α-Synuclein pathology from the body to the brain:so many seeds so close to the central soil

α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.

Loose Body in the Knee Joint: A Case Report

Background: Loose bodies (LBs) within the knee joint are commonly encountered during clinical practice and are frequently observed during knee arthroscopy. The primary treatment involves the removal of loose bodies;however, their complete eradication is often challenging and may not address underlying diseases, leading to persistent symptoms and the risk of new loose body formation. Aim: This case report aims to present the findings and surgical management of a 52-year-old male with an unusually large osseous loose body in the knee joint and associated pathologies. Case Presentation: The patient, a 52-year-old male, experienced recurrent episodes of severe, sudden, and painful locking of the knee joint, leading to difficulties moving. A plain MRI study was conducted to evaluate the condition of the knee joint, which revealed various degenerative changes and the presence of a loose body. Subsequently, an arthroscopic examination was performed under general anesthesia, uncovering the presence of an abnormally large loose body, as well as other pathologies including chondropathy, meniscal degeneration, and Baker’s cyst. Conclusion: Loose bodies (LBs) in the knee joint pose significant challenges and may lead to debilitating symptoms. Timely diagnosis and appropriate surgical intervention are crucial for symptom relief and the prevention of further joint damage as arthroscopic excision. Comprehensive imaging has a vital role in guiding treatment decisions and optimizing patient outcomes. In this case, the removal of the loose body improved patient outcomes and helped prevent potential joint complications.

Writing the Silenced Female Body, Scrutinizing the Grand Narrative of Colonization and Decolonization: The Body in Zoë Wicomb’s David’s Story

David’s Story by Zoë Wicomb addresses the complexities of representing female suffering and the limitations of traditional historical narratives in capturing the experiences of marginalized bodies.It challenges the grand narratives of national history by emphasizing the indispensable role of women’s experiences.Through characters like Dulcie and Rachael,Wicomb portrays the female body as a site of resistance and resilience,highlighting the need for more nuanced and inclusive ways of documenting history.Underscoring the inexpressibility of trauma and the limitations of language and representation,the novel self-reflexively acknowledges its own aporia of completing the narrative,embodying the ongoing struggle to capture the full breadth of human experience.

A novel binary effective medium model to describe the prepeak stressstrain relationship of combined bodies of rock-like material and rock

Combined bodies of rock-like material and rock are widely encountered in geotechnical engineering,such as tunnels and mines.The existing theoretical models describing the stress-strain relationship of a combined body lack a binary feature.Based on effective medium theory,this paper presents the governing equation of the“elastic modulus”for combined and single bodies under triaxial compressive tests.A binary effective medium model is then established.Based on the compressive experiment of concretegranite combined bodies,the feasibility of determining the stress threshold based on crack axial strain is discussed,and the model is verified.The model is further extended to coal-rock combined bodies of more diverse types,and the variation laws of the compressive mechanical parameters are then discussed.The results show that the fitting accuracy of the model with the experimental curves of the concretegranite combined bodies and various types of coal-rock combined bodies are over 95%.The crack axial strain method can replace the crack volumetric strain method,which clarifies the physical meanings of the model parameters.The variation laws of matrix parameters and crack parameters are discussed in depth and are expected to be more widely used in geotechnical engineering.

Joint Detection of Serum Vitamin D,Body Mass Index,and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn’s Disease

Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.

Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.

Association between childhood obesity and gut microbiota:16S rRNA gene sequencing-based cohort study

BACKGROUND This study aimed to identify characteristic gut genera in obese and normal-weight children(8-12 years old)using 16S rDNA sequencing.The research aimed to provide insights for mechanistic studies and prevention strategies for childhood obesity.Thirty normal-weight and thirty age-and sex-matched obese children were included.Questionnaires and body measurements were collected,and fecal samples underwent 16S rDNA sequencing.Significant differences in body mass index(BMI)and body-fat percentage were observed between the groups.Analysis of gut microbiota diversity revealed lowerα-diversity in obese children.Differences in gut microbiota composition were found between the two groups.Prevotella and Firmicutes were more abundant in the obese group,while Bacteroides and Sanguibacteroides were more prevalent in the control group.AIM To identify the characteristic gut genera in obese and normal-weight children(8-12-year-old)using 16S rDNA sequencing,and provide a basis for subsequent mechanistic studies and prevention strategies for childhood obesity.METHODS Thirty each normal-weight,1:1 matched for age and sex,and obese children,with an obese status from 2020 to 2022,were included in the control and obese groups,respectively.Basic information was collected through questionnaires and body measurements were obtained from both obese and normal-weight children.Fecal samples were collected from both groups and subjected to 16S rDNA sequencing using an Illumina MiSeq sequencing platform for gut microbiota diversity analysis.RESULTS Significant differences in BMI and body-fat percentage were observed between the two groups.The Ace and Chao1 indices were significantly lower in the obese group than those in the control group,whereas differences were not significant in the Shannon and Simpson indices.Kruskal-Wallis tests indicated significant differences in unweighted and weighted UniFrac distances between the gut microbiota of normal-weight and obese children(P<0.01),suggesting substantial disparities in both the species and quantity of gut microbiota between the two groups.Prevotella,Firmicutes,Bacteroides,and Sanguibacteroides were more abundant in the obese and control groups,respectively.Heatmap results demonstrated significant differences in the gut microbiota composition between obese and normal-weight children.CONCLUSION Obese children exhibited lowerα-diversity in their gut microbiota than did the normal-weight children.Significant differences were observed in the composition of gut microbiota between obese and normal-weight children.

Striatal oxidative damages and neuroinflammation correlate with progression and survival of Lewy body and Alzheimer diseases

Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas.The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated.In this observational study,we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases(LBDs)and Alzheimer disease(AD),shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration.We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival.Disease progression in LBDs correlated positively with poly(ADP-Ribose)and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts,indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes.Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxo-d G)and myeloperoxidase concentrations in the striatum,suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism ofβ-amyloid entering the mitochondria and subsequent free radicals generation.Patients with lower striatal 8-oxo-d G and myeloperoxidase levels had a survival advantage in AD.The age of onset also affected disease progression.Tissue requests for the postmortem biochemistry,genetics,and autoradiography studies were approved by the Washington University Alzheimer's Disease Research Center(ADRC)Biospecimens Committee(ethics approval reference number:T1705,approval date:August 6,2019).Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health&Safety Biological Safety Committee(approval code:3739,approval date:February 25,2020).Radioactive Material Authorization was approved by the Washington University Environmental Health&Safety Radiation Safety Committee(approval code:1056,approval date:September 18,2019).

Colliding Bodies Optimization with Machine Learning Based Parkinson’s Disease Diagnosis

Parkinson’s disease(PD)is one of the primary vital degenerative diseases that affect the Central Nervous System among elderly patients.It affect their quality of life drastically and millions of seniors are diagnosed with PD every year worldwide.Several models have been presented earlier to detect the PD using various types of measurement data like speech,gait patterns,etc.Early identification of PD is important owing to the fact that the patient can offer important details which helps in slowing down the progress of PD.The recently-emerging Deep Learning(DL)models can leverage the past data to detect and classify PD.With this motivation,the current study develops a novel Colliding Bodies Optimization Algorithm with Optimal Kernel Extreme Learning Machine(CBO-OKELM)for diagnosis and classification of PD.The goal of the proposed CBO-OKELM technique is to identify whether PD exists or not.CBO-OKELM technique involves the design of Colliding Bodies Optimization-based Feature Selection(CBO-FS)technique for optimal subset of features.In addition,Water Strider Algorithm(WSA)with Kernel Extreme Learning Machine(KELM)model is also developed for the classification of PD.CBO algorithm is used to elect the optimal set of fea-tures whereas WSA is utilized for parameter tuning of KELM model which alto-gether helps in accomplishing the maximum PD diagnostic performance.The experimental analysis was conducted for CBO-OKELM technique against four benchmark datasets and the model portrayed better performance such as 95.68%,96.34%,92.49%,and 92.36%on Speech PD,Voice PD,Hand PD Mean-der,and Hand PD Spiral datasets respectively.

基于线性密集台阵的2023年甘肃积石山M_(S)6.2地震断层低速带研究

2023年12月18日,甘肃省积石山县发生M_(S)6.2逆冲型地震。该地震发生在祁连活动地块拉脊山北缘断裂带,在断裂两侧曾发生过20余次5级左右中强地震,地震活动频次高,因此研究拉脊山断裂带特征具有重要意义。根据拉脊山断裂走向和此次地震余震分布,在刘集乡布设一条线性密集台阵,利用不同方位的余震事件计算体波的走时延时和放大效应。结果表明,P波和S波分别存在6个采样点(约0.012 s)和15个采样点(约0.03 s)的走时延时,推断出台阵西侧存在一个约150 m宽近似垂直的断层低速带,且该结果与远震P波相似性系数矩阵结果一致。

Development and validation of a screening instrument for cognitive fluctuation in patientswith neurocognitive disorder with Lewy bodies(NCDLB):the Mayo Fluctuations Scale-Thai version

Background Prevalence of neurocognitive disorder with Lewy bodies （NCDLB） is low in Asian populations, which may partially refect its diagnostic diffculty. The Mayo Fluctuations Scale, a short questionnaire that evaluates cognitive fuctuation, has been shown to signifcantly differentiate NCDLB from Alzheimer＇s disease.Aim This study aimed to develop the Mayo Fluctuations Scale-Thai version and assess its validity to screen NCDLB in an elderly population.Methods The Mayo Fluctuations Scale was translated into Thai. The process involved back-translation, cross-cultural adaptation, feld testing of the prefnal version, as well as fnal adjustments. From all patients attending the Psychiatric and Memory Clinic at Ramathibodi Hospital, 135 patients accompanied by their primary caregivers were included. Caregivers were interviewed by research assistants using a four-item scale, and psychiatrists determined patients＇ diagnosis based on the diagnostic and statistical manual of mental disorders （DSM）-5 criteria. Evaluations performed by psychiatrists and research assistants were blinded.Results Seventeen participants had been diagnosed with major NCDLB. At a cut-off score of 2 or over, the Mayo Fluctuations Scale exhibited excellent performance to differentiate major NCDLB from other major neurocognitive disorders （NCDs）, with a sensitivity of 94.1% and a specifcity of 71.4%, and acceptable performance to differentiate mild NCDLB from other mild NCDs, with a sensitivity of 60% and a specifcity of 93.1%.Conclusion The Mayo Fluctuations Scale-Thai version is an excellent screening tool for major NCDLB and an acceptable tool that may be used with other additional tests for mild NCDLB. The tool is practical for use in memory and psychiatric clinics. Further validation studies in participants with other specifc clinical conditions are required.

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

Dementia is mainly a neurodegenerative disorder involved in several systems, including central nervous system, endocrinology/metabolism system and circulatory system. Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the most common forms of the dementia, accounting for 60% - 80% and 10% - 20% of all cases, respectively. DLB is defined by widespread neocortical, limbic and brainstem Lewy bodies but frequently accompanied by variable levels of AD pathology. This pathological and clinical overlap makes their differential diagnosis complicated. Recent advances in the identification of disease bio-markers now make it possible to detect and distinguish their pathology in the early or preclinical stage of the diseases, even in cognitively normal individuals. In addition to the key biomarkers (amyloid β or Aβ, tau and α-synuclein), neurotrophins such as cocaine- and amphetamine-regulated transcript (CART) have also drawn attention due to their expressions and functions. This article summarizes the progress in the definition, pathology and diagnosis of dementia, with a focus on potential biochemical markers in the cere-brospinal fluid (CSF) in the differential diagnosis of the main forms of dementia. To prediction or early diagnosis of dementia, the role of specific and sensitive CSF biomarkers seems to be crucial in a routine clinical setting. The concerns and challenges in the biomarker field are also discussed.

Correlation between Alzheimer’s Disease and Dementia with Lewy Bodies Scores Using VSRAD Advance

The objective of the study was to explore the relationship between the indicators of Alzheimer’s disease and dementia with Lewy bodies using the voxel-based specific regional analysis system for Alzheimer’s Disease (VSRAD) advance. Among 36 patients with suspected dementia, patients with Alzheimer’s disease and dementia with Lewy bodies were identified using VSRAD advance from March 1 to October 30, 2019. All patients underwent brain Magnetic Resonance Imaging (MRI). We diagnosed Alzheimer’s disease using Volume of Interest (VOI) in the Medial Temporal Lobe (MTL) atrophy ratio > 2 and dementia with Lewy bodies using both VOI in the MTL atrophy ratio ≤ 2 and gray/white matter atrophy ratio ≥ 0.2. The correlation between the indicators of Alzheimer’s disease and dementia with Lewy bodies was calculated. The number of patients classified as having Alzheimer’s disease and dementia with Lewy bodies was 25 and 11, respectively. In the Alzheimer’s disease group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem gray matter was r = -0.40 (p = 0.045). In dementia with Lewy bodies group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem white matter was r = -0.78 (p < 0.01). Using VSRAD advance, gray matter atrophy and dorsal brainstem grey/white matter atrophy were found to be negatively correlated in Alzheimer’s disease and dementia with Lewy bodies.

鄂北S井区盒8上亚段砂体叠置类型及其对气藏分布的影响

为明确鄂北S井区盒8上亚段地层砂体叠置类型及其与气藏分布的关系,通过岩心观察、测井解释等方法对研究区盒8上亚段沉积微相类型、砂体的垂向叠置及侧向接触关系进行深入研究,再结合试气资料探讨不同砂体叠置类型的气藏分布特征。结果表明:鄂北S井区盒8上亚段为曲流河三角洲平原亚相,有利砂体对应的沉积微相类型为边滩与河道充填微相;砂体垂向叠置类型可划分为分离式、叠加式、切叠式、替代式,侧向接触关系可划分为间湾接触、堤岸接触、对接式、侧切式、替代式;鄂北S井区盒8上亚段砂体垂向叠置类型主要为侧向切叠式和替代式,增加了砂体在侧向上的连通性;盒8上亚段砂体侧向接触关系主要为侧切式,提升了砂体侧向上的连通程度,气藏储存关系较好;单一、孤立存在的砂体,其连通性较差,整体的含气性也较差。该研究对寻找低渗透背景下产能高、潜力大的砂体分布区具有重要指导意义。

肺岩宁颗粒干预细胞周期G_1/S检测点调控信号抗Lewis肺癌细胞增殖的研究

目的观察肺岩宁颗粒对Lewis肺癌小鼠肿瘤生长、肿瘤细胞周期分布,以及G1/S检测点调控信号RB-E2F1生物轴的影响。方法采用C57BL/6小鼠,造模并随机分为6组:模型组、顺铂组、肺岩宁煎剂组(煎剂组)、肺岩宁颗粒低剂量组(低剂量组,0·3g)、肺岩宁颗粒中剂量组(中剂量组,0·6g)、肺岩宁颗粒高剂量组(高剂量组,1·2g)。造模后顺铂组1、3、5天腹腔注射顺铂0·1mg,其他各组分别灌胃给药14天,观察各组治疗后抑瘤率、瘤重、体重,流式细胞术检测细胞周期时相分布,RT-PCR测定肿瘤组织视网膜母细胞瘤蛋白(RB)-腺病毒E2启动子结合转录因子(E2F1)的mRNA表达,Western blot检测RB、E2F1蛋白表达。结果各用药组瘤重低于模型组(P<0·05,P<0·01),中剂量组体重明显高于模型组和顺铂组(P<0·05,P<0·01)。流式细胞术发现中剂量组的G0/G1比例较模型组、顺铂组和煎剂组显著增多(P<0·01),癌细胞增殖指数明显降低(P<0·01,P<0·05)。RT-PCR显示中剂量组E2F1mRNA水平明显低于模型组、顺铂组和煎剂组(P<0·01);中剂量组RBmRNA表达明显高于模型组、顺铂组和煎剂组(P<0·01)。Western blot分析显示中剂量组较模型组和顺铂组明显抑制E2F1蛋白表达(P<0·05),并较模型组、顺铂组和煎剂组明显增加RB蛋白表达(P<0·05)。结论肺岩宁颗粒抑制Lewis肺癌肿瘤生长与干预细胞周期时相分布有关,能使癌细胞较多的阻滞在细胞周期G0/G1期,通过抑制E2F1,增强RB表达,从而干预细胞周期G1/S检测点信号通路中RB-E2F1生物轴实现抗肺癌增殖。

应用蛋白酶体抑制剂Lactacystin建立有Lewy体的帕金森病大鼠模型

目的建立符合帕金森病(PD)病理特征———黑质细胞有Lewy体的PD大鼠模型。方法分别在大鼠一侧黑质致密部注射蛋白酶体抑制剂Lactacystin8mg(Lactacystin组)、等体积生理盐水(NS组)和6-羟基多巴胺(6-OHDA组)12mg;观察大鼠自主行为和阿朴吗啡诱导的旋转行为;光镜下观察中脑组织学改变;应用免疫组化染色观察黑质细胞α-synuclein表达和酪氨酸羟化酶(TH)阳性细胞数;测定纹状体区多巴胺和高香草酸含量。结果NS组大鼠未见行为异常;Lactacystin组大鼠出现进行性的运动迟缓、少动、震颤、头向健侧倾斜,注射阿朴吗啡后出现向健侧旋转运动;给药后3周黑质部TH阳性细胞数较NS组减少了83.29%(P<0.01),部分黑质细胞内出现α-synuclein免疫反应呈强阳性的Lewy体;纹状体多巴胺和高香草酸含量(154.82±37.17,98.66±18.81)较NS组明显减少(822.87±131.25,617.77±95.74)(均P<0.01);6-OHDA组大鼠出现与Lactacystin组类似的行为变化,黑质细胞亦显著减少,但未见Lewy体。结论利用蛋白酶体抑制剂Lactacystin阻碍α-synuclein的降解可以建立有Lewy体的PD大鼠模型。

榄香烯乳联合化疗对小鼠Lewis肺癌组织S100A4及MMP-9蛋白表达的影响

【目的】观察榄香烯乳联合化疗对Lewis肺癌的抑瘤作用及其对S100A4及MMP-9表达的影响,探讨其作用机制。【方法】将24只接种Lewis肺癌瘤株的C57BL/6小鼠随机分为肺癌模型组、化疗组、榄香烯乳组、榄香烯乳联合化疗组,每组6只。接种后第11天开始给药治疗,化疗组给予小鼠腹腔注射足叶乙甙(3 mg·kg^(-1)·d^(-1))、顺铂(3 mg·kg^(-1)·d^(-1)),榄香烯乳组给予小鼠腹腔注射榄香烯乳(100 mg·kg^(-1)·d^(-1)),榄香烯乳联合化疗组小鼠腹腔注给予射榄香烯乳(100 mg·kg^(-1)·d^(-1))、足叶乙甙(3 mg·kg^(-1)·d^(-1))、顺铂(3 mg·kg^(-1)·d^(-1))。连续给药7 d后,观察各组小鼠瘤体质量,脾脏、胸腺指数变化,计算抑瘤率及抑制转移率,采用酶联免疫吸附(ELISA)法检测瘤组织中S100A4蛋白和基质金属蛋白酶-9(MMP-9)含量,采用免疫组化法检测瘤组织中S100A4和MMP-9蛋白表达。【结果】与化疗组比较,榄香烯乳联合化疗组抑瘤率及抑制转移率均明显升高,肺癌小鼠脾脏指数、胸腺指数显著增加,瘤组织中S100A4和MMP-9含量明显降低,S100A4和MMP-9蛋白阳性表达率降低明显(P<0.05或P<0.01)。【结论】榄香烯乳联合化疗可抑制小鼠Lewis肺癌的生长转移,其机制可能与降低癌组织中S100A4、MMP-9蛋白的表达有关。

bFGF单抗协同替吉奥抑制肺癌Lewis细胞的增殖及移植瘤血管新生

目的:探讨碱性成纤维生长因子(basic fibroblast growth factor,bFGF)单抗与替吉奥(gimeracil and oteracil porassi-um,又称S-1)联合应用体内外抑制小鼠Lewis肺癌细胞增殖、移植瘤生长及转移、肿瘤血管新生的协同作用。方法:CCK-8法检测bFGF单抗及S-1对Lewis细胞增殖的抑制作用。建立C57BL/6小鼠Lewis肺癌自发转移瘤模型,32只小鼠随机分成生理盐水(NS)组、bFGF单抗组、S-1组和bFGF单抗+S-1组,每组8只;测量瘤体,绘制生长曲线,称瘤质量并计算抑瘤率;计数各组肺表面转移瘤结节;CD31标记血管内皮细胞,计数转移瘤微血管密度(microvessel density,MVD)。结果:bFGF单抗、S-1剂量依赖性抑制Lewis细胞增殖(P<0.05),联合用药组抑制率明显高于单药组(P<0.05或P<0.01)。bFGF单抗组、S-1组以及bFGF单抗+S-1组对Lewis转移瘤的抑瘤率分别为37.8%、47.7%、65.9%,联合组抑瘤率明显高于单药组(P<0.05或P<0.01)。联合组肺表面转移结节、微血管密度明显低于单药组(2.71±0.76vs6.57±0.98、4.71±0.76;21.6±2.9vs33.4±4.9、41.9±6.3;P<0.05或P<0.01)。结论:bFGF单抗联合S-1对Lewis肺癌移植瘤具有协同抑制作用,其机制与抑制细胞增殖及血管新生有关。

Lewis酸引发的1，3－戊二烯阳离子聚合

以ＡｌＣｌ_３、ＢＦ_３·ＯＥｔ_２、ＴｉＣｌ_４和ＡｌＢｒ_３等Ｌｅｗｉｓ酸为引发剂，在不同溶剂中（正己烷、二氯甲烷、甲苯）于３０℃引发１，３－戊二烯阳离子聚合。实验结果表明，ＡｌＣｌ_３和ＢＦ_３·ＯＥｔ_２显示出较高的催化活性，ＡｌＣｌ_３引发的聚合反应得到的聚合物具有较高的分子量，但聚合反应过程中总是伴随交联产物的生成。用甲苯作溶剂时交联反应可以被抑制。ＩＲ和￣１ＨＮＭＲ结果表明，甲苯作为聚合反应的链转移剂参与了链转移反应。

芪加合剂对小鼠Lewis肺癌的抑制作用

目的 研究芪加合剂对小鼠 Ｌｅｗｉｓ 肺癌的影响。方法 观察 Ｌｅｗｉｓ 肺癌小鼠的生存时间和瘤重。结果 芪加合剂（１３７５ ～２７５０ ｇ·ｋｇ － １） 治疗或预防给药均能延长 Ｌｅｗｉｓ肺癌小鼠平均生存时间；对小鼠 Ｌｅｗｉｓ 肺癌瘤重增长有明显抑制作用，并可抑制其自发性肺转移。结论 芪加合剂对肺癌可能具有明显抑制作用。