Post-neoadjuvant strategies in breast cancer: From risk assessment to treatment escalation

The post-neoadjuvant setting in early breast cancer represents an attractive scenario for adjuvant clinical trials, offering the opportunity to test new drugs or combinations in high-risk patients who did not achieve pathologic complete response after primary treatment. No standard therapies are routinely proposed to patients with residual disease after neoadjuvant chemotherapy and few trials have explored this setting. To date, only one randomized phase III study showed the benefit of additional capecitabine after neoadjuvant chemotherapy, and international guidelines recommend at least to consider its use, particularly for triple negative breast cancer. Therefore, the management of these patients is still a clinical challenge, with limited data supporting the use of an additional adjuvant non-cross-resistant chemotherapy. Escalation strategies are currently under evaluation, with new agents proposed as supplementary post-neoadjuvant treatment (e.g. platinum salts, capecitabine, poly ADP-ribose polymerase inhibitors, immune checkpoint inhibitors, cyclin-dependent kinase 4/6 inhibitors). Based on these premises, selection criteria are critical to identify patients who may benefit from post-neoadjuvant therapies, through the validation of prognostic and predictive biomarkers for a reliable risk assessment and estimation of benefit.The present review summarizes the efforts in introducing new therapeutic options for patients with breast cancer and residual disease after neoadjuvant treatment, with a particular focus on the ongoing clinical trials and useful biomarkers for risk stratification.     

Factors influencing development of residual stresses during crystallization firing in a novel lithium silicate glass-ceramic

ObjectiveDevelopment of residual stresses is a potential source of premature fractures in glassy materials, being of special interest in novel lithium silicate glass-ceramics that require a crystallization firing to achieve their final mechanical properties. The aim of this work was to assess the influence of various firing tray systems and the application of different cooling protocols on the development of residual stresses in Suprinity PC crowns. Their effect on the in vitro lifetime of the restorations was also studied.MethodsThirty crowns were milled out of Suprinity PC blocks and crystallized using one of five different commercial firing tray systems (n = 6). Samples in each group were cooled following a fast (FC = 5.5 °C/s), a slow (SC = 0.4 °C/s) or the manufacturer’s reference cooling (REF ). Obtained crowns were sagittally or transversally sectioned and the magnitude and distribution of residual stresses was determined using the light birefringence method. Extra crowns of three of the subgroups (n = 8) were produced and submitted to chewing simulation for 10⁶ cycles or until fracture ensued.ResultsAverage residual stresses ranged between 0 and 1.5 MPa (peaks of 5 MPa). Highest stress magnitudes were observed at the support areas of groups using firing pins, leading to thermal cracks in FC samples and premature failures in the REF subgroup. The use of fibrous pads and firing pastes limited the development of residual stresses, whereas application of SC regimes extended the lifetime of the restorations.SignificanceDevelopment of residual stresses during crystallization firing in lithium silicate glass-ceramics results critical for their mechanical performance and should be therefore avoided by ensuring a homogenous cooling of the structures.     

吉非罗齐中有机溶剂残留量的顶空毛细管GC测定

建立了顶空毛细管GC法测定吉非罗齐中甲酸乙酯、THF和甲基环己烷3种有机溶剂的残留量。采用HP-1毛细管柱，溶剂DMA，内标乙酸乙酯。平均同收率分别为99．8％、100．3％、100．0％，RSD分别为0．71％、1．51％和1．76％。     

枳椇子总黄酮提取工艺及其解酒作用

分别用水和乙醇作为溶剂加热提取枳椇子中的总黄酮,用比色法测定黄酮的含量,分别以提取时间、加热温度、料液比、提取次数等因素进行正交试验.对两种提取方法进行比较,确定各因素对提取效果的影响并对其解酒作用进行研究.水提取法的最优条件是：100 ℃,料液比1 g：8 mL,加热0.5 h,回流提取3次;醇提取法的最佳条件：80 ℃,料液比1 g：6 mL,加热1.5 h,以体积分数50%的乙醇回流提取3次.实验结果显示,醇提取法比水提取法效果更好,枳椇子提取液具有一定的解酒作用.     

牙冠延长术在残根残冠修复中的临床疗效

目的评价牙冠延长术在牙体缺损达龈下的残根残冠修复中的临床疗效。方法自2004年5月至2005年6月,对32例患者的36颗牙体缺损达龈下的患牙,术前按断端位于龈下最深距离分为A组(20颗患牙,距离<3.0mm)和B组(16颗患牙,3.0mm≤距离≤4.0mm),均采用牙冠延长术暴露龈下牙体断面,术后6周行桩冠修复。分别记录和比较手术前、后牙周探诊深度(PD)、菌斑指数(PLI)、龈沟出血指数(SBI)和牙齿松动度,以观察临床疗效。结果术后随访患者6个月,两组病例术后6周牙体断端均暴露较好、龈缘颜色正常,术后修复效果有效率为100%,满意率为77.78%。A组术后无松动,修复效果满意;B组术后50.00%出现Ⅰ度松动,修复效果欠佳,两组修复效果比较差异有显著意义(P<0.05)。术后各阶段两组的PD、PLI、SBI均明显优于术前(P<0.05),但两组术后牙周指数比较差异无显著意义(P>0.05)。结论牙冠延长术有利于残根残冠的保存和修复,但要注意适应证的选择。     

GC法测定金银三七胶囊中的冰片的含量

目的：建立金银三七胶囊中冰片的含量测定方法。方法：采用GC法，色谱柱为10％PEG-20M；FID氢火焰检测器：柱温为115℃。结果：冰片在0．02559-0．5118μg范围内线性良好。加样回收率为99．9％，RSD％为1．94％（n=9）。结论：方法简便，可行，重现性良好，结果准确，可加强金银三七胶囊的质量控制。     

头孢西丁钠中甲醇残留量的顶空毛细管GC法测定

建立了顶空毛细管GC法测定头孢西丁钠中甲醇残留量，并探讨了药物结构中甲氧基对测定的影响。采用DM-624石英毛细管柱，检测器为FID。甲醇在0．02～5mg／ml浓度范围内，与峰面积线性关系良好（r=0．9999）。方法平均回收率为97．7％，RSD为1．8％。     

Fluorimetric assay of rufloxacin in serum and in pharmaceutical formulations

A simple and rapid fluorimetric method for the determination of 9-fluoro-10-[N-(4′-methyl)piperazinyl]-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-d,e][1–4]benzothyazin-6-carboxylic acid hydrochloride (MF 934), in serum and in pharmaceutical formulations, has been developed based on its strong fluorescence, in 0.1 N H₂SO₄, at 526 nm (excitation wavelength at 340 nm). The procedure which involves the direct dilution of the sample requires only a few minutes and the sample volume is only 20–100 μl of serum, depending on the drug concentration. Tedious sample preparation procedures such as extraction, deproteinization, or centrifugation are not necessary. The minimum concentration that can be detected is 0.3 ng ml⁻¹, the standard curve in 0.1 N H₂SO₄ was found to be linear from 0.005 to 1.5 μg ml⁻¹ and from 0.01 to 0.07 g in plasma after dilution with 0.1 N H₂SO₄.     

灵芝菌合剂中灵芝多糖含量的测定

目的：探讨灵芝菌合剂中灵芝多糖含量的检测方法。方法：采用分光光度法，以无水葡萄糖为对照品，检测波长为490nm。结果：此方法在0～120μg范围内线性关系良好，灵芝多糖的平均回收率为99．09%。RSB为1．14％。结论：本法简便快捷，准确度高，重现性好，可作为本制剂的质控方法。