Development of antisense nucleotides for therapy / 生物医学工程学杂志

Antisense oligonucleotides (ASODN) for therapy is a genetic technology which is based on the base-complementary principle. DNA or RNA sequence synthesized by biotechnology is transferred into the target cells to form mRNA-DNA or mRNA-RNA double strand for inhibiting the expression of target genes. In this way we can control and treat some diseases. The development of antisense oligonucleotides drugs has opened a new area of genetic pharmacology. This paper reviews its classifications, mechanics and its wide application in the treatment of viral infection, tumor and cardiovascular diseases. At the same time we pose the problems that need solving.

Expressions of survivin and caspase-9 in human primary hepatocellular carcinoma tissues and their significances / 吉林大学学报(医学版)

Objective To study the expressions of survivin and caspase-9 in human primary hepatocellular carcinoma(HCC) tissues and their relationship with apoptosis.Methods Immunohistochemical staining was uesed to detect the expressions of survivin and caspase-9 in paraffin sections of 96 cases including 42 HCC tissues,42 paired adjacent noncancerous tissues and 12 normal liver tissues. Apoptosis was detected by TUNEL.Results No immunoreactivity of survivin was seen in normal liver tissues.The positive rates of survivin in HCC and paired adjacent noncancerous tissues were 73.81% and 4.76%,respectively,there was significant difference between two groups(P0.05).The expressions of survivin and caspase-9 in HCC tissues were not associated with age,sex and the size of tumor,but they were directly associated with tumor histological grade and metastasis.Conclusion High expression of survivin in HCC may inhibit apoptosis through depressing the expression of caspase-9,and it is an indicator of independent poor prognosis.

Effect of Paxil and berhomine on poststroke anxiety-depression and neurological recovery / 中国组织工程研究

BACKGROUND: In addition to physical disability, stroke may also result in psychological impairments usually manifested by depression and anxiety.Regardless of the primary or secondary onset of anxiety, anti-depressants should be given for treatment of the anxiety and depression besides routine treatment of the primary condition underlying the symptoms.OBJECTIVE: To compare the effect of different treatment protocols with or without anti-depressants and different anti-depressants on poststroke anxiety and depression as well as the neurological functions.DESIGN: Randomized controlled double-blind clinical trial.SETTING: Departments of Psychiatry and Neurology of the Second Hospital Affiliated to Lanzhou University.PARTICIPANTS: Ninety patients aged 41-72 years with post-stroke anxiety and depression, who were admitted in the Departments of Psychiatry and Neurology of the Second Hospital Affiliated to Lanzhou University between July 1999 and December 2002, were enrolled in this study and randomized equally into Paxil group, imipramine group and control group.METHODS: After emergency management for 1-2 weeks in the acute stage, the stroke patients showed clear consciousness and stable life signs without any understanding problems. Patients in the control group received conventional treatment combined with rehabilitative training, while patients in the other two groups were given additional Paxil (20 mg/day) or imipramine (50-150 mg/day) for totally 12 weeks. The neurological deficits and capacity for independent living of the patients were assessed with Hamilton Depression Scale (24 items) and Hamilton Anxiety Scale (14items) at 2, 4, 8, and 12 weeks during the treatment. A reduction of the score for Hamilton anxiety and depression scale by over 75% suggested a cure of depression and anxiety, 50% but ＜ 75% obvious improvement,25% but ＜ 50% improvement, and ＜ 25% non-response. Basically recovered neurological function was indicated by a reduction of neurological deficit score by 90%-100%, remarkable improvement by 46%-89%, improvement by 18%-45%, and non-response or exacerbation by a reduction less than 17%.MAIN OUTCOME MEASURS: ① Neurological function recovery of recovery of the patients after treatment; ② Poststroke anxiety and depression status before and after treatment; ③ Therapeutic effects on depression,neurological functions, severity of neurological deficit, and capacity of independent living. ④ Adverse events and side effects.RESULTS: One patient in Paxil group and 3 in the control group failed to be available for follow-up study, and 3 patients in imipramine group withdrew from the study due to adverse events, so that 83 cases were analyzed.At 2 and 4 weeks in the treatment, the scores for neurological deficits and capacity for independent living exhibited obvious changes (P ＜ 0.01),which gradually stabilized at 8 and 12 weeks (P ＜ 0.05), and significantly greater improvement in the neurological function and capacity for independent living was observed in Paxil group than in the control group (P＜ 0.01), but the differences between imipramine group and the control group and between Paxil group and imipramine group were not statistically significant (P ＞ 0.05). The scores for Hamilton Depression Scale and Hamilton Anxiety Scale were obviously lower in Paxil group and imipramine group at 2, 4, 8 and 12 week than those in the control group (P＜ 0.01-0.001), but similar between the former two groups at 12 weeks (P＞ 0.05). Paxil and imipramine on resulted in curative rates of anxiety and depression of 86.6% and 85.1%, respectively, which were obviously higher than that of the control group (46.6%); the improvement rate ofneurological function in Paxil group, imipramine group and control groupwas 89.6%, 70.3% and 56.6%, respectively, with that of Paxil groupsignificantly higher than that of the control group (P ＜ 0.01), but the difference between imipramine group and control group was not signifi cant (P ＞ 0.05).CONCLUSION: Patients with poststroke anxiety and depression shouldreceive appropriate interventions with anti-depressants in addition to treat ment of neural function impairment. Paxil and imipramine haye similar effect in treating anxiety and depression, but the former can be for its less side effects, better compliance on the part of patients and good effect inpromoting neurological function recovery.