LHRHa靶向紫杉醇脂质体的制备及体外抗肿瘤作用

目的:制备促黄体激素释放激素类似物(Luteinizing hormone-releasing hormone analogues,LHRHa)靶向紫杉醇脂质体(Paclitaxel liposomes,PTX-Lipo),研究其在体外增强紫杉醇(Paclitaxel,PTX)对卵巢癌A2780/DDP细胞的抑制作用。方法:采用薄膜超声法制备PTX-Lipo与LHRHa靶向紫杉醇脂质体(LHRHa-Paclitaxel liposomes,LHRHa-PTX-Lipo),用透射电镜考察脂质体形态;高效液相色谱法测定2种PTX-Lipo的包封率;激光共聚焦法通过卵巢癌A2780/DDP细胞对4-氟-7-硝基-2,1,3-苯并氧杂恶二唑荧光素的摄取检测来反映细胞对NBD-Lipo与NBD-LHRHa-Lipo的摄取情况;MTT法及细胞克隆形成实验检测LHRHa-PTX-Lipo体外对卵巢癌细胞的生长抑制情况。结果:制备LHRHa-PTX-Lipo的平均粒径123.4 nm,包封率在90%以上;A2780/DDP细胞对NBD-LHRHa-Lipo组的荧光摄取明显高于NBD-Lipo组;LHRHa-PTX-Lipo对A2780/DDP细胞的生长及克隆形成抑制明显高于PTX组及PTX-Lipo组(P<0.05)。结论:采用薄膜超声法制备的LHRHa-PTX-Lipo可使药物在靶部位聚集,增强药物对卵巢癌细胞的抑制作用。     

Biomechanical Study of Intramedullary Versus Extramedullary Implants for Four Types of Subtrochanteric Femoral Fracture

ObjectivesTo compare the biomechanical performance of proximal femoral nail anti‐rotation (PFNA), the “upside‐down” less invasive plating system (LISS), and proximal femoral locking plate (PFLP) in fixing different fracture models of subtrochanteric fractures.MethodsThirty composite femurs were divided into three equal groups (PFNA, PFLP, and reverse LISS). The implant‐femur constructs were tested under axial compression load (0–1400 N) from models I to IV, which represented the Seinsheimer type I subtrochanteric fracture, type IIIa subtrochanteric fracture with the posteromedial fragment reduced; type IIIa subtrochanteric fracture with the posteromedial fragment lost; and type IV subtrochanteric fracture, respectively. Axial stiffness was analyzed for each group. Each group was then divided into two subgroups, one of which underwent torsional and axial compression failure testing, while the other subgroup underwent axial compression fatigue testing. The torsional stiffness, failure load, and cycles to failure were analyzed.ResultsPFNA had the highest axial stiffness (F = 761.265, p < 0.0001) and failure load (F = 48.801, p < 0.0001) in model IV. The axial stiffness and failure load of the PFLP were significantly higher than those of the LISS (p < 0.0001, p = 0.001). However, no significant difference in axial stiffness was found between models I to III (model I: F = 2.439, p = 0.106; model II: F = 2.745, p = 0.082; model III: F = 0.852, p = 0.438) or torsional stiffness in model IV (F = 1.784, p = 0.187). In fatigue testing, PFNA did not suffer from construct failure after 90,000 cycles of axial compression. PFLP and LISS were damaged within 14,000 cycles, although LISS withstood more cycles than PFLP (t = 3.328, p = 0.01).ConclusionThe axial stiffness of the three implants was similar in models I to III. The biomechanical properties of PFNA were the best of the three implants in terms of axial stiffness, failure load, and fatigue testing cycles in model IV. The axial stiffness and failure load of the PFLP were better than those of the reverse LISS, but PFLP had fewer cycles in the fatigue tests than the reverse LISS.     

A systematic review of the efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia

Background:Vascular dementia (VaD) is a comprehensive syndrome related to the damage of cognitive function and various cerebral vascular illnesses. VaD is also generally recognized as the second most common type of dementia after Alzheimer disease, contributing to 30% of the dementia population in Asia and developing countries. The ability of donepezil hydrochloride and nimodipine had been respectively proven in improving cognitive function in vascular dementia. However, whether the combined application of both drugs contribute to better efficacy remains as a research hotspot. Studies had shown definite satisfactory result with such combination, however evidence-based evaluation of the efficacy is still lacking. Therefore, meta-analysis is employed in this study to evaluate the efficacy and safety of using donepezil hydrochloride combined with nimodipine in treating VaD to provide references for clinical treatments. The efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia is systematically reviewed to provide evidence-based references for clinical applications.Methods:Both Chinese and English databases were searched from the start till August, 2020 for any RCT regarding the combined use of the 2 drugs in treating vascular dementia. Two investigators would later evaluate and screened out research and data based on an improved Jaded scale. Software Rev Man 5.3.0 was employed to carry out meta-analysis on clinical effificacy, mini-mental state examination (MMSE) ratings, activity of daily living (ADL) ratings, and clinical dementia scale (CDR) ratings.Results:Donepezil hydrochloride combined with nimodipine had demonstrated satisfactory efficacy on the treatment of vascular dementia. Improvements were namely spotted on MMSE scale, ADL scale, and CDR scale, with the utmost efficacy by 12 weeks after intervention.Conclusions:Donepezil hydrochloride combined with nimodipine had good efficacy in the treatment of patients with vascular dementia, mainly in terms of improving the Simple MMSE scores, the ability to use daily living scale (ADL) scores and the CDR, and the best results were obtained after 12 weeks of intervention. Such conclusion should be cautiously evaluated.     

真皮导管瘤一例

患者男,61岁,因头枕部丘疹3年就诊。患者于3年前无明显诱因下发现枕部丘疹,无自觉症状,后缓慢增大。否认病程中出血、溃疡、脱屑等。体检：一般情况好,各系统检查未见异常。皮肤科检查：枕部见一枚黄豆大小丘疹,直径约9 mm,淡红色,境界清晰,表面光滑,质地坚实（图1A）……     

Differential Associations of Intakes of Whole Grains and Coarse Grains with Risks of Cardiometabolic Factors among Adults in China

There is a lack of studies on the association between whole grain intake and cardiometabolic risk factors in China and the current definition of whole grains is inconsistent. This study defined whole grains in two ways, Western versus traditional, and examined their associations with the risks of major cardiometabolic factors (CMFs) among 4706 Chinese adults aged ≥18 years, who participated in surveys both in 2011 and in 2015. Diet data were collected by consecutive 3 d 24 h recalls, together with household seasoning weighing. Whole grains were defined as grains with a ratio of fiber to carbohydrate of ≥0.1, while coarse grains were defined as grains except for rice and its products, and wheat and its products. Multivariable logistic regressions were modeled to analyze the associations of intakes of whole grains and coarse grains, respectively, with risks of major CMFs including obesity-, blood pressure-, blood glucose- and lipid-related factors, which were defined by International Diabetes Federation and AHA/NHLBI criteria. After adjusting for potential confounders, the odds of elevated LDL-C decreased with the increasing intake levels of whole grains (OR 0.64, 95% CI 0.46–0.88, p-trend < 0.05). Moreover, adults with the whole grain intake of 50.00 to 150.00 g/day had 27% lower odds of overweight and obesity (OR 0.73, 95% CI 0.54–0.99) and 31% lower odds of elevated LDL-C (OR 0.69, 95% CI 0.49–0.96), as compared with non-consumers. In conclusion, given the significant nutrient profiles of whole grains and coarse grains, the adults with higher intakes of whole grains only may have a lower risk of LDL-C and overweight and obesity.     

PRRSV Induces HMGB1 Phosphorylation at Threonine-51 Residue to Enhance Its Secretion

Porcine reproductive and respiratory syndrome virus (PRRSV) induces secretion of high mobility group box 1 (HMGB1) to mediate inflammatory response that is involved in the pulmonary injury of infected pigs. Our previous study indicates that protein kinase C-delta (PKC-delta) is essential for HMGB1 secretion in PRRSV-infected cells. However, the underlying mechanism in HMGB1 secretion induced by PRRSV infection is still unclear. Here, we discovered that the phosphorylation level of HMGB1 in threonine residues increased in PRRSV-infected cells. A site-directed mutagenesis study showed that HMGB1 phosphorylation at threonine-51 was associated with HMGB1 secretion induced by PRRSV infection. Co-immunoprecipitation (co-IP) of HMGB1 failed to precipitate PKC-delta, but interestingly, mass spectrometry analysis of the HMGB1 co-IP product showed that PRRSV infection enhanced HMGB1 binding to ribosomal protein S3 (RPS3), which has various extra-ribosomal functions. The silencing of RPS3 by siRNA blocked HMGB1 secretion induced by PRRSV infection. Moreover, the phosphorylation of HMGB1 at threonine-51 was correlated with the interaction between HMGB1 and RPS3. In vivo, PRRSV infection also increased RPS3 levels and nuclear accumulation in pulmonary alveolar macrophages. These results demonstrate that PRRSV may induce HMGB1 phosphorylation at threonine-51 and increase its interaction with RPS3 to enhance HMGB1 secretion. This finding provides insights into the pathogenesis of PRRSV infection.     

心力衰竭对门静脉频谱形态的影响

目的探讨心力衰竭对门静脉频谱形态的影响,摸索超声检查评价心功能的新途径。方法选取临床Ⅰ～Ⅲ度心力衰竭患者60例,按心衰竭程度分组,每组各20例;健康对照组20例。排除肝脏及门静脉、下腔静脉病变。经右侧肋间及剑突下探查门静脉,在取得门静脉清晰二维切面图像后,记录1～3个呼吸周期中的门静脉频谱,观察频谱形态,记录各组不同门静脉频谱形态的例数,所获资料采用统计软件SPSS11.0处理。结果健康对照组门静脉频谱均表现为单向连续频谱,各心力衰竭组出现不同程度的门静脉收缩末期反向血流,Ⅲ度心力衰竭组门静脉频谱多出现恒定的收缩末期反向血流。结论心力衰竭可导致门静脉频谱形态异常,观察门静脉频谱形态,可作为判断心力衰竭程度的辅助依据。     

慢性阻塞性肺疾病急性加重期炎性细胞因子与肺功能的相关性

目的 分析慢性阻塞性肺疾病急性加重期炎性细胞因子水平变化及与肺功能的相关性.方法 对本院2019年3月—2020年3月收治的62例患者的炎性细胞因子进行检测,分析各项炎性细胞因子水平变化情况及其与患者肺功能之间的相关性.结果 62例患者的IL-6指标、IL-8指标和TNF-α指标均随着患者综合评估分级的增加而增加,且各...     

利妥昔单抗治疗难治性激素耐药型肾病综合征的疗效和安全性

目的:探讨利妥昔单抗(RTX)治疗儿童难治性激素耐药型肾病综合征(SRNS)的疗效和安全性。方法:回顾性分析2013年9月至2018年3月东部战区总医院儿科收治并接受RTX治疗的10例难治性SRNS患儿的临床资料。结果:10例患儿发病年龄(4.47±2.75)岁,男女各5例;5例(50%)肾活检为局灶节段性肾小球肾炎,...