Phase II study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA

Objective:Apatinib is an oral TKI targeting VEGFR-2. Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated mBC. Oral vinorelbine also holds promise as a treatment of choice in patients with mBC. This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated mBC. In addition, we detected gene variants in ctDNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative mBC who were pretreated with anthracycline/taxanes. Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m² on days 1, 8, and 15 of every cycle (3 weeks). The primary endpoint was PFS. The secondary endpoints were ORR, CBR, OS, and safety. Patients eligible for ctDNA detection were evaluated before and during treatment.Results:Forty patients were enrolled. The median PFS was 5.2 months (95% CI, 3.4–7.0 months), and the median OS was 17.4 months (95% CI, 8.0–27.0 months). The ORR was 17.1% (6/35), and the CBR was 45.7% (16/35). The most common AEs included gastrointestinal reaction, myelosuppression, and hypertension. In 20 patients, ctDNA was detected at baseline and during treatment. A significant difference was found in PFS for undetected vs. detected baseline ctDNA (13.9 months vs. 3.6 months, P = 0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative mBC, with acceptable and manageable toxicity profiles. Patients with no gene variant detected and lower variant allele frequencies in ctDNA at baseline showed longer PFS.     

Bioadhesive film formed from a novel organic-inorganic hybrid gel for transdermal drug delivery system

A novel organic-inorganic hybrid film-forming agent for TDDS was developed by a modified poly(vinyl alcohol) (PVA) gel using γ-(glycidyloxypropyl)trimethoxysilane (GPTMS) as an inorganic-modifying agent, poly(N-vinyl pyrrolidone) (PVP) as a tackifier and glycerol (GLY) as a plasticizer. The prepared gels can be applied to the skin by a coating method and in situ form very thin and transparent films with good performance, comfortable feel and cosmetic attractiveness. The key properties of the bioadhesive films produced from the hybrid gels were investigated and the results showed that the incorporation of appropriate GPTMS (GPTMS/(PVA + GPTMS) in the range of 20-30%) into the PVA matrix not only can significantly enhance mechanical strength and skin adhesion properties of the resultant film, but also can decrease the crystalline regions of PVA and hence facilitate the diffusion of water vapor and drug. Furthermore, the investigations into in vivo skin irritation suggested the films caused non-irritation to skin after topical application for 120 h. In conclusion, the bioadhesive films formed from organic-inorganic hybrid gels possessed very good qualities for application on the skin and may provide a promising formulation for TDDS, especially when the patient acceptability from an aesthetic perspective of the dosage form is a prime consideration.     

手术患者交接过程中护理过失的原因及对策

对手术室与病房交接过程中发生的46例护理过失的原因进行分析,提出应强化安全意识教育,制定护士交接制度、患者转运制度,规范交接记录单等,增强科室间协调合作关系,保障患者安全。     

急性肺损伤鼠类模型的研究进展

急性呼吸窘迫综合征是导致急性呼吸衰竭的重要原因,已经成为重症监护病房患者发生率和死亡率最高的疾病之一,其根本原因是目前急性呼吸窘迫综合征的发病机制复杂多样且尚未明确。因此,建立合适的急性肺损伤鼠类模型有助于研究急性呼吸窘迫综合征的发病机制、治疗方案及预防策略。本文就实验动物选择、急性肺损伤模型建立方法及其应用进展进行综述。     

手术室质量追溯体系在器械处管理的应用

目的提高手术器械的清洗质量,优化准备路径,合理排班,提高工作效率。方法采用质量追溯体系,对器械清洗、打包和准备路径中的问题进行分析和优化,试行6个月后评价效果。结果路径优化后器械清洗质量明显提高;器械清洗、打包路径中的缺陷和总工作时间降低;护士和清洗人员间因交接不清的矛盾减少,护士和医生对器械准备的满意度提高。结论手术室质量追溯体系用于器械的清洗、打包和准备路径优化的管理,可降低工作中的缺陷,减少人力资源的浪费,提高工作效率。     

pH‐Responsive Nanoparticles for Controllable Curcumin Delivery: The Design of Polycation Core with Different Structures

To achieve low leakage at pH 7.4, pH‐controlled drug release remains a major challenge of cancer nanomedicine. Here, pH‐responsive mPEG₁₁₃‐b‐polycaprolactone (PCL)_x‐b‐PAEMA_y (PELAx) nanoparticles (NPs)‐pH7.4 with different poly(2‐azepane ethyl methacrylate) (PAEMA) lengths and PELA4 nanoparticles (NPs)‐pHx with different pH conditions of preparing NPs based on mPEG₁₁₃‐b‐PCL_x‐b‐PAEMA_y are prepared to investigate influences of PAEMA lengths and pH condition of preparing NPs on properties of NPs. PELAx NPs‐pH7.4 and PELA4 NPs‐pHx both undergo differently sharp property changes of size, charge, pH‐responsive drug release, cellular uptake, and cytotoxicity, because of the protonation of PAEMA block (pKa ≈ 6.5–6.7). Among PELAx NPs‐pH7.4 and PELA4 NPs‐pHx, it can be found that the NPs prepared at pK_a value of PAEMA exhibited exciting pH‐responsive drug release, improving cellular uptake ability and obvious high cytotoxicity toward HepG‐2 cells. This system not only holds great potential for drug delivery but also provides a new strategy to prepare pH‐responsive NPs.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Compact solar autoclave based on steam generation using broadband light-harvesting nanoparticles

The lack of readily available sterilization processes for medicine and dentistry practices in the developing world is a major risk factor for the propagation of disease. Modern medical facilities in the developed world often use autoclave systems to sterilize medical instruments and equipment and process waste that could contain harmful contagions. Here, we show the use of broadband light-absorbing nanoparticles as solar photothermal heaters, which generate high-temperature steam for a standalone, efficient solar autoclave useful for sanitation of instruments or materials in resource-limited, remote locations. Sterilization was verified using a standard Geobacillus stearothermophilus-based biological indicator.     

开腹与微创切除子宫肌瘤两种术式的临床评估

目的 探讨开腹与微创下行子宫肌瘤切除两种术式在临床应用中的优、缺点。方法回顾性分析106例子宫肌瘤切除病例，将其分为开腹与微创2组，对其术中、术后各种情况进行比较分析。结果 两种术式在手术时间、术中出血量、术后肌瘤复发率、术后2年妊娠率方面差异无显著性，而术后排气时间，术后4h、24h自主疼痛评分，住院时间及1年妊娠率差异有显著性（P〈0．05）。结论 两种术式各有优、缺点，在严格掌握微创适应证前提下宜行微创术。     

Preference of distance learning methods among post-graduate occupational physicians and hygienists

BACKGROUND: The Centre for Occupational and Environmental Health at the University of Manchester has successfully run distance-learning courses for a number of decades. These are based on hundreds of pages of (paper-based) written text, specially commissioned, packaged and distributed in eight binders. Converting printed text to an online format has the potential to improve learning through the benefits of information and communication technology as well as to save printing and distribution costs. AIM: To determine which distance learning method is preferred by postgraduate occupational health students: paper-based text, or online text with embedded interactive questions and separate practical exercises. METHODS: From approximately 50 paper-based textual course sub-units, one was converted to an online format, incorporating a variety of interactive text and supplemental practical exercises. Occupational medicine and hygiene students were provided with both the paper-based and online versions and asked, via anonymous postal questionnaire, a series of questions, including their preference for future course sub-units. RESULTS: Sixty-two replies were received from 91 registered students (68% response). Apart from one student who had never tried the internet, all others described themselves as 'frequent' or 'occasional' internet users, with 78% having access both at home and work. Opinion was overwhelmingly positive with regard to ease of navigation, quality of the interactive exercises and online photo quality. Students tended to prefer multiple-choice questions and photo exercises and disliked interactive functions asking for words to complete paragraphs. Regarding preference for future teaching sub-units, the majority of students answering this question (67%) expressed a desire for mostly paper-based text supplemented with interactive online exercises. CONCLUSION: Currently enrolled students prefer core teaching materials to remain in the printed medium, with the addition of online practical exercises to supplement learning.     

Risk of serious gastrointestinal bleeding in living kidney donors

Individuals with moderate‐to‐severe reduced renal function have greater risk of gastrointestinal bleeding than those with normal renal function. We conducted a retrospective matched cohort study to assess whether living kidney donors share a similar risk. We reviewed pre‐donation charts for living kidney donations from 1992 to 2009 in Ontario, Canada, and linked this information to healthcare databases. We selected healthy non‐donors from the general population and matched ten non‐donors to every donor. Of the 2009 donors and 20 090 matched non‐donors, none had evidence of gastrointestinal bleeding prior to cohort entry. The cohort was followed for a median of 8.4 yr (maximum 19.7 yr; loss to follow‐up <7%). There was no significant difference in the rate of hospitalization with gastrointestinal bleeding in donors compared to non‐donors (18.5 vs. 14.9 events per 10 000 person‐years; rate ratio 1.24; 95% confidence interval [CI] 0.85–1.81). Similar results were obtained when we assessed the time to first hospitalization with gastrointestinal bleeding (hazard ratio 1.25, 95% CI 0.87–1.79). In conclusion, we found living kidney donation was not associated with a higher risk of hospitalization with gastrointestinal bleeding. These results are reassuring for the safety of the practice.