A Proposal for an Alternative Approach to Particle Size Method Development During Early-Stage Small Molecule Pharmaceutical Development

Particle size analysis in the pharmaceutical industry has long been a source of debate regarding how best to define measurement accuracy; the degree to which the result of a measurement or calculation conforms to the true value. Defining a “true” value for the size of a particle can be challenging as the output of its measurement will differ because of variations in measurement approaches, instrumental differences and calculation methods. Consequently, for “real” particles, a universal “true” value does not exist and accuracy is therefore not a definable characteristic. Accordingly, precision is then a measure of the ability to reproducibly achieve a measurement of unknown relevance.This article proposes, in place of accuracy, a means to define the “appropriateness” of a measurement in line with the critical quality attributes (CQA) of the material being characterized. The decision as to whether the measurement is correct should involve a link to the CQA; that is, correlation should be demonstrated, without which the measured particle size cannot be defined as a critical material attribute.Correspondingly, methods should also be able to provide sufficient precision to demonstrate discrimination relating to variation in the CQA. The benefits and challenges of this approach are discussed.     

中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

<i>Sinomenium</i> Inhibits the Viability of Hepatoma Carcinoma Cells through Activating IFNA2

Hepatocellular carcinoma (HCC) ranks the sixth place of most common cancers. Meanwhile, it is the tertiary mortality cause of cancer. There is no effective therapeutic method to prevent and treat the liver cancer. Sinomenine is a kind of Chinese traditional medicine herbal, it is reported that it can inhibit the viability of several cancer cells. The study is to explore whether sinomenine is also able to inhibit the cell viability of HCC and its potential mechanism. The IC50 of sinomenine in BEL-7402 cells was 5.351 mmol/L, and the IC50 of sinomenine in SMMC-7721 cells was 6.204 mmol/L. The gene expression results showed the relative expression of FGF2, CCND2, DCN, F3, MMP7, NRG1, HMGB1, TRIM29, HAS2, EHF, CTGF, PLK2 were down-regulated, and the relative expression of VEGF A, CITED2, NUPR1, DDX58, IRF9, NAMPT, MMP1, NDRG1, HMGA2, PPARGC1A, IFIT2, PARP9, HEY1, LOX, ETV1, ISG15, BACH, CYLD were up-regulated. Moreover, the IPA analysis results suggested that IFIT3, IFIT1, OAS1, MX1, IRF9, IFI6, IFITM1, ISG15 were up-regulated in BEL-7402 cells treated with sinomenine by activating IFNA2. The findings presented in this study may provide a promising method for the prevention and treatment of liver cancer.     

The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury

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Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non–small cell lung cancer: A propensity-matched analysis

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

探讨基于近红外脑成像技术的阈下抑郁情志刺激反应机制研究可行性

近红外脑功能成像技术是近几年发展起来用于动态检测脑功能的方法,能够很好地反映抑郁人群认知活动期间大脑有氧代谢的变化,为阈下抑郁研究提供了一个新思路。本研究通过文献综述,结合中医情志理论,在过往研究的基础上基于近红外脑功能成像技术探讨中医情志刺激对阈下抑郁的反应机制,为后期研究提供理论与实践可行性的依据。     

Marr and Reductionism

David Marr's three-level method for completely understanding a cognitive system and the importance he attaches to the computational level are so familiar as to scarcely need repeating. Fewer seem to recognize that Marr defends his famous method by criticizing the “reductionistic approach.” This sets up a more interesting relationship between Marr and reductionism than is usually acknowledged. I argue that Marr was correct in his criticism of the reductionists of his time—they were only describing (cellular activity), not explaining (cognitive functions). But a careful metascientific account of reductionistic neuroscience over the past two decades reveals that Marr's criticisms no longer have force. Contemporary neuroscience now explains cognition directly, although in a fashion—causal-mechanistically—quite different than Marr recommended. So while Marr was correct to reject the reductionism of his day and offer an alternative method for genuinely explaining cognition, contemporary cognitive scientists now owe us a new defense of Marr's famous method and the advantages of its explanations over the type now pursued successfully in current reductionist neuroscience. There are familiar reasons for thinking that this debt will not be paid easily.     

Migration and Inducible Displacement of the Bicruciate-Stabilized Total Knee Arthroplasty: A Randomized Controlled Trial of Gap Balancing and Measured Resection Techniques

BackgroundThe goal of this study is to investigate the migration and inducible displacement of a bicruciate-stabilized (BCS) total knee arthroplasty implanted using gap balancing (GB) or measured resection (MR) surgical techniques. We hypothesized equal migration and displacement between the techniques.MethodsThe study is a single-blinded, prospective, randomized controlled trial, with allocation of 71 patients to either GB or MR groups. Fifteen patients were withdrawn, resulting in 31 patients in the GB group and 25 in the MR group. Patients received the JOURNEY II? BCS implant. Migration and inducible displacement were evaluated using radiostereometric analysis and patient examinations were performed at a 2-week baseline, and at 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperation.ResultsNo differences (P > .05) existed between GB and MR groups for any measurement of tibial or femoral migration. Both groups had tibial migrations below 0.5 mm from baseline to 6 months, and below 0.2 mm from both 6 months to 1 year and 1-2 years postoperation. No differences (P > .05) were found between GB and MR groups for inducible displacement.ConclusionNo differences were found in implant migration or inducible displacement between GB and MR groups. The BCS implant can be expected to have migration risks on par with industry standards and both surgical techniques are safe and effective options for implantation of this implant design.     

Relationship between EMG-detected and ultrasound-detected fasciculations in amyotrophic lateral sclerosis: A prospective cohort study

ObjectivesFasciculation potentials (FP) are an important consideration in the electrophysiological diagnosis of ALS. Muscle ultrasonography (MUS) has a higher sensitivity in detecting fasciculations than electromyography (EMG), while in some cases, it is unable to detect EMG-detected fasciculations. We aimed to investigate the differences of FP between the muscles with and without MUS-detected fasciculations (MUS-fas).MethodsThirty-one consecutive patients with sporadic ALS were prospectively recruited and in those, both needle EMG and MUS were performed. Analyses of the amplitude, duration, and number of phases of EMG-detected FPs were performed for seven muscles per patient, and results were compared between the muscles with and without MUS-fas in the total cohort.ResultsThe mean amplitude and phase number of FP were significantly lower in patients with EMG-detected FP alone (0.39 ± 0.25 mV and 3.21 ± 0.88, respectively) than in those with both FP and MUS-fas (1.22 ± 0.92 mV and 3.74 ± 1.39, respectively; p < 0.0001 and p = 0.017, Welch’s t-test).ConclusionSmall FP may be undetectable with MUS. MUS cannot replace EMG in the diagnostic approach for ALS.SignificanceClinicians should use a combination of EMG and MUS for the detection and quantitative analysis of fasciculation in ALS.