A tumor-targeted and conditionally replicating oncolytic adenovirus vector expressing TRAIL for treatment of liver metastases.

We have constructed a new capsid-modified adenovirus (Ad) vector that specifically replicates in tumor cells and expresses TNF-related apoptosis-inducing ligand (TRAIL). The Ad capsid contains short-shafted fibers derived from Ad serotype 35, which allow for efficient infection of malignant tumor cells, and largely avoids innate toxicity after intravenous application. Replication-dependent homologous recombination in Ad genomes was used to achieve tumor-specific expression of Ad E1a (to mediate viral replication) and TRAIL (to mediate apoptosis and enhance release of progeny virus from infected cells). We demonstrated that our oncolytic vector (Ad5/35.IR-E1A/TRAIL) induced apoptosis in human tumor cell lines derived from colorectal, lung, prostate, and liver cancer. Both in vitro and in vivo tumor models showed efficient intratumoral spread of this vector. In a model for metastatic colon cancer, tail vein infusion of Ad5/35.IR-E1A/TRAIL resulted in elimination of preestablished liver metastases. Intravenous injection of this vector caused a transient elevation of serum glutamic pyruvic transaminase in tumor-bearing mice, which we attributed to factors released from apoptotic tumor cells. Liver histology analyzed at day 14 after virus injection did not show signs of hepatocellular damage. This new oncolytic vector represents a potentially efficient means for gene therapy of metastatic cancer.     

Defective implant osseointegration under protein undernutrition: prevention by PTH or pamidronate.

Protein deficiency is associated with impaired titanium osseointegration. We studied whether systemic treatment with PTH or pamidronate could influence the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. PTH or pamidronate prevented the deleterious effects of protein undernutrition on bone microarchitecture close to the implant and on mechanical fixation. PTH even significantly improved implant osseointegration. INTRODUCTION: Protein deficiency is highly prevalent among elderly patients hospitalized in orthopedic wards. Reduced protein intake impairs titanium osseointegration in rats. Whether stimulator of bone formation or inhibitor of bone resorption could improve implant osseointegration under protein deprivation is not known. We studied the effects of systemic treatment with PTH or pamidronate on the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. MATERIALS AND METHODS: We measured the resistance to pull-out 1-mm-diameter titanium rods implanted into the proximal tibias of 49 adult female rats receiving a normal or an isocaloric low protein diet. After 2 wk on either diet, the implants were inserted, and the rats received PTH(1-34), pamidronate or saline vehicle for 8 wk. The tibias were removed for microCT morphometry, followed by the evaluation of pull-out strength. RESULTS: Pull-out strength was lower in rats fed an isocaloric low protein diet compared with rats fed a normal protein intake (-29%). PTH and pamidronate significantly increased pull-out strength in animals fed a normal or a low protein diet, the effect of PTH being of higher magnitude. The PTH- or pamidronate-mediated increase in pull-out strength was associated with significant increases of relative bone volume, bone-to-implant contact, and trabecular thickness, whereas trabecular spacing was reduced, in the vicinity of the implants. CONCLUSIONS: We confirmed that isocaloric low protein intake impairs titanium implant osseointegration. PTH or pamidronate prevented the deleterious effects of protein undernutrition and even significantly improved the implant osseointegration. These results indicate that systemic administration of PTH or pamidronate could be considered for preventing uncemented arthroplasty loosening in protein undernourished patients.     

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses.

OBJECTIVE: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). METHODS: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. CONCLUSION: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.     

Triptolide inhibits T cell activation and proliferation via multiple pathways

Triptolide is potent immunosuppressive has been reported to inhibit autoimmunity, compound isolated from Chinese herbal medicine. Triptolide allograft attributed to the suppression of T cells via NF - kB rejection and GVHD, and its efficacy was previously pathway and apoptosis. In the present study, we detailedly analyzed Triptolide＇ s function on murine primary T cell. We found that Triptolide could inhibit T cell activation and proliferation by dramatically down - regulating cell division and cell cycle. Triptolide inhibited T cell activation in a dose- dependent manner, and the inhibition was mediated by both NF- kB pathway and AP - 1 pathway.     

胰岛素强化治疗对严重创伤患者炎性反应及预后的影响

Objective To investigate the effects of intensive insulin therapy on inflammatory re-sponse and prognosis of patients with severe trauma. Methods Eighty severely injured patients were di-vided into intensive insulin therapy group (n = 40, IT) and routine therapy group (n = 40, RT) in random pair. At the time of admission, a continuous infusion of insulin (2 -4 U/h) was pumped into the patients of IT group to maintain blood glucose level at 6 -8 mmol/L. Patients in RT group were given routine treatment without administration of insulin. Fever, organ injury, and mortality of patients in 2 groups were recorded. Venous blood was drawn from patients of 2 groups on the morning of post treatment day (PTD) 1, 3, 5, and 7. Values of TNF-α, C-reactive protein (CRP), IL-2, and IL-10 in plasma were assayed. Results High fever appeared in 9 patients in IT group, and WBC exceeded 10.0×109 for more than 3 days in 17 patients in this group, versus 20 and 29 patients respectively in RT group. Dysfunction of 1 organ appeared in 31 pa-tients in IT group and 30 patients in RT group. Dysfunction of 3 organs appeared in 10 patients in IT group and 19 patients in RT group. Dysfunction of 4 organs appeared in 7 patients in IT group and 12 patients in RT group. In IT group, 4 patients died within 3 post-injury day (PID), and 1 patient died after PID 3 (total case fatality: 12.5% ). In RT group, 5 patients died within 3 PID, and 4 patient died after PID 3 (total case fatality: 22.5%). Plasma levels of TNF-α and CRP of patients in IT group were significantly lower than those of patients in RT group on PID 3 - 7 ( P<0.05 or P<0.01 ), while levels of IL-2 and IL-10 of patients in IT group were significantly higher than those of patients in RT group ( P<0.05 or P<0.01 ). Plasma levels of TNF-α ( 1.3±0.6 μg/L) and CRP (55±16 mg/L) of patients in IT group on PTD 7 were lowered to the trough level, and they were significantly lower than those of patients in RT group (3.0±0.8μg/L, 89±20 mg/L, respectively, P <0.01 ). Conclusions Intensive insulin therapy can mitigate systemic inflammatory response and improve prognosis of patients with severe trauma.     

抗人热休克蛋白60效价增高提示急性心源性胸痛患者的一年预后不良

目的：探讨抗人热休克蛋白60或抗分枝杆菌热休克蛋白65抗体是否能够预测因急性心源性胸痛入院的患者一年预后不良。设计：前瞻性观察研究。地点：教学医院。患者：连续588例急诊收治的疑似急性心源性胸痛患者。主要观察指标：测定入院后晨起血样的抗人热休克蛋白60和抗分枝杆菌热休克蛋白65效价。出院后终点为冠心病死亡、非致死性心肌梗死、冠状动脉搭桥术、经皮穿刺腔内冠状动脉成形术、血管造影或因心脏缺血性胸痛加重再次入院。     

深静脉血栓形成患者凝血因子ⅩⅢ Val34Leu基因多态性检测

目的:探讨凝血因子ⅩⅢ(FⅩⅢ)Val34Leu基因多态性与中国人群深静脉血栓形成(DVT)发病的相关性.方法:利用聚合酶链反应和限制性片段长度多态性(PCR-RFLP)方法,检测了103例DVT患者与106例正常对照的FⅩⅢVal34Leu基因多态,并加以对照分析.结果:103例DVT患者FⅩⅢVa134Leu基因型均为野生型V/V,未见突变类型;106例对照组中发现1例突变杂合子V/L.2组基因型频率、等位基因频率相互比较,差异均无统计学意义(P＞0.05).结论:FⅩⅢVal34Leu对中国人群DVT有保护作用的可能性极小.     

Serial CT findings of Paragonimus infested dogs and the Micro-CT findings of the worm cysts.

OBJECTIVE: To investigate the serial CT findings of Paragonimus westermani infected dogs and the microscopic structures of the worm cysts using Micro-CT. MATERIALS AND METHODS: This study was approved by the committee on animal research at our institution. Fifteen dogs infected with P. westermani underwent serial contrast-enhanced CT scans at pre-infection, after 10 days of infection, and monthly thereafter until six months for determining the radiologic-pathologic correlation. Three dogs (one dog each time) were sacrificed at 1, 3 and 6 months, respectively. After fixation of the lungs, both multi-detector CT and Micro-CT were performed for examining the worm cysts. RESULTS: The initial findings were pleural effusion and/or subpleural ground-glass opacities or linear opacities at day 10. At day 30, subpleural and peribronchial nodules appeared with hydropneumothorax and abdominal or chest wall air bubbles. Cavitary change and bronchial dilatation began to be seen on CT scan at day 30 and this was mostly seen together with mediastinal lymphadenopathy at day 60. Thereafter, subpleural ground-glass opacities and nodules with or without cavitary changes were persistently observed until day 180. After cavitary change of the nodules, the migratory features of the subpleural or peribronchial nodules were seen on all the serial CT scans. Micro-CT showed that the cyst wall contained dilated interconnected tubular structures, which had communications with the cavity and the adjacent distal bronchus. CONCLUSION: The CT findings of paragonimiasis depend on the migratory stage of the worms. The worm cyst can have numerous interconnected tubular channels within its own wall and these channels have connections with the cavity and the adjacent distal bronchus.     

老年人与青年人皮肤血流量比较研究

目的 判定增龄对皮肤血流量的影响。方法 用PIM2-LDPI检测皮肤血流量。结果 老年组前额、左手指背、命门穴部位皮肤血流量分别为:(1.94±0.86)V,(1.92±0.52)V和(0.71±0.19)V,与青年组比较差异无显著性。但是,老年男性在命门穴的皮肤血流量明显高于青年男性(P<0.05),老年女性前额的皮肤血流量明显降低(P<0.01)。男性比女性的皮肤血流量高。结论 皮肤血流量的差异无年龄相关性,男性组的皮肤血流量比女性组高。