术前检测患者血液中总蛋白、白蛋白与白细胞介素-1受体拮抗剂作为切口疝修补术后是否出现血清肿的预测指标

患者切口疝修补术后出现血清肿是非常常见的,约占20%～30%,其中10%的患者渗液量超过50ml。出现血清肿并不一定出现并发症,但血清肿患者术后容易出现疼痛不适,尤其是补片感染导致修补手术失败,切口疝复发。对某些患者及时使用细针抽液,甚至是手术治疗都是必要的。医师会根据患者的不同病     

The “LEARn” (Latent Early-life Associated Regulation) model integrates environmental risk factors and the developmental basis of Alzheimer’s disease,and proposes remedial steps

The neurodegenerative disorder Alzheimer’s disease (AD) is the 6th leading cause of death in the USA. In addition to neurological and psychiatric symptoms, AD is characterized by deficiencies in S-adenylmethionine (SAM), vitamin B12, and folate. Deficiency in these nutrients has been shown to result in gene promoter methylation with upregulation of AD-associated genes. While some cases of AD are due to specific mutations in genes such as presenilin 1 (PSEN) and the amyloid-β peptide precursor protein (APP), these familial AD (FAD) cases account for a minority of cases. The majority of genetic contribution consists of risk factors with incomplete penetrance. Several environmental risk factors, such as cholesterol and diet, head trauma, and reduced levels of exercise, have also been determined for AD. Nevertheless, the majority of risk for AD appears to be established early in life. We propose to explain this via the LEARn (Latent Early-life Associated Regulation) model. LEARn-AD (LAD) would be a “two-hit” disorder, wherein the first hit would occur due to environmental stress within the regulatory sequences of AD-associated genes, maintained by epigenetic changes such as in DNA methylation. This hit would most likely come in early childhood. The second hit could consist of further stress, such as head trauma, poor mid-life diet, or even general changes in expression of genes that occur later in life independent of any pathogenesis. Given that the primary risk for LAD would be maintained by DNA (hypo)methylation, we propose that long-term nutritional remediation based on the LEARn model, or LEARn-based nutritional gain (LEARnING), beginning early in life, would significantly reduce risk for AD late in life.     

The impact of donor type and ABO incompatibility on transfusion requirements after nonmyeloablative haematopoietic cell transplantation

We retrospectively analyzed transfusion requirements within the first 100 d among allogeneic haematopoietic cell transplantation (HCT) recipients with haematological malignancies given either myeloablative (n = 1353) or nonmyeloablative conditioning (n = 503). We confirmed that myeloablative recipients required more platelet and red blood cell (RBC) transfusions than nonmyeloablative recipients (P < 0·0001 for both). Myeloablative patients given peripheral blood stem cells required less platelet transfusions (P < 0·0001) than those given marrow while RBC transfusion requirements did not differ significantly. Subsequent analyses were restricted to nonmyeloablative recipients. Platelet and RBC transfusions were less frequent among related compared to unrelated recipients (P < 0·0001 for both), with comparable median numbers of transfused units. Major/bidirectionally ABO‐mismatched recipients required more RBC transfusions than ABO‐matched recipients (P = 0·006). Rates of graft rejection/failure, grades II–IV acute and chronic graft‐versus‐host‐disease (GVHD), 2‐year relapse, 3‐year survivals and non‐relapse mortality were comparable among ABO‐matched, minor‐mismatched, and major/bidirectionally mismatched recipients (P = 0·93, 0·72, 0·57, 0·36, 0·17 and 0·79, respectively). Times to disappearance of anti‐donor IgG and IgM isohemagglutinins among major/bidirectionally ABO‐mismatched recipients were affected by magnitude of pre‐HCT titres (P < 0·001 for both) but not GVHD (P = 0·71 and 0·78, respectively). In conclusion, nonmyeloablative recipients required fewer platelet and RBC transfusions and among them, both unrelated and major/bidirectionally ABO‐mismatched recipients required more RBC transfusions. ABO incompatibility did not affect nonmyeloablative HCT outcomes.     

Mode of cell death induced by the HSP90 inhibitor 17-AAG (tanespimycin) is dependent on the expression of pro-apoptotic BAX

Inhibitors of the molecular chaperone heat shock protein 90 (HSP90) are of considerable current interest as targeted cancer therapeutic agents because of the ability to destabilize multiple oncogenic client proteins. Despite their resulting pleiotropic effects on multiple oncogenic pathways and hallmark traits of cancer, resistance to HSP90 inhibitors is possible and their ability to induce apoptosis is less than might be expected. Using an isogenic model for BAX knockout in HCT116 human colon carcinoma cells, we demonstrate the induction of BAX-dependent apoptosis at pharmacologically relevant concentrations of the HSP90 inhibitor 17-AAG both in vitro and in tumor xenografts in vivo. Removal of BAX expression by homologous recombination reduces apoptosis in vitro and in vivo but allows a lower level of cell death via a predominantly necrotic mechanism. Despite reducing apoptosis, the loss of BAX does not alter the overall sensitivity to 17-AAG in vitro or in vivo. The results indicate that 17-AAG acts predominantly to cause a cytostatic antiproliferative effect rather than cell death and further suggest that BAX status may not alter the overall clinical response to HSP90 inhibitors. Other agents may be required in combination to enhance tumor-selective killing by these promising drugs. In addition, there are implications for the use of apoptotic endpoints in the assessment of the activity of molecularly targeted agents.     

Secondary kill effect of deltamethrin on Triatoma infestans

Control of the Chagas disease vector, Triatoma infestans, relies on the application of pyrethroid insecticides, especially deltamethrin. We performed laboratory studies to determine whether a T. infestans nymph that comes into contact with a deltamethrin-treated surface horizontally transfers the insecticide to subsequent triatomines. We found that a triatomine that walks on a deltamethrin-treated surface for a short period of time has the ability to transport the insecticide in concentrations sufficient to kill other triatomines with which it comes into contact. The effect was limited to high-density environments, and mortality as a result of secondary exposure was greater among second-instar nymphs compared with fifth-instar nymphs. Our results suggest that deltamethrin could be killing triatomines through both direct and indirect contact, although it remains unclear whether the phenomenon occurs in natural conditions.