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.     

MELD-XI Scores Correlate with Post-Fontan Hepatic Biopsy Fibrosis Scores

We tested the hypothesis that MELD-XI values correlated with hepatic total fibrosis scores obtained in 70 predominately stable, post-Fontan patients that underwent elective cardiac catheterization. We found a statistically significant correlation between MELD-XI values and total fibrosis scores (p = 0.003). Thus, serial MELD-XI values may be an additional useful clinical parameter for follow-up care in post-Fontan patients.     

Suppressor of cytokine signaling in allergic inflammation

The immunopathological hallmark of allergic diseases is elevated total and allergen specific serum IgE levels along with inflammation. This inflammation results from the activation of a cadre of hematopoietic and nonhematopoetic cells. This coordinated activation is the result of the increased production of a variety of soluble factors including chemokines and cytokines. The magnitude and the duration of cytokine action will determine the response to an allergen, either mounting a low-grade immunologic response or resulting in exaggerated reaction such as asthma or atopic dermatitis. Thus, the action of cytokines is tightly regulated both developmentally and within the cell. The suppressor of cytokine signaling (SOCS) protein family represents a novel group of cytoplasmic negative feedback regulators of type I and II cytokines. Several of the signaling pathways regulated by SOCS proteins are important in allergic immune responses. Thus, SOCS proteins may be important regulators of atopy.     

Strong association between smoking and the risk of revision in a cohort study of patients with metal‐on‐metal total hip arthroplasty

Thus far the ability to predict who will develop early failure following the insertion of a metal‐on‐metal (MoM) bearing has been very limited. Our objective was to assess the effect of smoking on failure rates in patients with MoM bearing, compared with patients with ceramic‐on‐polyethylene (CoP) bearing. From a prospective hospital‐based registry we included all primary THAs operated upon between 1/2001 and 12/2011 with MoM or CoP bearings of the same cup design and head size (28 mm). We compared revision rates through 10/2013 classified by smoking status and type of bearing. We included 1,964 patients (median age 71, 57% women), 663 with MoM and 1,301 with CoP bearing. Mean follow‐up was 6.9 years (range 1.8–12.8). Revisions were required for 56 THAs. In patients with MoM bearing the adjusted incidence rate of revision among ever‐smokers was four times greater than among never‐smokers (95% CI 1.4–10.9). Among those with CoP bearing, the rate ratio was only 1.3 (95% CI 0.6–2.5). We found a strong association between smoking and increased failure of MoM THAs. In contrast, the association was weak for patients with CoP bearing. Smoking might be a trigger or an effect amplifier for adverse reactions to metal debris from MoM bearings. © 2014 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 32:762–768, 2014.     

Meta-analysis of retrojugular versus antejugular approach for carotid endarterectomy

Introduction

The retrojugular approach for carotid endarterectomy (CEA) has been reported to have the advantages of shorter operative time and ease of dissection, especially in high carotid lesions. Controversial opinion exists with regard to its safety and benefits over the conventional antejugular approach.

Methods

A systematic review of electronic information sources was conducted to identify studies comparing outcomes of CEA performed with the retrojugular and antejugular approach. Synthesis of summary statistics was undertaken and fixed or random effects models were applied to combine outcome data.

Findings

A total of 6 studies reporting on a total of 740 CEAs (retrojugular approach: 333 patients; antejugular approach: 407 patients) entered our meta-analysis models. The retrojugular approach was found to be associated with a higher incidence of laryngeal nerve damage (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 1.46–7.07). No significant differences in the incidence of hypoglossal or accessory nerve damage were identified between the retrojugular and antejugular approach groups (OR: 1.09 and 11.51, 95% CI: 0.31–3.80 and 0.59–225.43). Cranial nerve damage persisting during the follow-up period was similar between the groups (OR: 2.96, 95% CI: 0.79–11.13). Perioperative stroke and mortality rates did not differ in patients treated with the retrojugular or antejugular approach (OR: 1.26 and 1.28, 95% CI: 0.31–5.21 and 0.25–6.50).

Conclusions

Currently, there is no conclusive evidence to favour one approach over the other. Proof from a well designed randomised trial would help determine the role and benefits of the retrojugular approach in CEA.     

In Vitro Comparison of Two Different Mechanical Circulatory Support Devices Installed in Series and in Parallel

This study investigates the novel approach of placing a ventricular assist pump in the descending aorta in series configuration with the heart and compares it with the two traditional approaches of left‐ventricle‐to‐ascending‐aorta (LV‐AA) and left‐ventricle‐to‐descending‐aorta (LV‐DA) placement in parallel with the heart. Experiments were conducted by using the in‐house simulator of the cardiovascular blood‐flow loop (SCVL). The results indicate that the use of the LV‐AA in‐parallel configuration leads to a significant improvement in the systemic and pulmonic flow as the level of continuous flow is increased; however, this approach is considered highly invasive. The use of the LV‐DA in‐parallel configuration leads to an improvement in the systemic and pulmonic flow at lower levels of continuous flow but at higher levels of pump support leads to retrograde flow. In both in‐parallel configurations, increasing the level of pump continuous flow leads to a decrease in pulsatility to a certain extent. The results of placing the pump in the descending aorta in series configuration show that the pressure drop upstream of the pump facilitates cardiac output as a result of afterload reduction. In addition, the pressure rise downstream of the pump may assist with renal perfusion. However, at the same time, the pressure drop generated at the proximal part of the descending aorta induces a slight drop in carotid perfusion, which would be autoregulated by the brain in a native cardiovascular system. The pulse wave analysis shows that placing the pump in the descending aorta leads to improved pulsatility in comparison with the traditional in‐parallel configurations.     

Enzymatic phosphorylation of muscle glycogen synthase: a mechanism for maintenance of metabolic homeostasis.

We recently analyzed experimental studies of mammalian muscle glycogen synthesis using metabolic control analysis and concluded that glycogen synthase (GSase) does not control the glycogenic flux but rather adapts to the flux which is controlled bv the activity of the proximal glucose transport and hexokinase steps. This model did not provide a role for the well established relationship between GSase fractional activity, determined by covalent phosphorylation, and the rate of glycogen synthesis. Here we propose that the phosphorylation of GSase, which alters the sensitivity to allosteric activation by glucose 6-phosphate (G6P), is a mechanism for controlling the concentration of G6P instead of controlling the flux. When the muscle cell is exposed to conditions which favor glycogen synthesis such as high plasma insulin and glucose concentrations the fractional activity of GSase is increased in coordination with increases in the activity of glucose transport and hexokinase. This increase in GSase fractional activity helps to maintain G6P homeostasis by reducing the G6P concentration required to activate GSase allosterically to match the flux determined by the proximal reactions. This role for covalent phosphorylation also provides a novel solution to the Kacser and Acarenza paradigm which requires coordinated activity changes of the enzymes proximal and distal to a shared intermediate, to avoid unwanted flux changes.