethal toxicity through deceleration of 5-FU metabolism and high concentration of blood. DPYD gene dzetection should be performed if allowed, and individualized treatment plan should be formulated after comprehensive evaluation. The overall situation of the patients should be considered before treatment, and then individualized drugs should be administered.
Objective To explore the effect of restrictive fluid administration on elderly patients with colorectal cancer in fasttrack.Methods From January 2008 to January 2009, the elderly patients (≥60 years old) diagnosed definitely as colorectal cancer were analyzed retrospectively, the clinical effects on post-operative early rehabilitation were studied and the difference between restrictive fluid regimen and tradition fluid regimen was compared. Results The difference of overall incidence of post-operative complications was statistically significant between the two groups (Plt;0.05). The incidences of anastomotic leakage and pulmonary infection of fluid restriction group were lower than those of tradition therapy group (Plt;0.05). The time of vent to normal, defecation to normal and postoperative first eating of fluid restriction group was shorter than those of tradition therapy group, the difference was statistically significant (Plt;0.05). Comparing the biochemical indicators, the difference of preoperative GLU 〔（6.70±2.93） mmol/L vs. （6.33±3.95） mmol/L〕, BUN 〔(5.84±2.03) mmol/L vs. （7.32±10.83） mmol/L〕and CREA 〔(76.19±19.85) μmol/L vs. （85.36±38.02） μmol/L)〕 was statistically significant (Plt;0.05), but the difference of postoperative results had no statistical significance. Conclusion Restrictive fluid regimen can reduce the incidence of common complications after colorectal surgery for elderly patients, and have a certain promoter action to the early rehabilitation after rectal surgery.
The suprachoroidal space (SCS) is the potential space between the sclera and choroid. Drugs delivered through SCS can bypass the sclera, avoiding clearance by conjunctival and scleral blood vessels and lymphatic circulation, so that more drugs can reach the disease tissues such as choroid and retina. SCS drug delivery does not disrupt the ocular integrity, is safer than the intravitreal drug injection and more effective than trans-scleral drug delivery. In addition, SCS delivery only needs a very small volume of drug, which makes it possible to be carried out in multiple parts of the sclera, and the specific disease area can be more precisely targeted. SCS drug delivery is suitable for the treatment of choroidal and retinal diseases. However, currently SCS drug delivery is still a novel field and many aspects need to be more in-depth studied, including its safety, delivery methods, drug formulation and effectiveness.
Objective To observe the influence of cisplan on the expression of B7-H1 in retinoblastoma (RB) cells，and to investigate its mechanism. Methods Human RB cell line HXO-Rb44 cells were treated by 6 different concentrations of cisplan (0.000, 0.375, 0.750, 1.500, 3.000, 6.000 mu;g/ml), and their B7-H1 mRNA expression was determined by the reversetranscription polymerase chain reaction (RT-PCR) and fluorescence quantitative PCR (FQ-PCR); the B7-H1 protein expression was determined by immunofluorescence and flow cytometry. HXO-Rb44 cells were treated by 1.5 mu;g/ml cisplan for 0, 15, 30, 60, 120 min, then the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) was detected by Western blot.Results The expression of B7-H1 mRNA and protein in the 0.375, 0.750, 1.500, 3.000, 6.000 mu;g/ml group were significantly higher than that of the blank control group (F=395.478，112.03; P=0.000）. Western blot showed that cisplan (1.5 mu;g/ml) could activate ERK1/2 by increasing its phosphorylation in HXO-Rb44 cells. After cisplan treatment, the phosphorylation of ERK1/2 increased gradually and reached its peak at 30 min, and then went down gradually.Conclusion Cisplan can promote the expression of B7-H1 and activate ERK1/2 in RB cells.
In January 2020, the State Food and Drug Administration issued the guiding principles of real world evidence supporting drug research & development (R&D) and evaluation (Trial) to guide the development of real world study (RWS) for drug R&D and review decision-making in the future. This guideline has important reference value for developing RWS of health food. Based on the interpretation of the core content of the guiding principles, combined with the common points of RWS and health food interventions, this paper preliminarily discusses the application of RWS to support health food regulatory decision-making so as to provide references for further promoting the application of RWS in the field of health food.
Objective To compare the analgesic effects of fentanyl, tramadol and flurbiprofen axetil during vitrectomy under local anesthesia. Methods One hundred and twenty patients who underwent vitrectomy were randomly divided into four groups, 30 patients in each group. Control group (Group C): normal saline were given; Fentanyl group （group F): fentanyl 1 mu;g/kg; Tramadol group （group T): tramadol 1 mg/kg; Flurbiprofen group （group K): flurbiprofen axetil 1 mg/kg. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2), sedation classification (OAA / S) and pain score (NRS) were recorded prior to drug administration (T0) and the beginning of surgery (T1), 5 min (T2), 15 min(T3), 30 min (T4) and the end of surgery (T5) . The incidence of analgesic remedy and adverse reactions were also recorded after surgery. Results In group F, MAP at T1 and T2 were significantly lower than T0 and that of the other three groups at the same time point (F=5.367,5.967;P＜0.05). MAP at each time point of the other three groups had no significant changes (P＞0.05). In Group C, HR decreased significantly at T3and T4compared to T0 (F=7.900, 6.767;P＜0.05). In Group F, HR decreased significantly at T2 compared to T0 (F=3.117，P＜0.05). HR at each time point of group T and group K had no significant changes (P＞0.05). In group F, SpO2at T1 was significantly lower than T0 and that of the other three groups at the same time point (F=7.352, P＜0.05). SpO2of group F, group T and group K had no significant changes within groups (P＞0.05). In Group F, the median of OAA / S classification at T1 were grade four, which were lower than that at T0 and that of the other three groups at the same time point (chi;2=12.935, P＜0.05). There was no significant changes of the median of OAA / S classification at each time point in the other three groups (P＞0.05). In group C, the median of NRS score was three at T1 and was two at T2 respectively, which were higher than that at T0 and that of Group F and group T at the same time point (chi;2=13.748,11.616; P＜0.05). There were no significant changes of the median of NRS score in group F, group T and group K within groups (P＞0.05). Analgesic remedy percentages in group C, group F, group T and group K were 16.7%, 3.3%, 3.3%, 6.7%, respectively. The incidence of adverse reactions in group C, group F, group T and group K were 30.0%、23.3%、3.3%、16.7%, respectively.Conclusion Tramadol had efficient analgesic effects and low rate of adverse reactions during vitrectomy under local anesthesia.
Objective To investigate the therapeutic effects of throm bolytic drug infusion via carotid artery on experimental central retinal artery occlusion (CRAO), and observe the changes of fibrinolytic activity in the system ic circulation. Methods To dissolve the thrombi in 15 cats (30 eyes) with CRAO established by laser irradiating a branch of central retinal a rtery after intravenous injection of photochemical drugs, urokinase (UK) was dir ectly infused via carotid artery in 5 cats (10 eyes) in group A or intravenously injected in 5 cats (10 eyes) in group B, and isotonic saline solution was intra venously injected in 5 cats (10 eyes) in group C respectively. The patency of the artery was evaluated by fundus fluorescein angiography. Moreover, the changes of fibrinolitic activity in the blood were observed by blood biochemical examination. Results Four hours after UK infusion, the complete repatency proportion was 80% (5 cats 8 eyes) in group A, and 50% (4 cats 5 eyes) in group B. There was significant difference between the two groups. Besides, after the infusion, the indexes of coagulation, fibrinolysis, and anti-fibrinolysis in group A were better than those in group B and C (Plt;0.01). Conclusion In the treatment of experimental CRAO, thrombolytic drug infusion via carotid artery is better and more effective than via intravenous injection, which may provide a new method of thrombolytic drug delivery and animal models. (Chin J Ocul Fundus Dis，2004，20：186-188)