Hsa-miR-4282对肝癌细胞系SMMC-7721生长的影响

目的  探讨Hsa-miR-4282在肝癌细胞系SMMC-7721中的表达及其对细胞生长的影响。方法 采用实时荧光定量PCR法检测Hsa-miR-4282在人正常肝上皮细胞系HL-7702和人肝癌细胞系MHCC97-H、SMMC-7721，以及 20例肝癌组织及其相应癌旁组织中的表达。采用瞬时转染法将Hsa-miR-4282 mimics（上调组）和Hsa-miR-4282 inhibitor（下调组）分别转染肝癌SMMC-7721细胞，上调组和下调组分别设置相应阴性对照组。转染后采用MTT法检测细胞增殖能力，平板克隆形成实验检测细胞克隆形成能力，流式细胞仪检测细胞凋亡能力。结果 Hsa-miR-4282在肝癌组织、肝癌细胞MHCC97-H及肝癌细胞SMMC-7721中的表达均低于癌旁组织及正常肝细胞HL-7702（P＜0.05）。MTT实验结果显示，Hsa-miR-4282上调后肝癌SMMC-7721细胞的OD值低于其阴性对照组，而下调后OD值高于其阴性对照组 （P＜0.05）。平板克隆形成实验显示，下调组的细胞克隆数高于其阴性对照组［（240±7） 个 vs （191±10） 个，P=0.005）］，而上调组细胞克隆数低于基阴性对照组［（146±10） 个 vs （193±12） 个，P=0.013）］。流式细胞仪检测结果显示，Hsa-miR-4282上调组细胞凋亡率较其阴性对照组升高［（23.89±1.89）% vs（16.6±1.14）%，P=0.009）］，下调组细胞凋亡率较期阴性对照组降低［（14.98±0.46）% vs （17.79±0.73）%，P=0.010］。结论 Hsa-miR-4282上调可抑制肝癌SMMC-7721细胞增殖，促进细胞凋亡，可能与肝癌的发病机制有关。     

Ethyl lactate as a potential green solvent to extract hydrophilic (polar) and lipophilic (non-polar) phytonutrients simultaneously from fruit and vegetable by-products

Phytonutrients extracted from natural resources are receiving much attention among researchers due to their highly antioxidative characteristics which prevent several degenerative diseases including cardiovascular diseases and cancers. These nutraceutical compounds can be used in food, pharmaceutical and cosmetic products as natural antioxidants, preservatives, colourants and functional foods. Huge volume of food wastes are generated from the processing industry and these low-value food residues are rich in various phytonutrients worth recovering. This approach of valorisation reduces the generation of food wastes and is cost-effective considering the cheap feedstock, reduced waste management expenses and high market value of extracted compounds. In light of the health and safety risks posed by commonly used organic extraction solvents derived from the petrochemical industry, there is a need to recover the phytonutrients using green, sustainable and efficient solvents that are safe for human consumption. This work discusses ethyl lactate as a safe, green, efficient and potentially cheap solvent to recover phytonutrients from fruit and vegetable by-products. Ethyl lactate is compared with other organic solvents commonly used from the aspects of safety, environmental impacts and efficiency. Current challenges when employing ethyl lactate are also discussed.     

Emerging from their burrow: Hedgehog pathway inhibitors for cancer

Introduction: Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and its constitutive activation is tumorigenic in basal cell carcinoma (BCC). The HhP enables phenotypic flexibility, and channels tumor-stroma interactions. As a result, it is over-expressed in numerous cancers as well as in the tumor microenvironment and may represent a promising therapeutic target.

Areas covered: In this article, we review the rationale for targeting HhP and its role as an oncogenic driver, in tumor epithelial-to-mesenchymal transition (EMT), and in the tumor microenvironment and describe the results of preclinical and clinical studies involving HhP inhibitors.

Expert opinion: HhP activation plays an important role in both the tumor microenvironment and tumor EMT which can lead to treatment resistance for a number of different malignancies. In addition to standard use in BCC, several HhP inhibitors are in preclinical, early, and mid-stage clinical development for other solid and hematologic malignancies.     

Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study

ABSTRACT

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.

Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).

Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61–3.18), coagulation disorders (aOR 1.81, 95% CI 1.43–2.30), and decreased PLT (aOR 1.46, 95% CI 1.25–1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79–1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11–2.10), coagulation disorders (aOR 1.53, 95% CI 1.21–1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81–1.07) or bleeding (aOR 1.11, 95% CI 0.87–1.42), compared with those receiving cefoperazone-tazobactam.

Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.     

2005年样本医院使用主要抗肿瘤药之分析

据悉,国家发改委已经将《药品定价方法》意见征求稿(初稿)下发各制药行业协会,这是发改委在行政干预药品价格历程中第一个比较全面的政府药价管理指导性文件。纳入政府定价范围的2400个药品品种的定价将遵循这一原则。又有报道,新的药品降价政策将于2006年上半年出台。这次降价     

NT-proBNP reflects right ventricular structure and function in pulmonary hypertension.

The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function.     

犬MC1R基因多态性的研究

目的 利用PCR—RFLP和PCR—SSCP技术分别检测犬MC1R基因中两个序列T105A和R306Ter的基因多态性，为遗传育种、培育出更加优良的实验用犬奠定基础。方法 以224只犬为实验材料，对犬MC1R基因T105A片段和R306Ter片段分别进行PCR-RFLP和PCR—SSCP分析，并且分别对具有RFLP和SSCP多态性的片段进行克隆测序，找出等位基因的差异位点。结果 经对犬MClR基因的PCR-RFLP分析，发现犬MC1R基因的T105A序列具有多态性，表现为三种基因型：AA、AB和BB。通过对具有RFLP多态性的片段进行克隆测序发现MC1R基因在编码第105位氨基酸的密码子处存在由G到A的单碱基突变，该突变导致第105位氨基酸发生由精氨酸向苏氨酸的改变，此外在第207位氨基酸的密码子处还发现由A到G的单碱基突变，并产生了一个HhαI限制性内切酶位点。同时，经过犬MC1R基因的PCR—SSCP分析，发现犬MC1R基因的R306Ter序列具有多态性，表现为三种基因型：CC、CD、DD.通过对具有SSCP多态性的片段进行了克隆测序发现，MC1R基因在编码第306位氨基酸的密码子处存在一个由CGA到TGA的终止突变，而使翻译终止。结论 利用PCR—RFLP和PCR—SSCP分析技术证实犬MC1R基因具有明显的多态性。     

手术治疗跟骨塌陷性骨折

目的　评估跟骨塌陷性骨折手术治疗的效果。方法　 1996年 5月～ 2 0 0 0年 6月共手术治疗跟骨塌陷性骨折 15例 ,8例内固定 ,7例植骨 ,平均随访 14个月 ,参照AOFAS评分对患者有否疼痛、步态、距下关节活动 ,是否支架辅助、术后X线照片等加以评估。结果　两组结果无明显差异。 2例手术切口皮缘坏死 ,6例疗效为优 ,9例为良。结论　跟骨塌陷性骨折手术解剖复位能取得好的效果     

Laparoscopic Local Resection Based on Sentinel Node Evaluation for Early Gastric Cancer: A Preliminary Report

We previously reported that lymphatic mapping using isosulfan blue can be used to identify sentinel nodes (SNs). This study was undertaken to evaluate the feasibility of using the SN technique in treating early gastric cancer and to explore its usefulness for minimal invasive surgery. Twenty-three patients with early gastric cancer who underwent SN biopsy were retrospectively evaluated. Based on SN evaluation, individualized surgery was performed in five patients with T1N0M0 gastric cancer. When pathological examination of frozen sections revealed metastasis in SNs, we performed a standard D2 gastrectomy. Laparoscopic local resection was applied when the SN biopsy was negative. Our results showed that the success rate with SN biopsy in early gastric cancer was 100%, as were the accuracy, sensitivity, and specificity. All five patients with early gastric cancer had SNs negative for metastases both by frozen section and by postoperative pathology. Thus, all these patients underwent laparoscopic local resection without extended lymphadenectomy. We conclude that SN biopsy is a useful tool to individualize the operative procedure, and laparoscopic local resection can be safely performed using SN guidance in selected patients with early gastric cancer.