Roles of effective stabilizers in improving oral bioavailability of naringenin nanocrystals: Maintenance of supersaturation generated upon dissolution by inhibition of drug dimerization

Nanocrystals (NCs), a colloidal dispersion system formulated with stabilizers, have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs. The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs. However, how stabilizers affect the bioavailability of NCs remains unknown. In this study, F68, F127, HPMC, and PVP were each used as a stabilizer to formulate naringenin NCs. The NCs formulated with PVP exhibited excellent release behaviors, cellular uptake, permeability, oral bioavailability, and anti-inflammatory effects. The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer, which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved. This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.     

Chin-on-Chest in Neck of Femur Fracture (COCNOF) sign: A simple radiographic predictor of frailty and mortality in hip fracture patients

IntroductionFragility fractures are a significant public health challenge often occurring as a result of frailty. Identifying patients who have increased risk of adverse outcomes can aid treating teams in managing these patients appropriately. We hypothesise that the appearance of the patient's head overlapping the lung fields (named Chin on Chest in Neck of Femur sign (COCNOF)) in the admission chest radiograph was a predictor of increased mortality at 3, 6 and 12 months.MethodsAll consecutive patients admitted with hip fracture between 1^st January – 31st December 2019 were analysed. We collected patient characteristics, AMTS score, ASA grade, length of stay, place of discharge, Nottingham Hip Fracture Score, Rockwood Frailty score, Charlson Comorbidity Index and presence of COCNOF sign. The main outcome measures were mortality at 90 days, six months and 12 months following admission.Results469 patients with a mean age of 81.9 (SD 8.4) were included. 18% of patients were COCNOF positive. Univariate analysis showed positive COCNOF sign to be associated with higher mortality at 90 days (19.1 vs 10.8%; RR 1.95, 95%CI 1.05 – 3.63,p=0.03), six months (31.5% vs 14.2%; RR 2.77, 95%CI 1.62 – 4.72, p<0.001) and twelve months (41.6% vs 17.1%; RR 3.45, 95%CI 1.62-4.72, p<0.001). In the multivariate regression models the strongest predictors of mortality were age, gender and CCI it is therefore likely that the COCNOF sign is acting as a surrogate marker of these variables within the univariate models.ConclusionOur results suggest that COCNOF sign is a simple radiographic marker which can be used to identify patients with higher levels of frailty and increased risk of mortality following hip fracture.     

Stereotactic radiofrequency ablation of tumors at the hepatic venous confluence

BackgroundRadiofrequency ablation (RFA) is subject to “heat-sink” effects, particularly for treatment of tumors adjacent to major vessels.MethodsIn this retrospective study, 104 patients with 137 tumors (40 HCC, 10 ICC and 54 metastatic liver tumors) close to (≤1 cm from) the hepatic venous confluence underwent stereotactic RFA (SRFA) between June 2003 and June 2018. Median tumor size was 3.7 cm (1.4–8.5) for HCC, 6.4 cm (0.5–11) for ICC and 3.8 cm (0.5–13) for metastases. Endpoints comprised safety, local tumor control, overall and disease-free survival.ResultsThe overall major complication rate was 16.0% (20/125 ablations), where 8 (40%) were successfully treated by the interventional radiologist in the same anesthetic session and did not prolong hospital stay. 134/137 (97.8%) tumors were successfully ablated at initial SRFA. Local recurrence (LR) developed in 19/137 tumors (13.9%). The median and overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 51.5 months, 73.5%, 67.0%, and 49.7% for HCC, 14.6 months, 60.0%, 32.0% and 32.0% for ICC and 38.1 months, 91.4%, 56.5% and 27.9% for metastatic disease, respectively.ConclusionSRFA represents a viable alternative to hepatic resection for challenging tumors at the hepatic venous confluence.     

ABC goal achievement predicts microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes: The Coronary Artery Calcification in Type 1 Diabetes Study

HypothesisVascular complications of type 1 diabetes are thought to cluster. We examined the prevalence and incidence of vascular complications and American Diabetes Association's ABC goal achievements in a prospective cohort of adults with type 1 diabetes. We hypothesized that ABC achievement at baseline would predict both micro- and macrovascular complications over 6-years.MethodsParticipants (N = 652) were 19–56 year old at baseline and re-examined 6-years later. Microvascular complications included diabetic nephropathy (DN), defined as incident albuminuria (AER ≥ 20 μg/min) or rapid GFR decline (> 3.3%/year) by CKD-EPI cystatin C and proliferative diabetic retinopathy (PDR), defined as laser eye-therapy. Macrovascular complications were defined as coronary artery calcium progression (CACp), measured by electron-beam computed-tomography. ABC goals were defined as HbA1c < 7.0%, BP < 130/80 mmHg and LDL-C < 100 mg/dL.ResultsABC control was suboptimal with only 6% meeting all goals. Meeting no ABC goals at baseline compared to meeting all goals was associated with increased odds of developing microvascular complications (OR: 8.5, 2.3–31.5, p = 0.001), but did not reach significance for CACp (OR: 1.7, 0.8–3.9, p = 0.19).ConclusionABC achievement at baseline strongly predicted microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes, suggesting a need for novel therapeutic targets to complement conventional risk factors in treating macrovascular complications.     

CLINICAL AND DEMOGRAPHIC PREDICTORS OF UNILATERAL SPATIAL NEGLECT RECOVERY AFTER PRISM THERAPY AMONG STROKE SURVIVORS IN THE SUB-ACUTE PHASE OF RECOVERY

Background and AimsUnilateral Spatial Neglect (USN) affects rehabilitation process and leads to poor outcomes after stroke. Intervention for USN treatment has been suggested such as prism therapy (PA). However, factors that influence USN recovery has not been investigated. This study investigated the predictors of USN recovery after prism therapy.MethodsThis study was a single-blinded randomised controlled trial. USN was assessed with the conventional subset of the behavioural inattention test (BIT-C). A total of 74 USN patients who presented with USN following right-brain damage were divided into prism (n = 37) and control (n = 37) groups. Prism group used 20 dioptre prism lenses for repeated aiming, for 12 sessions, the control group used neutral lenses for similar aiming training. Clinical recovery was defined as BIT-C score>129: recovery, BIT-C score< 129: No recovery. Logistic regression was done to establish significant variable in the prediction recovery after PA.ResultsThere were significantly greater improvement of BIT-C in the intervention group post treatment (P≤0.001). Predictor variables considered in this study was cognitive ability (assessed using the mini-mental scale), gender, age, years of education, race, employment status, handedness, type of stroke, site of stroke and site of stroke. Cognitive ability (OR =1.52, CI=1.08-2.14, p= 0.016) was found to significantly influence recovery following PA treatment.ConclusionsThis study highlights the characteristics of stroke patient that will most likely benefit from a PA treatment regimen. Higher cognitive ability was implicated to be a factor for USN recovery after PA treatment post-stroke.     

聚乙二醇修饰牛血红蛋白产物的分离纯化和检测

目的:研究聚乙二醇修饰剂单甲氧基聚乙二醇琥珀酰亚胺酯(SC-mPEG)对牛血红蛋白(BHB)修饰产物的合适的分离纯化、检测方法。方法:采用阳离子交换层析以及有机溶剂沉淀法进行分离,并采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)和三硝基苯磺酸(TNBS)法进行检测。结果:阳离子交换层析法分离出修饰与低修饰产物,TNBS法检测阳离子交换层析分离所得2个峰值产物的平均修饰率分别为52.95%和14.19%。结论:阳离子交换层析法可作为分离纯化SC-mPEG-BHB的方法;TNBS方法可作为检测SC-mPEG-BHB平均修饰率的方法。     

浅谈中国传统文化视阈下的医学生生命观教育

中国传统文化是中华民族共有的精神家园,利用传统文化丰富的生命观资源时医学生进行教育,可以使医学生正确认识生命的价值和意义,懂得敬畏生命、珍惜生命,提高自我的生命质量,树立为拯救生命的神圣事业而奉献终生的伟大理想。