肿瘤自杀基因治疗研究进展

INTRODUCTIONInrecentyears，withtherapiddevelopmentofmolecularbiologyandmoleculargenetics，genetreatmentofmalignanttumorshasbecomeahottopic．Genetreatmentsofmalignanttumorsmainlyincludeim－munegenetreatment，suicidegenetreatment，carcinoma－inhibitinggenetreatment犤１犦，andmultidrugtolerancegenetreatmentofhematopoieticstemcellsetc．Ofthese，thespecialbystandereffectsofthesuicidegenetreatmentmakesupforthedefectoflowefficacyoftransfectionmakingthetreatmentrelativelyeffectiveandpotentialtreat…     

Role of GABAergic antagonism in the neuroprotective effects of bilobalide

Many studies suggest that the 5-HT6 receptors are involved, along with other 5-HT receptors, in the pathophysiology and pharmacotherapy of schizophrenia. It is a putative therapeutic target of atypical antipsychotic drugs, notably clozapine, as well as some other psychotropic agents. Preferential potentiation of dopamine (DA) efflux in the medial prefrontal cortex (mPFC) and hippocampus (HIP) has been suggested to contribute to the ability of atypical antipsychotic drugs (APDs), e.g. clozapine, risperidone, olanzapine and ziprasidone, to improve cognitive function in schizophrenia. The present study demonstrated that SB-399885, a selective 5-HT6 receptor antagonist, at doses of 3 and 10 mg/kg, had no effect on cortical DA release in freely moving rats. However, both doses of SB-399885 slightly but significantly increased DA release in the HIP. Of particular interest, SB-399885, 3 mg/kg, significantly potentiated the ability of a typical antipsychotic drug haloperidol, a D2 receptor antagonist, at a dose of 0.1 mg/kg, to increase DA release in the HIP but not the mPFC. The atypical antipsychotic drug risperidone, a multireceptor antagonist, which lacks 5-HT6 receptor antagonist properties, at doses of 0.1, 0.3 and 1.0 mg/kg, produced a bell-shaped dose response effect on DA efflux in the mPFC and HIP. SB-399885 potentiated risperidone (1.0 mg/kg)-induced DA efflux in both regions. The increase in the HIP, but not the mPFC, DA efflux by 0.3 mg/kg risperidone was also potentiated by SB-399885, 3 mg/kg. These results suggest that the combined blockade of 5-HT6 and D2 receptors may contribute to the potentiation of haloperidol- and risperidone-induced DA efflux in the mPFC or HIP. The present data provides additional evidence in support of a possible therapeutic role for 5-HT6 receptor antagonism, as an addition on therapy, to enhance cognitive function in schizophrenia.     

Increased comorbidities in heart failure patients ≥ 85 years but declined from > 90 years: Data from the Swedish Heart Failure Registry

Objectives

Epidemiological studies of elderly heart failure (HF) patients (≥ 85 years) are limited with inconsistent findings. Our objective is to confirm and extend epidemiological study in elderly (≥ 85 years) patients using the Swedish Heart Failure Registry database.

Methods

This retrospective study included 8,347 HF patients aged ≤ 65 years and 15,889 HF patients aged ≥ 85 years. Elderly population was further divided into two subgroups: 11,412 patients were 85–90 years and 4,477 patients were > 90 years.

Results

The ≥ 85 year group was characterized by more women, higher systolic blood pressure (SBP), lower body-mass index (BMI), more than twice as many HF with normal left ventricular ejection fraction (HFNEF), higher incidence of cardiovascular and non-cardiovascular comorbidities and less use of proven therapeutics compared with the ≤ 65 year group. Compared with the 85–90 year subgroup, the > 90 year subgroup had a decline in cardiovascular and non-cardiovascular comorbidities except renal insufficiency and anaemia which continued to increase with ageing (p < 0.01). Tendency was the same regardless of gender but slightly different between systolic HF (SHF) and HFNEF. In the group with HFNEF, there were more women, higher SBP, lower N-terminal pro-B-type natriuretic peptide levels, less ischaemic heart disease, more hypertension and left bundle branch block regardless of age. Atrial fibrillation was more frequent in patients with HFNEF than with SHF in the elderly group (p < 0.01). Patients with HFNEF in the > 90 year subgroup had increasing incidence of ischaemic heart disease compared to 85–90 year group (p < 0.01).

Conclusions

HF patients ≥ 85 years had increased cardiovascular and non-cardiovascular comorbidities but with a decline from > 90 years.     

Engineered Andrographolide Nanoparticles Mitigate Paracetamol Hepatotoxicity in Mice

Purpose

Paracetamol (acetaminophen, APAP) overdose is often fatal due to progressive and irreversible hepatic necrosis. The aim of this work was to design Andrographolide (AG) loaded nanoparticles to prevent similar hepatic necrosis.

Methods

Functionalized AG-loaded PLGA nanoparticles carrying different densities of heparin were prepared following a facile emulsion solvent evaporation technique. Nanoparticle morphology, loading and release kinetics were studied. Hepatic localization of the nanoparticles was investigated in both normal and APAP damaged conditions using FITC fluorescent probe. Different serum parameters and liver histopathology were further examined as indicators of hepatic condition before and after treatment.

Result

A collection of heparin functionalized AG-loaded PLGA nanoparticles were designed. Low amount of heparin on the particle surface could rapidly localize the nanoparticles up to the liver. The new functionalized AG nanoparticles affect efficient hepatoprotection in experimental mouse APAP overdose conditions. AG nanoparticle hepatoprotection was due to the rapid regeneration of antioxidant capacity and hepatic GSH store.

Conclusions

Engineered nanoparticles loaded with AG provided a fast protection in APAP induced acute liver failure.     

Determination of the Hepatic Blood Flow in Man by Simultaneous Use of Five Test Substances Measured in Two Parts of the Liver

Transvascular escape rate of albumin (TER_alb, i.e. the fraction of intravascular mass of albumin (IVM_alb) passing to (or during steady state returning from) the extravascular space per unit time) was determined from the initial disappearance rate of i.v. injected radioiodinated serum albumin in anaesthetized pigs during control conditions and during diuretic medication (furosemide i.v. 20 mg/15 min, total 160–200 mg). During diuretic medication TER_alb (mean 17.1% IVM_alb · h^-1, range 11.5–21, n = 6) increased significantly above the control period (mean 12.3% IVM_alb · h^-1, range 9.5–16.5, P<0.05). Pressures in artery, right atrium, hepatic and portal veins did not change significantly from control to diuretic period. TER_alb equals the lymphatic return rate of albumin provided the transport mechanisms are filtrative-convective (i.e. no local back transport). Additional measurements in five pigs with proteins of different molecular size confirmed a dominating filtrative-convective transport. The increased TER_alb during diuretic medication is best explained by an increased lymph drainage, which may decrease interstitial fluid pressure and thereby increase the transmural capillary pressure difference being essential for a filtrative-convective transvascular albumin transport. Increased lymph drainage may contribute to the therapeutic effect of diuretic treatment in oedema and ascites.     

Depression, anxiety and health status after hospitalisation for COPD: a multicentre study in the Nordic countries

Patients with chronic obstructive pulmonary disease (COPD) often report anxiety, depression and poor health status, not least if they experience repeated hospitalisations due to acute exacerbations. The aim of this study was to analyse the interrelationships between health status, anxiety, depression and physical status in COPD patients being discharged after hospitalisation. This was a prospective study of 416 patients in five university hospitals in each of the Nordic countries. Data included demographic information, lung function and co-morbidity. The Hospital Anxiety and Depression Scale and St. George's Respiratory Questionnaire (SGRQ) were applied to all patients. Both anxiety and depression were common among these patients. Anxiety was more common in women than in men (47% vs. 34%, P=0.009) and current smokers had a higher prevalence of both anxiety (54% vs. 37%) and depression (43% vs. 23%) than non-smokers (P<0.01). In general, the studied COPD patients had poor health status, especially those with anxiety, depression or both. Psychological status was independently related to all dimensions of SGRQ. Higher GOLD stages were significantly associated with increasing impairment in health status. In conclusion this multicentre study showed that anxiety and depression are common in patients with COPD, and, furthermore, that patients with psychological disorders have poor health status. Screening for depression and anxiety may help to identify patients with poor quality of life and an urgent need for intervention in order to improve their health status.     

Nutritional status, dietary energy intake and the risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD)

Loss of body weight, as a result of imbalance between increased energy demand and/or reduced dietary intake, is a common problem in patients with COPD. The aim of this investigation was to examine the relationship between nutritional intake, change in body weight and the risk of exacerbation in patients with COPD. The study comprised 41 patients who were hospitalised because of an exacerbation of COPD. The follow-up period was 12 months. Weight, height and lung function were measured at baseline. At the 12-month follow-up, weight change and current weight were assessed by an interview and nutritional intake was recorded in a food diary for 7 days. An acute exacerbation was defined as having been admitted to hospital and/or making an emergency visit to hospital, due to COPD during the follow-up period. At baseline, 24% of the patients were underweight (body mass index (BMI)<20 kg/m2), 46% were of normal weight (BMI 20-25 kg/m2) and 29% were overweight (BMI>25 kg/m2). Energy intake was lower than the calculated energy demand for all groups. During the follow-up period, 24 of the 41 patients had an exacerbation. A low BMI at inclusion and weight loss during the follow-up period were independent risk factors for having an exacerbation (P=0.003 and 0.006, respectively). We conclude that, in patients who are hospitalised because of COPD, underweight and weight loss during the follow-up period are related to a higher risk of having new exacerbations.     

耳内镜下同种异体羊膜鼓膜修补术的疗效观察

目的:探讨耳内镜下同种异体羊膜鼓膜修补术的临床疗效。方法:回顾性分析在第四军医大学唐都医院行耳内镜下同种异体羊膜鼓膜修补术患者43例(43耳)的临床资料,观察鼓膜穿孔的愈合情况及听力改善情况。结果:43耳中有41耳鼓膜完全愈合,穿孔愈合率95.3%。复查纯音测听,语言频率气导平均听阈较术前提高10dB。随访1～4年,未见再穿孔及其他并发症发生。结论:耳内镜下鼓膜修补术适用于言语频率听阈在40dB以内的单纯鼓膜修补,不仅能修补紧张部中央性穿孔,而且对大部分有残余鼓膜的边缘性穿孔也可修补。人羊膜是鼓膜修补的理想材料。