Group testing in mediation analysis

We consider the scenario where there is an exposure, multiple biologically defined sets of biomarkers, and an outcome. We propose a new two-step procedure that tests if any of the sets of biomarkers mediate the exposure/outcome relationship, while maintaining a prespecified familywise error rate. The first step of the proposed procedure is a screening step that removes all groups that are unlikely to be strongly associated with both the exposure and the outcome. The second step adapts recent advances in postselection inference to test if there are true mediators in each of the remaining candidate sets. We use simulation to show that this simple two-step procedure has higher statistical power to detect true mediating sets when compared with existing procedures. We then use our two-step procedure to identify a set of Lysine-related metabolites that potentially mediate the known relationship between increased body mass index and the increased risk of estrogen-receptor positive breast cancer in postmenopausal women.     

Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

无环鸟苷亲脂性前体药物脂质体的制备及体外抗病毒活性(英文)

本文通过将无环鸟苷(acyclovir,简称ACV)2’位羟基分别与月桂酰氯或棕榈酰氯进行酯化反应,制得亲脂性前体药物无环鸟苷月桂酸酯和无环鸟苷棕榈酸酯(分别简称为C₁₂-ACV和C₁₆-ACV),使脂质体包封率从ACV的29.9%提高到C₁₂-ACV的95.6%和C₁₆-ACV的97.1%;漏泄实验表明在4℃透析60h后,一半以上的ACV从脂质体中漏泄,而C₁₂-ACV和C₁₆-ACV的滞留率分别为70%和80%;体外抗疱疹病毒的试验中,在最低试验浓度0.044μmol/L时,ACV不显示抗病毒活性,而C₁₆-ACV脂质体抑制细胞病变率达75%,说明前体药物通过与脂质体脂膜的结合增加了药物的进入细胞能力,从而提高了ACV的抗病毒能力。     

Management of bacterial peritonitis and exit‐site infections in continuous ambulatory peritoneal dialysis*

SUMMARY: Peritonitis and exit‐site infections remain the most important limitations to the delivery of continuous ambulatory peritoneal dialysis (CAPD). Contamination of the peritoneum, from endogenous or exogenous sources, is responsible for most peritonitis episodes. Patients usually present with a cloudy bag, although other causes should be distinguished. Clinical suspicion of peritonitis should be followed rapidly by microbiological examination and empirical treatment. Microbiological confirmation allows for subsequent treatment based on sensitivities. Other interventions such as catheter removal may be appropriate in some patients. Exit‐site infections should also be identified and treated early. Peritonitis may be further prevented by adequate exit‐site care, hygienic methods, and techniques to minimise early contamination of the exit site. Mupirocin may also have a role in preventing infections caused by Staphylococcus aureus.     

Traumatic or septic aortic regurgitation: diagnosis by oesophageal echocardiography

Severe aortic regurgitation was discovered in a young man 21 days after blunt chest trauma and after a prolonged febrile state with positive blood cultures. Using transoesophageal echocardiography (TEE), it was possible to make the differential diagnosis between traumatic rupture and endocarditis as the cause of valvular insufficiency. The use of TEE in the initial evaluation of severe thoracic trauma with an unclear clinical picture is recommended. This method is easy to use at the bedside and gives precise information on the aortic valve and the ascending aorta.     

体外循环术后低钾血症370例的护理

1临床资料我院1996-01/2004-12体外循环下行心内直视手术370例,其中先心病240例,冠状动脉搭桥术55例,风心病瓣膜置换术75例,年龄1.5～74.0岁.     

Alcohol, Osteoporosis, and Bone Regulating Hormones

The mechanism of the production of ethanol-associated osteopenia seems to be a direct effect of alcohol on bone cells and an indirect or modulating effect through mineral regulating hormones such as vitamin D metabolites, parathyroid hormone, and calcitonin. The modulating effects of these hormones on bone and mineral metabolism in acute and chronic alcohol consumption is discussed herein. Key Words: Alcohol, PTH, Calcitonin, Vitamin D, Bone.