Corrosion Resistance of 3D Printed Ti6Al4V Gyroid Lattices with Varying Porosity

Corrosion of medical implants is a possible failure mode via induced local inflammatory effects, systemic deposition and corrosion related mechanical failure. Cyclic potentiodynamic polarisation (CPP) testing was utilized to evaluate the effect of increased porosity (60% and 80%) and decreased wall thickness in gyroid lattice structures on the electrochemical behaviour of LPBF Ti6Al4V structures. The use of CPP allowed for the landmarks of breakdown potential, resting potential and vertex potential to be analysed, as well as facilitating the construction of Tafel plots and qualitative Goldberg analysis. The results indicated that 60% gyroid samples were most susceptible to the onset of pitting corrosion when compared to 80% gyroid and solid samples. This was shown through decreased breakdown and vertex potentials and were found to correlate to increased lattice surface area to void volume ratio. Tafel plots indicated that despite the earlier onset of pitting corrosion, both gyroid test groups displayed lower rates of corrosion per year, indicating a lower severity of corrosion. This study highlighted inherent tradeoffs between lattice optimisation and corrosion behaviour with a potential parabolic link between void volume, surface area and corrosion being identified. This potential link is supported by 60% gyroid samples having the lowest breakdown potentials, but investigation into other porosity ranges is suggested to support the hypothesis. All 3D printed materials studied here showed breakdown potentials higher than ASTM F2129′s suggestion of 800 mV for evaluation within the physiological environment, indicating that under static conditions pitting and crevice corrosion should not initiate within the body.     

英利昔单抗在消化系统疾病中的应用状况及前景

目的:评价英利昔单抗在消化系统相关疾病治疗中的疗效和安全性。方法:收集国外相关文献进行综述、分析。结果及结论:英利昔单抗作为新一代的抗炎药通过中和TNF-α的生物学效应而发挥抗炎作用。对于克罗恩病、溃疡性结肠炎、酒精性肝病等消化系统疾病都有较好疗效,且在推荐的治疗范围内安全性良好。     

Costs and effects of secondary prevention with perindopril in stable coronary heart disease in Poland: an analysis of the EUROPA study including 1251 Polish patients

OBJECTIVES: To estimate the long-term impact of treatment with perindopril on costs and health effects in patients with stable coronary artery disease in Poland. METHODS: The cost-effectiveness analysis was based on data from a randomized double-blind, placebo-controlled trial. A decision-tree analysis was employed, including Monte Carlo and bootstrapping techniques. This study was a sub-study of the EUROPA (European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease) trial (n = 12 218; mean follow-up 4.2 years). Resource use was based on data from Polish EUROPA study patients (n = 1251), while effectiveness was based on the whole EUROPA study. The health gain of perindopril in life-years was based on overall EUROPA study results, and the adapted Polish life expectancy of patients not dying during the trial. Costs were calculated in new Polish zloty (PLN), year 2003 values; euro1 = PLN4.053. Only direct healthcare costs related to cardiovascular events and medication use were studied. RESULTS: When observed mortality was combined with life expectancy beyond the end of the study, perindopril use showed a gain in life expectancy of 0.182 life-years (SD +/- 0.129) at a cost of PLN1983 (SD +/- 103) with discounting of 5% per annum on costs and no discounting on effects. This resulted in an incremental cost-effectiveness ratio (ICER) of PLN10 896 per life-year gained. The probability that the ICER for perindopril was below the threshold of PLN60 000 was 88%. The overall results were insensitive to discount rates for costs and life-years. CONCLUSIONS: Perindopril leads to a reduction in the risk of coronary events among patients with stable heart disease. When the expected improvement in life expectancy is combined with associated medical costs, there is a high probability that perindopril is cost effective, given the threshold of PLN60 000 per life-year gained.     

醋酸铅对豚鼠耳蜗橄榄束传出神经毒性的研究

目的探讨醋酸铅对豚鼠内侧橄榄耳蜗传出神经的损害。方法 70只成年健康豚鼠随机分为对照组和实验组。对照组(10只)豚鼠腹腔注射生理盐水1ml,共7次。实验组又分为高铅组和低铅组(各30只),分别每天1次腹腔注射0.25%醋酸铅溶液40mg/kg和10mg/kg,连续一周,分别于停药后14、28天(各15只))进行血铅含量和畸变产物耳声发射(DPOAE)检测,检测完成后断头处死,行基底膜铺片染色。结果实验组醋酸铅染毒后,血清中铅含量迅速升高。对照组和低铅组耳蜗传出神经分布均匀,神经纤维连续,DPOAE出现了不同程度的对侧声抑制效应,低铅组14天和28天抑制幅度分别为3.06±1.19dB和2.86±1.33dB;高铅组14天后耳蜗传出神经纤维连续性中断,乙酰胆碱酯酶终末反应物减少,DPOAE对侧声抑制幅度下降为0.74±0.61dB;高铅组28天后传出神经损害最为显著,DPOAE未引出。结论铅可对豚鼠内侧橄榄耳蜗传出神经产生不可逆性的损害。     

Phase IIb study of pembrolizumab combined with S‐1 + oxaliplatin or S‐1 + cisplatin as first‐line chemotherapy for gastric cancer

The KEYNOTE‐659 study evaluated the efficacy and safety of first‐line pembrolizumab plus S‐1 and oxaliplatin (SOX) (cohort 1) or S‐1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open‐label phase IIb study enrolled patients with advanced programmed death‐ligand 1 (PD‐L1)‐positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)‐negative G/GEJ adenocarcinoma. The primary end‐point was the objective response rate (ORR). Other end‐points were duration of response (DOR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow‐up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment‐related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD‐L1‐positive, HER2‐negative G/GEJ adenocarcinoma.     

Evaluation of the anti-proliferative properties of selected psoriasis-treating Chinese medicines on cultured HaCaT cells

Psoriasis is a chronic inflammatory skin disorder, which affects approximately 2-3% of the population worldwide. The current conventional therapy cannot offer satisfactory clinical results for most of the patients, largely due to the fact that many anti-psoriatic drugs have serious side effects and psoriasis is prone to developing drug resistance after long term exposure. Traditionally, Chinese herbal medicine has been extensively used to treat psoriasis and produced promising clinical results; however, its underlying mechanisms of action have not been systematically investigated. The aim of this study was to investigate those Chinese medicinal materials, which are commonly prescribed in Chinese medicine practice for psoriasis, for their anti-proliferative effects on HaCaT cells in vitro. Sixty Chinese medicinal materials were selected and extracted with 80% aqueous ethanol. The dry extracts were evaluated for their anti-proliferative activities by microplate SRB and MTT assays. Three Chinese medicinal materials i.e. the root of Rubia cordifolia L. (Rubiaceae), Realgar and the rhizome of Coptis chinensis Franch. (Ranunculaceae) were found to have significant anti-proliferative effects, with IC(50) being 1.4, 6.6 and 23.4 microg/ml, respectively as measured by MTT assay. While Realgar was also able to modestly inhibit the growth of Hs-68 cells in vitro, Rubia cordifolia and Coptis chinensis did not exert cytotoxicity to this human fibroblast cell line.     

Effectiveness of doxifluridine (5′-DFUR)/docetaxel against advanced/recurrent gastric cancer showing resistance to various anticancer drug regimens

A 58-year-old man was diagnosed as having type 3 gastric cancer (poorly differentiated adenocarcinoma). He underwent total gastrectomy with splenectomy, as well as D3 dissection, and received postoperative chemotherapy combining oral uracil and futrafur (UFT) with cisplatin (CDDP), but results showed recurrence of multiple abdominal lymph node metastases around the aorta. He therefore received various anticancer drug regimens (irinotecan [CPT-11]/CDDP; 1 M tegafur-0.4 M gimeracil-1 M oteracil potassium [TS-1], methotrexate (MTX)/5-fluorouracil); however, final results showed growth of lymph node metastasis and simultaneous worsening of his general condition. The patient then received combined administration of doxifluridine (5′-DFUR)/docetaxel (5′-DFUR, 1000 mg/body [666.7 mg/m ² ], given by consecutive daily administration, orally, for days 1–14; and docetaxel, 80 mg/body [60 mg/m ² ], on day 8, by venous drip, every 3 weeks). Three courses of this regimen resulted in approximately 90% reduction of the abdominal lymph node size, disappearance of the right cervical lymph node metastasis, reductions of the levels of two tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA]19-9), and improvement of his general condition. In total, seven courses of the regimen were carried out. The patient died on day 298 after starting this combined regimen and showed a response period of 126 days. The primary toxicity identified was neutropenia (grade 4), as well as other low-grade (grade 1, 2) hematological and nonhematological toxicities. In the field of gastric cancer treatment, especially for patients showing multiple resistance to anticancer drugs, an effective therapy is critically needed. Received: January 15, 2002 / Accepted: July 8, 2002 Offprint requests to: A. Sato     

Fetal intraventricular bleeding possibly due to maternal vitamin K deficiency

We report a rare case of fetal intraventricular bleeding possibly due to maternal vitamin K deficiency. A 20-year-old woman was admitted to our hospital due to impending premature delivery and loss of dietary intake at 28 weeks of gestation. Her blood examination showed metabolic alkalosis, prolonged prothrombin time, and extremely high level of plasma des-gamma-carboxyprothrombin (protein induced by vitamin K absence, PIVKA-II). Intraventricular hemorrhage was demonstrated by ultrasonography 6 days after admission. She delivered a 2,288-gram girl infant at 40 weeks of gestation. Cranial computerized tomography and magnetic resonance images obtained postnatally demonstrated a reduced cerebral parenchyma adjacent to the interior side of the right lateral ventricle and the deficit of left cerebellum. The infant's head control was insufficient and central impaired hearing was noted at 6 months of life.     

Anonymity and openness and the recruitment of gamete donors. Part I: semen donors

Since 1 April 2005, gamete donors in the United Kingdom (UK) have to be willing, in the future, to be identified to offspring should the offspring want this. This change in law has lead to considerable anxiety about the future availability of donors. This paper presents an overview of the research evidence concerning semen donors' views on anonymity and openness, as it appears in referred journals since 1995. Research evidence that is available, but not yet been published in referred journals, is also reviewed. The nature of this evidence is analysed and criticized. Research on the views of potential semen donors is also reviewed, as is the evidence that is available from jurisdictions that have changed the law and required donor openness. The evidence shows that it is possible to recruit semen donors who are required to be identifiable in the future. The evidence, while not conclusive, points to an open system attracting different kinds of men than an anonymous system, and this has clear implications for future recruitment policies. The evidence-based approach to recruitment of gamete donors challenges some of the beliefs, attitudes and fears that have been associated with this law change in the UK, and in other countries where similar changes have taken place.