Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

Near-infrared spectroscopy in schizophrenia:A bibliometric perspective

BACKGROUND Compared with current methods used to assess schizophrenia,near-infrared spectroscopy(NIRS)has the advantages of providing noninvasive and real-time monitoring of functional activities of the brain and providing direct and objective assessment information.AIM To explore the research field of NIRS in schizophrenia from the perspective of bibliometrics.METHODS The Web of Science Core Collection was used as the search tool,and the last search date was April 21,2024.Bibliometric indicators,such as the numbers of publications and citations,were recorded.Bibliometrix and VOS viewer were used for visualization analysis.RESULTS A total of 355 articles from 105 journals were included in the analysis.The overall trend of the number of research publications increased.Schizophrenia Research was identified as an influential journal in the field.Kasai K was one of the most influential and productive authors in this area of research.The University of Tokyo and Japan had the highest scientific output for an institution and a country,respectively.The top ten keywords were“schizophrenia”,“activation”,“near-infrared spectroscopy”,“verbal fluency task”,“cortex”,“brain,performance”,“workingmemory”,“brain activation”,and“prefrontal cortex”.CONCLUSION Our study reveals the evolution of knowledge and emerging trends in the field of NIRS in schizophrenia.the research focus is shifting from underlying disease characteristics to more in-depth studies of brain function and physiological mechanisms.

P值和置信区间:联系与区别、误用与争论

P值和置信区间是统计推断中应用最为广泛的两个指标。然而,这两个指标(特别是P值)的误用和滥用问题已经引起了广泛的关注,美国统计协会甚至还发表了关于P值使用的警告声明。对于P值和置信区间的误用,其根源在于科研工作中,很多人对P值和置信区间的理解存在一定偏差甚至错误。至于P值和置信区间二者之间有何联系与区别,很多读者也许从未深入思考过这个问题。因此,本文期望以通俗易懂的方式介绍P值及置信区间的定义,分析二者之间的联系与区别,帮助读者正确理解P值与置信区间。此外,本文还列举了目前P值及置信区间存在的误用情况,以及国际上对于P值和置信区间之间的使用争论,以期帮助读者在今后的科研工作中正确地使用P值和置信区间。

剂量反应Meta分析中常见的统计学问题

剂量反应Meta分析(dose-response Meta-analysis,DRMA)是基于多项提供剂量反应关系数据的原始研究,对其剂量反应结果进行定量合并后得出综合剂量反应直线或曲线的一类Meta分析,广泛应用于循证证据产生及临床决策等方面。目前已发表DRMA结果的可靠性和文章质量水平不一,而且国际上暂无DRMA的统一报告规范。本研究系统梳理了DRMA的本质、各步骤统计方法及常见统计分析问题,以期从统计学角度提高国内学者对DRMA的整体理解,为提高DRMA的整体质量奠定一定理论基础。

I^(2)检验在Meta分析异质性评价中的误用

Meta分析异质性是指Meta分析纳入的各单项原始研究间存在的差异。选用恰当的方法或指标识别和测量异质性是评价Meta分析结果可靠性的重要步骤。尽管I^(2)检验是目前使用极为广泛的Meta分析异质性检验方法,但从I^(2)统计量定义可知,I^(2)检验并不能真实展现异质性大小,当前Meta分析异质性评价方法误用情况严重。本研究系统梳理Meta分析常用异质性评价方法,通过两个实例展示I^(2)统计量在Meta分析异质性检验中的误用情况,并介绍能够合理展现Meta分析异质性的统计指标,以期提高Meta分析异质性评价的可靠性和规范性。

Kai-Xin-San regulates synaptic plasticity through calcium signaling to alleviate symptoms of depression-like behavioral disorders in mice

Background:Kai-Xin-San,a classical Chinese medicine prescription,has been widely applied in the clinical therapy for depression,but its pharmacological mechanism remains to be further explored.Based on network pharmacology,molecular docking and animal experiments,the research is performed to exploit pharmacological mechanism of Kai-Xin-San for treating depression.Methods:Obtain chemical components and potential targets of Kai-Xin-San through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,Encyclopedia of Traditional Chinese Medicine and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine databases,and then screen the active ingredients of each herb in accordance with absorption,distribution,metabolism,and excretion.The GenCards,Online Mendelian Inheritance in Man,Therapeutic Target database and DrugBank databases were used to obtain the major targets of depression,and the STRING platform was used to construct the protein-protein interaction network and explore the potential protein functional modules in the network.The targets were subjected to Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis by STRING database and Metascape database.The interaction network of“Kai-Xin-San active components-depression-targets-pathways”was constructed by Cytoscape,and molecular docking verification was performed by Auto Dock tools.Finally,animal experiments were carried out for further verification.The chronic restraint stress depression model was established and mice were randomly divided into 4 groups:control group,chronic restraint stress group,fluoxetine group and Kai-Xin-San group.Behavioral tests were used to evaluate the depressive phenotype of mice.The expression of CaMKII-,synaptophysin,poststroke depression-95,and CACNA1C were all detected using a western blot.Results:Network analysis shows that Kai-Xin-San may mainly regulate calcium signaling pathway to exert antidepressant effects.A majority of the targets and components have good binding activity,according to the molecular docking studies.In the current study,behavioral tests showed that Kai-Xin-San could effectively alleviate depression-like behaviors in mice compared with the chronic restraint stress group,which effect was comparable to fluoxetine.Meanwhile,compared with the chronic restraint stress group,protein levels of CACNA1C,CaMKII-α,synaptophysin and poststroke depression-95 were significantly increased(P<0.05).Conclusion:The research initially identifies the multi-component,multi-target,and multi-path mechanism of Kai-Xin-San in the treatment of depression.Kai-Xin-San may improve synaptic plasticity through calcium signaling pathway to exert antidepressant effects.

一步固相法合成锂离子电池高镍层状正极材料

高镍层状正极材料因其比容量高进而满足电动汽车的续航要求,是锂离子电池中占主导地位的正极材料之一。通常,商业化的高镍层状氧化物是由共沉淀前驱体合成的,而在共沉淀过程中需要对温度、pH、搅拌速率等条件的精确控制,以确保镍、钴和锰等阳离子的原子级混合。本文采用了简单的一步固相法成功合成了超高镍含量的层状氧化物材料。通过使用与目标产物具有相似层状结构的前驱体氢氧化镍,成功合成了LiNiO_(2)和LiNi_(x)Co_(y)O_(2)(x=0.85,0.9,0.95;x+y=1),其电化学性能可与共沉淀前驱体制备的高镍材料相媲美。通过XRD和XPS测试证实了Co掺杂到LiNiO_(2)中,并抑制了高镍氧化物中的锂镍混排。掺杂剂Co在提高高镍材料的放电容量、倍率性能和循环性能方面具有明显的优势。一步固相法为未来制备下一代高性能超高镍锂离子正极材料提供了一种简单有效制备方法。

我国全科和专科医生工作满意度现状和影响因素比较

医生工作满意度是医疗卫生行业健康发展的重要指标之一,严重影响医疗服务质量与患者就医体验。虽有诸多共同因素影响医生工作满意度,但现有研究显示,全科和专科两类不同执业特点的医生其工作满意度影响因素存在显著差别。本文从我国全科与专科医生工作满意度现状出发,梳理医生工作满意度研究证据,分析全科和专科医生工作满意度影响因素的异同,为改善医生工作满意度、促进医疗行业健康发展提出针对性政策建议。

Immunoregulation of KangAi injection combined with chemotherapy in advanced non-small cell lung cancer: a systematic review and meta-analysis

Objective: To evaluate the immunoregulation of KangAi (KA) injection combined with chemo-treatment (chemo) for Non-small cell lung cancer (NSCLC). Methods: We systematically searched the literature of PubMed, EMBASE, CENTRAL, MEDLINE, CNKI, Wanfang, and VIP databases for all Randomized controlled trials (published from the earliest possible year to January 2019, no language restrictions) comparing KA injection combined with chemo and chemo alone in patients with NSCLC. Our main endpoints were immune function, clinical efficiency, KPS score and adverse events. The Cochrane Risk of Bias tool was applied for quality assessment. Results: 11 studies involving 1060 participants were included. The immune function (MD=3.18, 95% CI: 0.98-4.00, P<0.00001), clinical response rate (RR=1.28, 95%CI: 1.17-1.40, P<0.00001), KPS score (RR=1.86, 95%CI: 1.35-2.57, P=0.0002), and adverse events (RR=0.57, 95%CI: 0.50-0.65, P<0.00001) in the group of KA injection plus Chemo were vastly different from those in Chemo alone. Conclusion: KA injection combined with Chemo in the treatment of NSCLC improved the immune function, clinical efficiency and safety compared to Chemo alone. However, because many of the methodologies included in randomized controlled trials are of poor quality, more rigorous design and large randomized controlled trials are needed to test this benefit.

Ethanol-assisted synthesis of a Ni single-atom catalyst with poriferous 3D framework for efficient cascade CO_(2)electroreduction

The electroreduction of carbon dioxide to generate multicarbon products is significant for achieving a carbon-neutral economy.However,the selectivity for multi-carbon products faces several challenges,such as the intricate nature of the multistep hydrogenation processes,slow reaction kinetics and the bicarbonate precipitate issue caused by alkaline conditions.These factors hinder the extensive utilization of this reaction.Herein,we successfully developed and implemented a tandem electrolyzer cascade to separate and optimize the complex elementary reactions involved in the process of multi-carbon production.

Northeastern Asia humidification at the end of the Miocene drives the boost of mammalian dispersals from the Old to New World

Mammals have high dispersal ability,and many lineages can spread across the continents when a landbridge appears.Here,we summarize the dispersal of mammals between the Old and New World at the end of the Miocene.Our analysis suggested that the three phases of dispersal represented the largest dispersal tide during the Neogene,and the direction of dispersal is dominated by being from the Old to New World.Judging from the components that crossed the dispersal corridor,the Arctic environment near the Beringia corridor in the first phase(~7.5 Ma)is a mixed environment,and in the second phase(~6.5 Ma)is an open environment,and in the third phase(~5.8 Ma and continue to the Pliocene)is a wooded(closed)environment.A clear trend of eastern Asian humidification driven by Asian monsoon and the global C4 grassland expansion explain this dispersal pattern.The boost of mammalian dispersals is controlled by the heterogeneity of environmental changes in different continents.

High-frequency ultrasound features of basal cell carcinoma and its association with histological recurrence risk

Background: Due to advances in high-frequency ultrasound technology, it is easier to detect fine structures of skin lesions. The aim of this study was to examine the ultrasonographic features and use recurrence risk stratification to assess the diagnostic performance of pre-operative ultrasound examination of basal cell carcinoma (BCC). Methods: This was a retrospective study. Forty-six BCC lesions underwent pre-operative ultrasound examination using 50- and 20- MHz probes. Ultrasonographic shape, margin, internal echoes, hyper-echoic spots, posterior echoes, and depth of the lesion were evaluated and correlated with the risk of recurrence based on histological features. Results: Forty-two patients had 46 skin lesions in total. The high-risk (n = 6) and low-risk (n = 40) groups exhibited considerable overlap in the ultrasonographic manifestations and no significant difference in margin (χ^2 = 3.231, P = 0.072), internal echo (χ^2 = 1.592, P = 0.207), or posterior echo (P = 0.169). However, high-risk BCCs tended to be irregular in shape than low-risk lesions (χ^2 = 4.313, P = 0.038). Both types presented hyper-echoic spots (χ^2 = 1.850, P = 0.174). Additionally, 78% of low-risk lesions were confined to the dermis (31/40), and 100% of high-risk lesions infiltrated into the sub-cutaneous tissue, resulting in a significant difference between the two groups (χ^2 = 10.951, P = 0.001). Ultrasound detected sub-clinical lesions in five patients. Conclusions: High-frequency ultrasound can provide important information for pre-operative evaluation of risk in BCC foci and reveal hidden lesions. The technique may play a crucial role in guiding therapeutic options for BCC.

Deep learning-based,computer-aided classifier developed with dermoscopic images shows comparable performance to 164 dermatologists in cutaneous disease diagnosis in the Chinese population

Background:Diagnoses of Skin diseases are frequently delayed in China due to lack of dermatologists.A deep learning-based diagnosis supporting system can facilitate pre-screening patients to prioritize dermatologists’efforts.We aimed to evaluate the classification sensitivity and specificity of deep learning models to classify skin tumors and psoriasis for Chinese population with a modest number of dermoscopic images.Methods:We developed a convolutional neural network(CNN)based on two datasets from a consecutive series of patients who underwent the dermoscopy in the clinic of the Department of Dermatology,Peking Union Medical College Hospital,between 2016 and 2018,prospectively.In order to evaluate the feasibility of the algorithm,we used two datasets.Dataset I consisted of 7192 dermoscopic images for a multi-class model to differentiate three most common skin tumors and other diseases.Dataset II consisted of 3115 dermoscopic images for a two-class model to classify psoriasis from other inflammatory diseases.We compared the performance of CNN with 164 dermatologists in a reader study with 130 dermoscopic images.The experts’consensus was used as the reference standard except for the cases of basal cell carcinoma(BCC),which were all confirmed by histopathology.Results:The accuracies of multi-class and two-class models were 81.49%±0.88%and 77.02%±1.81%,respectively.In the reader study,for the multi-class tasks,the diagnosis sensitivity and specificity of 164 dermatologists were 0.770 and 0.962 for BCC,0.807 and 0.897 for melanocytic nevus,0.624 and 0.976 for seborrheic keratosis,0.939 and 0.875 for the"others"group,respectively;the diagnosis sensitivity and specificity of multi-class CNN were 0.800 and 1.000 for BCC,0.800 and 0.840 for melanocytic nevus,0.850 and 0.940 for seborrheic keratosis,0.750 and 0.940 for the"others"group,respectively.For the two-class tasks,the sensitivity and specificity of dermatologists and CNN for classifying psoriasis were 0.872 and 0.838,1.000 and 0.605,respectively.Both the dermatologists and CNN achieved at least moderate consistency with the reference standard,and there was no significant difference in Kappa coefficients between them(P>0.05).Conclusions:The performance of CNN developed with relatively modest number of dermoscopic images of skin tumors and psoriasis for Chinese population is comparable with 164 dermatologists.These two models could be used for screening in patients suspected with skin tumors and psoriasis respectively in primary care hospital.

Fossil evidence reveals uplift of the central Tibetan Plateau and differentiated ecosystems during the Late Oligocene

The uplift of different parts of the Tibetan Plateau caused by the collision,subduction and thickening of the Indian-Eurasian continent is considered to be the most significant landform change of Asia in the last 50 Ma.The plateau uplift led to elevation and topographical changes in neighboring areas and created diversified niches for the distribution and migration of plants and animals.The resultant high mountains controlled the South Asian monsoon,preventing the monsoon from crossing the plateau and reaching the hinterland of Asia.

Recent progress on high-entropy materials for electrocatalytic water splitting applications

Advanced materials for electrocatalytic water splitting applications have been sought-after considering both environmental and economic requirements.However,the traditional materials design concept limits the exploration of high-performance catalysts.The born of a materials design concept based on multiple elements,high-entropy materials,provides a promising path to break the shackles of compositional design in materials science.A number of high-entropy materials were reported to show remarkable properties for electrocatalytic water splitting applications.High-entropy materials were widely confirmed to be one kind of the best electrocatalysts for water splitting applications.Due to the synergy of multiple metal components,they show excellent catalytic activity.Several nontraditional methods were developed and reported to prepare high-performance high-entropy materials.This review article presents the recent progress on high-entropy materials for electrocatalytic water splitting applications.Moreover,it presents the research interests and future prospects in this field.

Bridging the knowledge gap on the evolution of the Asian monsoon during 26–16 Ma

The evolution of the Asian monsoon from the Late Oligocene to the Early Miocene is poorly understood.Here,we first reconstruct the precipitation data of central Tibet during 26–16 million years ago(Ma),applying the coexistence approach to sedimentary pollen data,and detect an intensified Asian monsoon with
1.35 Ma and
0.33 Ma cycles.Paleoclimate modeling is used to show the importance of paleogeographic location in the development of the paleomonsoon.In addition,the results of spectral analysis suggest that the fluctuations in the Asian monsoon during 26–16 Ma can be attributed to the long-period cyclicities in obliquity(
1.2 Ma).These findings provide climate data that can be used to understand the Asian monsoon evolution during the Late Oligocene to Early Miocene and highlight the effects of paleogeographic patterns and long-period orbital forcings on the tectonic-scale evolution of the Asian monsoon.

Dermoscopic Features of Basal Cell Carcinoma and Their Association with Histological Types in A Chinese Population:A Perspective Study

Objective:The treatments and prognoses of high-risk and low-risk basal cell carcinomas are quite different.This study aimed to examine the dermoscopic features of basal cell carcinomas and assess the association between the features and basal cell carcinomas recurrence risks in a Chinese population.Methods:Patients with histopathologically confirmed basal cell carcinomas examined from March 2016 to April 2020 were enrolled.The dermoscopic features were evaluated,and the correlations between these features and the histological types and recurrence risks were assessed.Results:The study cohort comprised 119 Chinese patients with a total of 119 skin lesions.The most common dermoscopic feature of basal cell carcinomas was the absence of a pigment network(119/119,100%),followed by shiny white streaks(105/119,88.24%),blue-gray ovoid nests(99/119,83.19%),multiple blue globules(78/119,65.55%),and arborizing vessels(78/119,65.55%);yellow-white structures were present in 29/119 lesions(24.37%).Leaf-like and spoke-wheel areas were significantly associated with superficial basal cell carcinomas(P<0.001),while arborizing vessels(P<0.001),blue-gray ovoid nests(P<0.001),and ulceration(P<0.05)were significantly associated with nonsuperficial basal cell carcinomas subtypes.The dermoscopic features of the high-risk and low-risk groups exhibited considerable overlap;however,the respective independent predictive factors for a high and low risk of basal cell carcinomas recurrence were short fine telangiectases(P<0.05)and blue-gray ovoid nests(P<0.05).Conclusion:Dermoscopy provides important information about basal cell carcinomas and is helpful in differentiating superficial basal cell carcinomas from other subtypes.The dermoscopic vascular structures and bluegray ovoid nests play a crucial role in evaluating the basal cell carcinomas risks preoperatively.