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Furthermore, the potential for supercritical fluid technology to overcome the shortcomings associated with conventional drug formulation methods is reviewed.BACKGROUND Oxaliplatin, used as first-choice treatment for colorectal cancer (CRC), induces sinusoidal endothelial injury and portal hypertension. This study investigated the characteristics of oxaliplatin-induced portal hypertension and evaluated the efficacy of endoscopic management of gastroesophageal variceal bleeding. METHODS We performed a retrospective, multicenter, case-control study between January 2010 and December 2018. Patients who received oxaliplatin-based chemotherapy after CRC surgery and presented with portal hypertension and gastroesophageal varices were compared with consecutive patients with hepatitis B-related cirrhotic portal hypertension receiving endoscopic treatment for variceal bleeding. RESULTS 39 patients with oxaliplatin-induced portal hypertension were identified, 35 of whom had a history of variceal bleeding. The median period between start of oxaliplatin-based chemotherapy and the occurrence of varices was 50.4 months (n = 39). A total of 26 patients with oxaliplatin-related portal hypertension and 230 patients with hepatitis B-related portal hypertension underwent endoscopic treatment. Kaplan-Meier analysis revealed that the 1-year rebleeding rate was significantly higher in the oxaliplatin group than in the hepatitis B group (43.3 % vs. 19.0 %, P = 0.001). Multivariable Cox regression analysis showed that oxaliplatin-based chemotherapy was an independent factor for 3-year rebleeding (hazard ratio [HR] 2.46, 95 % confidence interval [CI] 1.24-4.87; P = 0.01) and 3-year overall mortality (HR 9.43, 95 %CI 2.32-38.31; P = 0.002). CONCLUSIONS Oxaliplatin-related portal hypertension was characterized by massive ascites, splenomegaly, gastric varices, concomitant arterioportal fistula, and relatively normal liver function. Endoscopic treatment to prevent variceal rebleeding in these patients was unsatisfactory compared with endoscopic treatment for hepatitis B-related portal hypertension.Clinical studies revealed that some aged-individuals accumulate a significant number of histopathological Alzheimer´s disease (AD) lesions in their brain, yet without developing any signs of dementia. Animal models of AD represent suitable tools to identify genes that might promote cognitive resilience and hence, this study first set out to identify cognitively resilient individuals in the aged-Tg2576 mouse model. A transcriptomic analysis of these mice identified PLA2G4E as a gene that might confer resistance to dementia. Indeed, a significant decrease in PLA2G4E is evident in the brain of late-stage AD patients, whereas no such changes are observed in early stage patients with AD neuropathological lesions but no signs of dementia. We demonstrated that adeno-associated viral vector-mediated overexpression of PLA2G4E in hippocampal neurons completely restored cognitive deficits in elderly APP/PS1 mice, without affecting the amyloid or tau pathology. These PLA2G4E overexpressing APP/PS1 mice developed significantly more dendritic spines than sham-injected mice, coinciding with the cognitive improvement observed. Hence, these results support the idea that a loss of PLA2G4E might play a key role in the onset of dementia in AD, highlighting the potential of PLA2G4E overexpression as a novel therapeutic strategy to manage AD and other disorders that course with memory deficits.The problem with high sBP combined with low dBP requires attention because sBP is directly and continuously related to the most important criterion - all-cause mortality - whereas dBP becomes inversely related to it after the age of 50-60 years. The 2018 European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) guidelines for hypertension (HTN) are very helpful to recommend a lower level of safety of in-treatment dBP. https://www.selleckchem.com/products/gdc-0068.html To prevent tissue hypoperfusion, HTN guidelines recommend that dBP should be ≥70 mmHg on-treatment. A patient with very elevated sBP (e.g., 220 mmHg) and low dBP (e.g., 65 mmHg) is difficult to treat if one strictly follows the guidelines. In this situation, sBP is a clear indication for antihypertensive treatment, but a relative contraindication is dBP (being lower than 70 mmHg, a recognized safety border by 2018 ESC/ESH guidelines). The dilemma about whether to treat (isolated) systolic hypertension ((I)SH) patients with low dBP ( less then 70 mmHg) or not is evident by the fact that almost half of them (45%) remain untreated. This is a common occurrence and identifying this problem is the first step to solving it. We suggest that an adequate search and analyses ought to be performed to solve this issue, starting from the exploration of prognosis of (I)SH subset with too low dBP ( less then 70 mmHg) at the beginning of already performed randomized clinical trials.Background Previous studies have reported on several genetic variants related to breast cancer, but a substantial proportion of mutation loci have not yet been identified. In the current study, we aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of interleukin-10 (IL-10) and susceptibility to breast cancer in Shaanxi Han women in China. Methods Six SNPs were genotyped in 530 breast cancer patients and 628 healthy women from the First Affiliated Hospital of Xi'an Jiaotong University Hospital. Odds ratios and 95% confidence intervals were calculated by unconditional logistic regression analysis to assess the association between breast cancer risk and polymorphisms of six loci. Results Two SNPs, rs3024490 and rs1800871, were found to be significantly different between breast cancer patients and healthy women. These SNPs also increased the risk of breast cancer in co-dominant and dominant models. Moreover, another SNP, rs1554286, was significantly associated with an increased risk of breast cancer in the co-dominant model. Functional assessments indicated that these three variants may influence the expression and transcription factor binding of IL-10. Conclusions Our findings suggest that variants of IL-10 may be likelihood risk factors for the development and progression of breast cancer. Future studies should replicate this study and evaluate functional assessments in Chinese Han women and women from other regions.
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