On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet

While the role of collagen and elastin fibrous components in heart valve valvular biomechanics has been extensively investigated, the biomechanical role of the glycosaminoglycan (GAG) gelatinous-like material phase remains unclear. In the present study, we investigated the biomechanical role of GAGs in porcine aortic valve (AV) leaflets under tension utilizing enzymatic removal. Tissue specimens were removed from the belly region of porcine AVs and subsequently treated with either an enzyme solution for GAG removal or a control (buffer with no enzyme) solution. A dual stress level test methodology was used to determine the effects at low and high (physiological) stress levels. In addition, planar biaxial tests were conducted both on-axis (i.e. aligned to the circumferential and radial axes) and at 45° off-axis to induce maximum shear, to explore the effects of augmented fiber rotations on the fiber–fiber interactions. Changes in hysteresis were used as the primary metric of GAG functional assessment. A simulation of the low-force experimental setup was also conducted to clarify the internal stress system and provide viscoelastic model parameters for this loading range. Results indicated that under planar tension the removal of GAGs had no measureable affect extensional mechanical properties (either on- or 45° off-axis), including peak stretch, hysteresis and creep. Interestingly, in the low-force range, hysteresis was markedly reduced, from 35.96 ± 2.65% in control group to 25.00 ± 1.64% (p < 0.001) as a result of GAG removal. Collectively, these results suggest that GAGs do not play a direct role in modulating the time-dependent tensile properties of valvular tissues. Rather, they appear to be strongly connected with fiber–fiber and fiber–matrix interactions at low force levels. Thus, we speculate that GAGs may be important in providing a damping mechanism to reduce leaflet flutter when the leaflet is not under high tensile stress.     

Comparative efficacy of exenatide versus insulin glargine on glycemic control in type 2 diabetes mellitus patients inadequately treated with metformin monotherapy

PurposeComparative efficacy of exenatide versus insulin glargine primarily on glucemic control, and secondarily on body mass index (BMI), lipid profile and blood pressure, in type 2 diabetes mellitus (T2DM) patients suboptimally treated with metformin monotherapy.Material/MethodsForty-seven inadequately treated T2DM patients on metformin assigned to exenatide (n=18) or insulin glargine (n=29) for 26 weeks. Glycosylated hemoglobin (HbA1c), serum lipids, BMI, systolic and diastolic blood pressure, and adverse events, including episodes of hypoglycemia and gastrointestinal symptoms, were recorded.ResultsEither treatment had a similar favorable mean reduction in HbA1c. However, more patients in exenatide group achieved HbA1c ≤ 7% at the 26th week compared with insulin glargine group (p=0.036). Insulin glargine group had significantly more episodes of hypoglycemia compared with exenatide group (p=0.039). Gastrointestinal adverse events were non-significantly higher in the exenatide group. A significantly greater BMI reduction was observed in exenatide group, whereas BMI was not altered in insulin glargine group. Total and LDL cholesterol (p=0.012), and triglycerides (p=0.016) significantly decreased, whereas HDL cholesterol increased (p=0.021) in the exenatide group, whereas only total cholesterol decreased in insulin glargine group. Changes in systolic and diastolic blood pressure were insignificant in both groups.ConclusionsExenatide provided similar reduction in HbA1c, but fewer episodes of hypoglycemia, compared with insulin glargine. Exenatide had also a favorable effect on weight loss, although more gastrointestinal adverse events. Exenatide may provide a justified alternative in second line treatment of T2DM, but more trials are required to elucidate its long-term safety and cost-effectiveness.     

Ⅱ型胶原在T-2毒素诱导大鼠关节软骨早期损伤中的干预作用

目的 观察Ⅱ型胶原在T-2毒素诱导大鼠关节软骨早期损伤中的干预作用,在分子水平上寻找软骨损伤及修复的分子学生物标志,为探讨关节软骨损伤疾病的防治措施提供理论依据.方法 Wistar大鼠80只,按体质量随机分为4组:阴性对照组、阳性对照组、高剂量干预组、低剂量干预组,每组20只.阴性对照组食用常规成品颗粒饲料,其他3组食用含100 ng/kg T-2毒素染毒饲料;阴性对照组和阳性对照组饮自来水;低、高剂量干预组饮用含Ⅱ型胶原0.5、5.0 g/L的自来水.在3、5个月时处死大鼠,光镜下观察大鼠透明软骨的组织病理学改变,用酶联免疫吸附试验(ELISA法)检测大鼠血清Ⅱ型胶原羧基末端肽(CTX-Ⅱ)、软骨寡聚基质蛋白(COMP)及尿中吡啶啉(DPD)含量.结果 光镜下阳性对照组大鼠关节软骨细胞排列紊乱,软骨细胞变形、变性,可见大面积的软骨细胞坏死,而高、低剂量干预组表现为软骨表面原纤维形成,表层软骨细胞肿胀变圆,扁平的软骨细胞减少,软骨细胞簇集等骨关节炎早期病理改变.在3、5个月时,阴性对照组、阳性对照组、高剂量干预组、低剂量干预组大鼠血清CTX-Ⅱ含量分别为(18.77±4.61)、(25.07±9.17),(24.43±5.23)、(39.17±10.49),(21.11±5.02),(33.20±9.74),(19.87±4.53)、(29.73±9.32)μg/L;血清COMP含量分别为(5.43±2.75)、(6.38±2.23),(21.37±4.72)、(24.52±4.26),(17.27±4.77)、(20.32±4.74),(20.13±5.07)、(19.44±4.92)μg/L.其中,3个月时,与阴性对照组比较,阳性对照组血清CTX-Ⅱ含量明显升高(P＜0.05),而低、高剂量干预组未见明显改变(P均＞ 0.05);5个月时,与阴性对照组比较,其他3组血清CTX-Ⅱ含量明显升高(P均＜ 0.05),而高、低剂量干预组明显低于阳性对照组(P均＜0.05).3个月时,与阴性对照组比较,其他3组血清COMP含量明显升高(P均＜0.05),而与阳性对照组比较,高剂量干预组血清COMP含量明显降低(P＜0.05);5个月时,与阴性对照组比较,其他3组血清COMP含量明显升高(P均＜0.05),而与阳性对照组比较,高、低剂量干预组血清COMP含量明显降低(P均＜0.05).3、5个月时,上述4组大鼠尿液DPD含量分别为( 3.47±2.20)、(4.14±1.06),(4.09±2.48)、(4.33±3.43),(3.86±2.31)、(5.72±3.89),(3.58±2.77)、(4.23±2.90)μg/L,组间比较,差异无统计学意义(F值分别为2.608、2.436,P均＞0.05).结论 Ⅱ型胶原能拮抗T-2毒素的软骨损伤作用,延缓关节软骨的破坏进程,降低大鼠血清中CTX-Ⅱ及COMP水平.     

Systematic review of efficacy of dose-dense versus non-dose-dense chemotherapy in breast cancer, non-Hodgkin lymphoma, and non-small cell lung cancer

Randomized controlled trials (RCTs) have suggested a potential advantage of dose-dense chemotherapy in improving disease-free and overall survival in patients with certain malignancies. This systematic review summarizes the literature on the efficacy of dose-dense chemotherapy across various cancers (breast cancer, non-Hodgkin lymphoma [NHL], and non-small cell lung cancer) and chemotherapy regimens. Among the 17 trials identified, few reported statistically significant differences between dose-dense and standard chemotherapy, and most were small with limited statistical power. Statistically significant differences in overall survival favoring dose-dense schedules were apparent among large RCTs in potentially curative settings such as early-stage breast cancer and NHL. Clinical and treatment heterogeneity demonstrated the flexibility of the dose-dense paradigm but also precluded quantitative meta-analysis of results. Further study of dose-dense schedules based on large RCTs is needed to demonstrate the consistency and generalizability of these findings.     

白花蛇舌草-半枝莲药对组分对结肠腺癌Lovo细胞生物学行为的影响

摘要:目的　探讨白花蛇舌草-半枝莲药对组分对结肠腺癌Lovo细胞增殖、侵袭、迁移和凋亡的影响及作用机制。方法　将白花蛇舌草、半枝莲按质量1∶1进行3次煎煮,获得水提物,后取适量浸膏用石油醚回流脱脂,再以乙酸乙酯进行多次萃取,获得白花蛇舌草-半枝莲药对组分,并计算得率。实验分为对照组（正常培养Lovo细胞）、白花蛇舌草-半枝莲药对组分低剂量组（10 mg/L）、中剂量组（30 mg/L）及高剂量组（50 mg/L）。通过噻唑蓝比色法（MTT）检测各组细胞培养24、48、72 h后的增殖抑制率。各组细胞培养48 h后,流式细胞仪检测细胞周期分布;Transwell实验检测细胞侵袭能力;划痕实验检测细胞迁移能力;TUNEL法检测细胞凋亡情况;Western blot法检测Grb2相关结合蛋白1（Gab1）、血管内皮生长因子受体2（VEGFR-2）、磷脂酰肌醇3-激酶（PI3K）、苏氨酸激酶（Akt）、基质金属蛋白酶-9（MMP-9）、B淋巴细胞瘤-2基因（Bcl-2）、Bcl-2相关X蛋白（Bax）蛋白表达情况。结果　化学萃取后的白花蛇舌草-半枝莲药对中主要含有对羟基苯乙酮、野黄芩苷、木犀草素和芹菜素4种化合物,组分得率为0.61%。与对照组相比,低、中、高剂量组细胞增殖抑制率升高,G1期肿瘤细胞比例增加,细胞凋亡指数增高,侵袭细胞数和划痕闭合率明显减小（均P＜0.05）,细胞中Gab1、VEGFR-2、PI3K、Akt、MMP-9、Bcl-2蛋白表达降低,Bax表达升高（均P＜0.05）,且存在剂量依赖性。结论　白花蛇舌草-半枝莲药对组分可抑制结肠腺癌Lovo细胞的增殖,降低其迁移和侵袭能力,诱导细胞凋亡,其机制可能与抑制Gab1/VEGFR-2/PI3K/Akt信号通路活化有关。     

The floating cardiac fat pad—sign of occult pneumothorax

Pneumothoraces are a possible sequela of chest trauma with potential morbidity and mortality if not recognized and treated promptly. A portable supine chest radiograph is frequently the first radiologic study performed in the setting of trauma. While large pneumothoraces can be readily recognized on these radiographs, smaller pneumothoraces are missed in up to 15 % of trauma patients. There are many radiographic signs of occult pneumothoraces, and we are presenting a new radiographic sign of occult pneumothorax. The floating cardiac fat pad sign occurs when pleural air collects anteriorly and superiorly in the most non-dependent portion of the chest lifting the pericardial fat pad off the diaphragm. Lung markings are still seen surrounding the pericardial fat pad due to the inflated lower lobe of the lung resting dependently. Rapid and accurate identification of pneumothoraces is critical but often difficult on chest radiographs. Although there are many existing radiographic signs for identification of pneumothorax, prospective identification of small pneumothoraces is still relatively poor. Here, we describe an additional sign which aides in the detection of pneumothoraces, the floating cardiac fat pad. When present, this should prompt further evaluation with chest CT or upright chest radiograph.     

Corpora amylacea in a leiomyoma of soft tissue

A case of myxoid leiomyoma of deep soft tissue is described. The patient was a 42-year-old woman who presented with menorrhagia, and an ischiorectal mass was identified. A total hysterectomy was performed, and the mass was removed. On gross examination, the mass was 6cm x 5cm x 4cm and had a mucoid cut surface. Histologic examination revealed a myxoid leiomyoma with abundant intracellular corpora amylacea (CA). An infarcted leiomyoma was present in the hysterectomy specimen. The patient remains well, with no evidence of recurrence 3 years after surgery. Leiomyomas of deep soft tissue are rare, and, to our knowledge, none have been described containing CA.