Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells

Objective25-Hydroxycholesterol (25HC) and its sulfated metabolite, 25-hydroxycholesterol-3-sulfate (25HC3S), regulate certain aspects of lipid metabolism in opposite ways. Hence, the enzyme for the biosynthesis of 25HC3S, oxysterol sulfotransferase (SULT2B1b), may play a crucial role in regulating lipid metabolism. We evaluate the effect of 25HC sulfation on lipid metabolism by overexpressing the gene encoding SULT2B1b in human aortic endothelial cells (HAECs) in culture.Methods and resultsThe human SULT2B1b gene was successfully overexpressed in HAECs following infection using a recombinant adenovirus. HPLC analysis demonstrated that more than 50% of ³H-25HC was sulfated in 24 h following overexpression of the SULT2B1b gene. In the presence of 25HC, SULT2B1b overexpression significantly decreased mRNA and protein levels of LXR, ABCA1, SREBP-1c, ACC-1, and FAS, which are key regulators of lipid biosynthesis and transport; and subsequently reduced cellular lipid levels. Overexpression of the gene encoding SULT2B1b gave similar results as adding exogenous 25HC3S. However, in the absence of 25HC or in the presence of T0901317, synthetic liver oxysterol receptor (LXR) agonist, SULT2B1b overexpression had no effect on the regulation of key genes involved in lipid metabolism.ConclusionsOur data indicate that sulfation of 25HC by SULT2B1b plays an important role in the maintenance of intracellular lipid homeostasis via the LXR/SREBP-1c signaling pathway in HAECs.     

保元强肾Ⅱ号胶囊对慢性肾功能衰竭肾小管间质损伤的临床研究

目的:探讨中药保元强肾Ⅱ号胶囊对慢性肾功能衰竭(CRF)的疗效及机理。方法:60例CRF患者随机分为保元强肾Ⅱ号胶囊加洛汀新组(治疗组,30例)及必需氨基酸加洛汀新组(对照组,30例),观察肾功能及肾小管标志蛋白的改变。结果:治疗组显效率及总有效率分别为633%及933%;对照组分别为300%及567%,治疗组疗效明显优于对照组(P<001);治疗组治疗后BUN、SCr及CCr均较治前明显改善,尿视黄醇结合蛋白、尿β2微球蛋白及尿N乙酰氨基葡萄糖苷酶均比治疗前显著降低,TammHorfau蛋白比治疗前显著增高(P<001或P<005)。结论:保元强肾Ⅱ号胶囊对肾小管间质损伤有明显的改善作用,从而改善肾功能,提高疗效。     

SOME OBSERVATIONS ON THE TREATMENT OF CARDIO-RENAL DISEASF)*

The classification of Bright''s Disease has claimed much attcntion during the present century. Some clinicians content themselves with the simple division into acute and chronic nephritis. This seems hardly adequate when one considers the varying types of the disease which one encounters.     

Preparation and distribution of 5-fluorouracil 125I sodium alginate-bovine serum albumin nanoparticles

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Follow-up care over 12 months of patients with prostate cancer in Spain: A multicenter prospective cohort study

The therapeutic approach is crucial to prostate cancer prognosis. We describe treatments and outcomes for a Spanish cohort of patients with prostate cancer during the first 12 months after diagnosis and identify the factors that influenced the treatment they received.This multicenter prospective cohort study included patients with prostate cancer followed up for 12 months after diagnosis. Treatment was stratified by factors such as hospital, age group (<70 and ≥70 years), and D’Amico cancer risk classification. The outcomes were Eastern Cooperative Oncology Group (ECOG) performance status, adverse events (AEs), and mortality. The patient characteristics associated with the different treatment modalities were analyzed using multivariate logistic regression.We included 470 men from 7 Spanish tertiary hospitals (mean (standard deviation) age 67.8 (7.6) years), 373 (79.4%) of which received treatment (alone or in combination) as follows: surgery (n = 163; 34.7%); radiotherapy (RT) (n = 149; 31.7%); and hormone therapy (HT) (n = 142; 30.2%). The remaining patients (n = 97) were allocated to no treatment, that is, watchful waiting (14.0%) or active surveillance (5.7%). HT was the most frequently administered treatment during follow-up and RT plus HT was the most common therapeutic combination. Surgery was more frequent in patients aged <70, with lower histologic tumor grades, Gleason scores <7, and lower prostate-specific antigen levels; while RT was more frequent in patients aged ≥70 with histologic tumor grade 4, and higher ECOG scores. HT was more frequent in patients aged ≥70, with histologic tumor grades 3 to 4, Gleason score ≥8, ECOG ≥1, and higher prostate-specific antigen levels. The number of fully active patients (ECOG score 0) decreased significantly during follow-up, from 75.3% at diagnosis to 65.1% at 12 months (P < .001); 230 (48.9%) patients had at least 1 AE, and 12 (2.6%) patients died.Surgery or RT were the main curative options. A fifth of the patients received no treatment. Palliative HT was more frequently administered to older patients with higher tumor grades and higher Gleason scores. Close to half of the patients experienced an AE related to their treatment.     

Cystic intracranial lesions: magnetic resonance imaging

Thirty-three patients with cystic intracranial lesions were examined with both magnetic resonance (MR) imaging and CT scanning. The abnormalities imaged included 11 arachnoid cysts, 10 cystic tumors, six postoperative cysts, and three colloid cysts. The intensity patterns of the cyst contents as encoded with routine spin-echo imaging sequences enabled subdivision of the cysts into three categories. Arachnoid and postoperative cysts had an intensity pattern identical to cerebrospinal fluid. More proteinaceous cysts, including inflammatory cysts and nonhemorrhagic tumoral cysts, had an intermediate intensity pattern with characteristically low intensity on the short TR sequence (0.5 sec), but had clearly higher intensity than cerebrospinal fluid on the long TR sequences (2 sec). Finally, three cystic tumors with hemorrhagic fluid and three colloid cysts had a distinctly different pattern of high intensity on all four MR sequences through the same section. MR was superior to CT in characterizing intracranial cystic lesions because of its ability to categorize cysts into these three groups on the basis of the intensity pattern of cyst contents, thereby improving diagnostic specificity and patient management.     

Trends in treatment and overall survival among patients with proximal esophageal cancer

BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT) have been implemented. The trends in(non-)surgical treatment and its impact on overall survival(OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics.RESULTS In total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%,23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval(CI): 6.4-8.1] in 1989-1994 to 9.5 mo(95%CI: 8.1-10.8) in 2010-2014(logrank P 0.001). In non-metastatic disease, 5-year OS rates improved from 5%(95%CI: 3%-7%) in 1989-1994 to 13%(95%CI: 9%-17%) in 2010-2014(logrank P 0.001). Multivariable regression analysis demonstrated a significant treatment effect over time on survival. In metastatic disease, median OS was 3.8 mo(95%CI:2.5-5.1) in 1989-1994, and 5.1 mo(95%CI: 4.3-5.9) in 2010-2014(logrank P = 0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time.     

Temporal trends in primary total hip and knee arthroplasty surgery: results from a UK regional joint register, 1991�C2004

INTRODUCTION

The aim of this study was to evaluate temporal trends in the prevalence of primary total hip and knee replacements (THRs and TKRs) throughout the Trent region from 1991 to 2004.

PATIENTS AND METHODS

The Trent Regional Arthroplasty Study records details of primary THR and TKR prospectively and data from the register were examined. Age and gender population data were provided by the Office for National Statistics.

RESULTS

A total of 26,281 THRs and 23,606 TKRs were recorded during this period. Analysis showed that females had an increased incidence rate ratio (IRR) for both primary THR (IRR = 1.29; 95% CI 1.26–1.33; P < 0.001) and TKR (IRR = 1.17; 95% CI 1.14–1.20; P < 0.001). Patients aged 74–85 years had the largest IRR for both primary THR (IRR = 6.7; 95% CI 6.4–7.0; P < 0.001) and TKR (IRR = 15.3; 95% CI 14.4–16.3; P < 0.001).

CONCLUSIONS

The prevalence of primary TKR increased significantly over time whereas THR remained steady in the Trent region between 1991 and 2004.