Prognostic analysis and nomogram construction for older patients with IDH-wild-type glioblastoma.

As many countries face an ageing population, the number of older patients with glioblastoma (GB) is increasing. Thus, there is an urgent need for prognostic models to aid in treatment decision-making and life planning. A total of 98 patients with isocitrate dehydrogenase (IDH)-wild-type GB aged ≥65 years were analysed from January 2012 to January 2020. Independent prognostic factors were identified by prognostic analysis. Using the independent prognostic factors for overall survival (OS), a nomogram was constructed by R software to predict the prognosis of older patients with IDH-wild-type GB. The concordance index (C-index) and receiver operating characteristic (ROC) curve were used to assess model discrimination, and the calibration curve was used to assess model calibration. Prognostic analysis showed that the extent of resection (EOR), adjusted Charlson comorbidity index (ACCI), O6-methylguanine-DNA methyltransferase (MGMT) methylation status, postoperative radiotherapy, and postoperative temozolomide (TMZ) chemotherapy were independent prognostic factors for OS. MGMT methylation status and subventricular zone (SVZ) involvement were independent prognostic factors for progression-free survival (PFS). A nomogram was constructed based on EOR, ACCI, MGMT methylation status, postoperative radiotherapy and postoperative TMZ chemotherapy to predict the 6-month, 12-month and 18-month OS of older patients with IDH-wild-type GB. The C-index of the nomogram was 0.72, and the ROC curves showed that the areas under the curve (AUCs) at 6, 12 and 18 months were 0.874, 0.739 and 0.779, respectively. The calibration plots showed that the nomogram was in good agreement with the actual observations in predicting the OS of older patients with IDH-wild-type GB. Older patients with IDH-wild-type GB can benefit from gross total resection (GTR), postoperative radiotherapy and postoperative TMZ chemotherapy. A high ACCI score and MGMT nonmethylation are poor prognostic factors. We constructed a nomogram including the ACCI to facilitate clinical decision-making and follow-up interval selection.

The percutaneous permeability and absorption of dexamethasone esters in diabetic rats: a preliminary study.

To evaluate the influence of diabetes on the permeation of dexamethasone acetate (DA) and dexamethansone sodium phosphate (DSP), the two major dexamethansone esters in clinical practice, when applied percutaneously, histochemical staining was used to determine the skin morphology; improved Franz diffusion cells and microdialysis were used to assess the percutaneous permeation of DA and DSP in normal and diabetic rats. Histopathological examination showed that the epidermal tissue of diabetic rat was much thinner, the epidermal cell layer was less clear and the stratified arrangement of epidemic cell had almost disappeared and progressive atrophy were developed on the subcutaneous fat. In vitro studies showed that the cumulative and the penetrated DSP amount in Group DM were higher. The mean flux value and the mean depositional amount of Group DM were increased significantly compared to those of Group CTL, whereas the amount of DA penetrating was of no difference. Microdialysis indicated that there was no significant difference between Group CTL and Group DM for all the pharmacokinetic parameters of DA. In contrast, the subcutaneous AUCall values and the C(max) of DSP were significantly increased compared to the control. In conclusion, diabetic rat skin significantly increased the percutaneous permeation of DSP but had no effect on that of DA. It suggests that patients with diabetes should consider the dose of administration when using DA, DSP or other glucocorticoids topically, as different liposolubilities may play some role in the permeability of these compounds via diabetic skin.

[On-line detection of hydrocortisone concentration in rat subcutaneous adipose with liquid chromatography-mass spectrometry/mass spectrometry].

OBJECTIVE: To develop a method for detecting the topical concentration of hydrocortisone (HC) in the subcutaneous adipose of rats using microdialysis sampling technique and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). METHODS: Topical samples were collected by applying the probe into the subcutaneous adipose of rats, with alcohol (5%)-ringers solution as the perfusion solution. A LC-MS/MS method was established for detecting the HC concentration in the dialysates. RESULTS: The protonated precursor to produce ion transitions monitored for HC was m/z 363.2→121.1. The calibration curve was linear over the range of 0.5-1000 ng/ml, with the intra- and inter-day precision and accuracy within ∓15%, and no significant matrix effect was noted. The in vivo recovery of the probe was about 59%. CONCLUSION: A selective and sensitive method has been successfully established for the on-line HC detection in the subcutaneous adipose of rats.

[The histological changes of diabetic rats' skin and the effects on the percutaneous absorption of glucocorticoid].

To examine the histological changes of diabetic rats' skin and the effects on the percutaneous absorption of hydrocortisone (HC, a glucocorticoid), male Wistar rats were randomly divided into five groups: control group, diabetes one-week group (W1), two-week group (W2), three-week group (W3), and four-week group (W4), while each group contained 6 rats. Diabetes mellitus (DM) rat model was prepared with the method of streptozocin (STZ, 40 mg x kg(-1)) intraperitoneal injection. Abdominal skin was cut to carry out an in-vitro penetration experiment on an improved Franz diffusion cells, and phosphate buffer (PBS, pH 7.4) was used as receptor solution. The solution was analyzed with HPLC, and then the penetrating rate can be calculated. Meanwhile, rats' abdominal skins of different DM periods were HE stained and made into tissue slices to find if any histological changes occurred. The penetrating rate of control, W1, W2, W3, and W4 groups were 2.39 +/- 1.25, 3.22 +/- 1.72, 3.02 +/- 1.89, 3.63 +/- 2.02 and 5.00 +/- 3.36 microg x h(-1) x cm(-2), respectively. There was significant difference between the control and the W4 group (P < 0.05), but no significant differences were found between any other two groups (P > 0.05). The tissue slices showed that compared to the normal rats' skin, little change was observed in one-week DM rats' skin, but the skin of one-month DM rats' skin was observed thinner, and it became much thinner than that of rats with two-month diabetes, especially the epidermis. After making a rat into diabetic, the rats' skin goes through a pathological change, and this change is closely interrelated with the increase of the permeation of HC. Therefore, it is necessary to adjust the dose while some drug was applied on the skin in case of diabetes mellitus.