毛细管电色谱的研究进展及其在药物分析中的应用

目的：毛细管电色谱在药物分析中的应用研究。方法：结合国内外有关毛细管电色谱的文献资料,综述毛细管电色谱的研究进展、毛细管电色谱整体柱制备新进展及其在药物分析中的应用。结果：毛细管点色谱在分析领域已得到广泛良好的应用。结论：毛细管电色谱拥有广阔的应用前景。     

Proteasomes in corneal epithelial cells and cultured autologous oral mucosal epithelial cell sheet (CAOMECS) graft used for the ocular surface regeneration

Purpose

This study focuses on characterizing proteasomes in corneal epithelial cells (CEC) and in cultured autologous oral mucosal epithelial cell sheets (CAOMECS) used to regenerate the ocular surface.

GC-MS method for the simultaneous determination of β-blockers, flavonoids, isoflavones and their metabolites in human urine

A sensitive and selective method based on gas chromatography hyphenated to mass spectrometry (GC-MS) for the screening of 23 different compounds including β-blockers, flavonoids, isoflavones and metabolites in human urine sample was developed and validated. The present paper reports, for the first time, the method for the simultaneous determination of β-blockers, isoflavones, flavonoids and metabolites in human urine samples. When flavonoids are ingested in combination with drugs that have a narrow therapeutic range, interactions between flavonoids and drugs should be investigated.Substances of interest were extracted from urine samples by solid-phase extraction (SPE) employing a mixture of tert-butyl methyl ether:methanol:formic acid (4.5:4.5:1; v/v/v) as a mobile phase and Oasis HLB (Waters) as a stationary phase. Before extraction, urine samples were incubated with β-glucuronidase/sulfatase in order to achieve enzymatic hydrolysis. Before GC-MS analysis the analytes had to be derivatized with N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) into their trimethylsilyl derivatives by incubating for 60 min at 60 °C. Statistical central composite design and response surface analysis were used to optimize the derivatization reagent. These multivariate procedures were efficient in determining the optimal separation condition, using peak areas as responses.The calibration curves were indicative of high linearity (r² ≥ 0.9992) in the range of interest for each analyte. LODs (S/N = 3) ranged between 0.6 and 9.7 ng/ml. Intra-day and inter-day precision (CV, %) was less than 4.96%, accuracy between 0.01 and 4.98% and recovery was found in the range from 70.20 to 99.55%.The developed method can be applied to the routine determination of examined compounds’ concentrations in human urine. Moreover the method is suitable for detecting pharmaceutical compounds containing β-blockers, isoflavones and flavonoids in urine after administration to humans.     

Stratified treatment of localized cervical esophageal squamous cell carcinoma induced by neoadjuvant immunotherapy plus chemotherapy (SCENIC)

BackgroundDefinitive chemoradiation is the preferred treatment for cervical esophageal carcinoma (CEC), per the National Comprehensive Cancer Network (NCCN) guidelines. However, in treatment failures, salvage surgery poses significant technical challenges. If non-responders could be identified, prior to chemoradiation, these patients may benefit from primary esophagectomy. Programmed cell death protein 1 (PD-1) inhibitor is widely used and recognized as an effective treatment method in various cancers including esophageal cancer. Therefore, we propose to screen for treatment response to neoadjuvant immunotherapy plus chemotherapy to select patients who are radiosensitive and potential candidates for laryngeal preservation. While non-responders are likely to be insensitive to chemoradiation would be offered radical esophagectomy.MethodsA total of 36 patients with histopathologically-confirmed locally advanced CEC have been enrolled in our study. All participants will receive 2 cycles of induction therapy, which was tislelizumab combined with paclitaxel and carboplatin. Patients will be classified into 3 groups according to their response to induction therapy: a remarkable response (RR) group, limited partial response (LPR) group, and poor response (POR) group. Stratified patients will receive the following follow-up treatments: those in the RR group will receive dCRT, and those in the LPR and POR groups will undergo radical surgery. Then, participants in the RR group will be administrated with tislelizumab alone for 1 year. The choice of postoperative treatment for patients in the LPR and POR groups will depend on the patient’s condition, including chemotherapy, radiotherapy, immunotherapy, or follow-up. The primary endpoint of the study is the 2-year event-free survival (EFS). The secondary endpoints are disease-free survival (DFS), regression-free survival (RFS), objective response rate (ORR), and 5-year overall survival (OS). At the same time, we will assess the patient’s quality of life (QoL).ConclusionsScreening CEC patients after immune-induction therapy combined with chemotherapy using different treatment strategies might lead to improvements in their QoL and OS time. No relevant double-endpoint studies have been reported until now. Our study is the first multicenter, prospective, exploratory study to seek the optimal treatment for locally advanced CEC patients. The results may offer high-level evidence for future CEC treatment.Trial RegistrationChictr.Org identifier: ChiCTR2200057732.     

Aortic valve sparing in 120 patients with aortic root aneurysms

Introduction and objectives

Several aortic valve sparing techniques have been described for the treatment of aortic root aneurysms. We report our experience using the reimplantation technique in 120 patients.

Methods

Between March 2004 and October 2010, 120 patients with aortic root aneurysms underwent David operations. Of these, 51 were diagnosed with Marfan syndrome. Mean patient age was 31 ± 12 years. The mean diameter of the sinuses of Valsalva was 51 ± 5 mm and moderate/severe aortic regurgitation was present in 16% of these patients. In the other 69 patients mean age was 56 ± 14 years, the mean diameter of the sinuses of Valsalva was 53 ± 7 mm and moderate/severe aortic regurgitation was present in 66%. A bicuspid aortic valve was presented in 14 cases.

Results

Hospital mortality was 1.7%. Mean follow-up was 37 ± 21 months; 94% of the patients survived and 96% had an aortic regurgitation below grade II during 5 years of follow-up. One patient required re-operation because of severe aortic regurgitation. No endocarditis or thromboembolic complications have been documented, and 96% of the patients did not receive any anticoagulation therapy.

Conclusions

Short- and mid-term results with the reimplantation technique for aortic root aneurysms are excellent. This technique prevents the need for chronic anticoagulation treatment as well as the complications arising from mechanical prostheses, and it should be the treatment of choice for young patients.Full English text available from: www.revespcardiol.org     

Cell-cell contacts prevent anoikis in primary human colonic epithelial cells

BACKGROUND & AIMS: Colonic epithelial cells (CECs) receive important survival signals from the extracellular matrix and undergo detachment-induced apoptosis (anoikis) as soon as they lose their cell-matrix anchorage. In contrast to the established role of cell-matrix contact, the role of cell-cell contacts as a physiologic survival factor for CECs is less clear. METHODS: Intact CEC crypts gently centrifuged to form a cell aggregate in which cell-cell contacts were maintained. Induction of apoptosis was assessed by Western Blot analysis, colorimetric assays, DNA electrophoresis, 4',6-diamidino-2-phenylindole staining, and flow cytometry. Activation of survival pathways was analyzed by Western blot. The role of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (Erk)1/2, epidermal growth factor receptor, phosphatidylinositol 3-kinase (PI3-K), and Src signaling was investigated using specific inhibitors. RESULTS: Despite a complete loss of cell-matrix adhesion after CEC isolation, activation of caspases was blocked and anoikis was prevented when cell-cell contacts were preserved. CECs with preserved cell-cell contacts exhibited a rapid dephosphorylation of focal adhesion kinase. Aggregated CECs had stable levels of active beta-catenin and phosphorylated Akt, Erk1/2, and epidermal growth factor receptor, but CECs undergoing anoikis rapidly degraded beta-catenin and dephosphorylated Akt. Inhibition of Src- and PI3-K-dependent signaling reversed the antiapoptotic effect of cell-cell contact preservation, while inhibition of the MEK pathway had no effect. CONCLUSIONS: Integrity of cell-cell contacts compensates for the loss of cell-matrix contact-mediated survival signals in CECs and prevents apoptosis. Cell-cell contact-triggered CEC survival involves antiapoptotic signaling through beta-catenin-, Src-, and PI3-K/Akt- but not through MEK- and focal adhesion kinase-dependent pathways.     

Improving the CellSearch® system

Introduction: The CellSearch® CTC test enumerates tumor cells present in 7.5 ml blood of cancer patients. improvements, extensions and different utilities of the cellsearch system are discussed in this paper.

Areas covered: This paper describes work performed with the CellSearch system, which go beyond the normal scope of the test. All results from searches with the search term ‘CellSearch’ from Web of Science and PubMed were categorized and discussed.

Expert commentary: The CellSearch Circulating Tumor Cell test captures and identifies tumor cells in blood that are associated with poor clinical outcome. How to best use CTC in clinical practice is being explored in many clinical trials. The ability to extract information from the CTC to guide therapy will expand the potential clinical utility of CTC.     

WIRION Embolic Protection System in Lower Extremity Arterial Interventions: Results of the Pivotal WISE LE Trial

Objectives

The WISE LE (WIRION? EPS in Lower Extremities Arteries) study was designed to assess the clinical performance of the WIRION Embolic Protection System (EPS) in subjects undergoing lower extremity atherectomy for the treatment of peripheral artery disease.