ADAM33 polymorphisms and susceptibility to allergic rhinitis: a meta-analysis

European Archives of Oto-Rhino-Laryngology - Several polymorphisms in a disintegrin and metalloproteinase 33 (ADAM33) have been implicated in susceptibility to allergic rhinitis (AR), but the...     

Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

Mortality,length of stay and costs associated with acute graft-versus-host disease during hospitalization for allogeneic hematopoietic stem cell transplantation

Objective: Acute graft-versus-host disease (aGVHD) is a common and life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The extent to which aGVHD increases inpatient costs associated with allo-HSCT has not been thoroughly evaluated. In this analysis, mortality, hospital length of stay (LOS) and costs associated with aGVHD during allo-HSCT admissions are evaluated.

Methods: This is a retrospective analysis of discharge records from the National Inpatient Sample database for patients receiving allo-HSCT between 1 January 2009 and 31 December 2013. Allo-HSCT discharges with an aGVHD diagnosis were included in the aGVHD group and those without any graft-versus-host disease (GVHD) diagnosis comprised the non-GVHD group. Mortality, LOS and costs were compared between the two groups, as well as within subgroups, including age (<18 vs. ≥18 years) and survival status (alive vs. deceased) at discharge.

Results: Overall, mortality (16.2% vs. 5.3%; p?<?.01), median hospital LOS (42.0 vs. 26.0 days; p?<?.01) and median total costs ($173,144 vs. $98,982; p?<?.01) were significantly increased in patients with aGVHD versus those without GVHD during hospitalizations for allo-HSCT, irrespective of age group. Patients with aGVHD who were <18 years of age had a lower mortality rate but greater hospital LOS and total costs versus patients aged ≥18 years. Patients who died during allo-HSCT hospitalization had longer LOS and incurred greater costs than those who survived in both the aGVHD and non-GVHD groups.

Conclusion: Occurrence of aGVHD during allo-HSCT admissions resulted in a tripling of the mortality rate and a near doubling of hospital LOS and total costs. In addition, death during allo-HSCT hospitalizations was associated with greater healthcare utilization and costs. Effectively mitigating aGVHD may improve survival and substantially reduce hospital LOS and costs for allo-HSCT.     

髋臼爆裂骨折伴股骨头脱位21例手术治疗体会

目的:通过对21例髋臼爆裂性骨折伴股骨头脱位的手术治疗,探讨处理此类损伤应注意的几个问题。方法:术前 X片及CT片明确骨折及脱位类型,采用患侧扩大的髂股入路或Langenbeck-Kocher入路,显露髂骨内外板及小骨盆内壁、髋臼前后柱,必要时显露坐骨大切迹,保持股骨头于脱位状态,直视下复位各骨折块尽量达到髓关节内软骨面光滑圆弧,在骨折复位状态下行内固定,之后使股骨头复位入髋臼,术后皮牵引,早期锻炼。结果:术后21例随访12～36个月, 骨折均愈合好,髋臼内壁形态光滑,元再脱位或创伤性关节炎症状出现。结论:髋臼爆裂性骨折伴股骨头脱位的病例,早期手术恢复髋臼内壁软骨面光滑圆弧可最大限度的恢复患肢功能,能有效地防止髓关节创伤性关节炎的发生,手术切口的选择是复位成功的关键,同时深静脉栓塞、坐骨神经的损伤及异位骨化的预防应予以重视。     

Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors.

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.     

高压氧综合治疗持续植物状态30例疗效分析

目的评估高压氧综合治疗持续植物状态的疗效和探讨最佳治疗方案。方法回顾性分析了1999年—2005年应用高压氧治疗的30例持续植物状态病例,主要分析了原发病因、高压氧治疗次数以及高压氧治疗时机与疗效的关系。结果脑外伤组显效率和好转率明显高于非脑外伤组(P<0.05),开始治疗时间≤30d组及31～60d组好转率明显高于≥61d组(P<0.05)。结论高压氧综合治疗对脑外伤所致持续植物状态患者60d以内开始行高压氧治疗的患者疗效较好。     

Pick’s disease with Pick bodies combined with progressive supranuclear palsy without tuft‐shaped astrocytes: A clinical,neuroradiologic and pathological study of an autopsied case

We report clinical, neuroradiologic features, and neuropathologic findings of a 76‐year‐old man with coexistent Pick’s disease and progressive supranuclear palsy. The patient presented with loss of recent memory, abnormal behavior and change in personality at the age of 60. The symptoms were progressive. Three years later, repetitive or compulsive behavior became prominent. About 9 years after onset, he had difficulty moving and became bed‐ridden because of a fracture of his left leg. His condition gradually deteriorated and he developed mutism and became vegetative. The patient died from pneumonia 16 years after the onset of symptoms. Serial MRI scans showed progressive cortex atrophy, especially in the bilateral frontal and temporal lobes. Macroscopic inspection showed severe atrophy of the whole brain, including cerebrum, brainstem and cerebellum. Microscopic observations showed extensive superficial spongiosis and severe neuronal loss with gliosis in the second and third cortical layers in the frontal, temporal and parietal cortex. There were Pick cells and argyrophilic Pick bodies, which were tau‐ and ubiquitin‐positive in neurons of layers II–III of the above‐mentioned cortex. Numerous argyrophilic Pick bodies were observed in the hippocampus, especially in the dentate fascia. In addition, moderate to severe loss of neurons was found with gliosis and a lot of Gallyas/tau‐positive globus neurofibrillary tangles in the caudate nucleus, globus pallidus, thalamus, substantia nigra, locus coeruleus and dentate nucleus. Numerous thorned‐astrocytes and coiled bodies but no‐tuft shaped astrocytes were noted in the basal ganglion, brainstem and cerebellar white matter. In conclusion, these histopathological features were compatible with classical Pick’s disease and coexistence with progressive supranuclear palsy without tuft‐shaped astrocytes.