Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody

AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

Prokaryotic Expression of Rubber Elongation Factor Gene and Preparation of Its Polyclonal Antibody

[Objective] The aim of this study was to prepare the recombination protein of rubber elongation factor and its polyclonal antibodies.[Method] The encoding gene of rubber elongation factor(REF)was amplified by RT-PCR,and cloned into the prokaryotic expression vector pDEST17 to transform into Escherichia coil BI2I-AI.The recombinant protein induced by L-Arabinose was purified by the affinity chromatography.As the immunogen,the recombination protein was used to immunize mice for preparing polyclonal antibodies,while ELISA and Western blot hybridization were used to detect the titers and specificity.[Result] The purified recombination protein of REF with high expression was used to immunize house mice for preparing polyclonal antibodies with high titer and specificity.The western blot hybridization showed that the antibody could recognize the natural REF from latex.[Conclusion] The recombination protein of REF was successfully obtained and the mouse anti REF antibody with high titer and specificity was prepared,which lays a basis for further studies on biological functions of rubber elongation factor and other membrane proteins in rubber particles.

Transforming growth factor -β neutralizing antibodies inhibit subretinal fibrosis in a mouse model

AIM:To determine the involvement of the transforming growth factor(TGF)-β with the development of experimental subretinal fibrosis in a mouse model.· METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells(PECs) and the local expression of TGF-β isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA) at various time points.In addition,we investigated the effect of TFG-β-neutralizing antibodies(TGF-β NAb) on subretinal fibrosis development.· RESULTS:TGF-β1 and TGF-β2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5,reaching the peak.TGF-β3 mRNA was not detected in the present study.The result of ELSIA showed that active TGF-β1 and TGF-β2 levels were upregulated to 10-fold approximately,while total TGF-β1 and TGF-β2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with na?觙ve mice at day 5.TGF-β NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7.· CONCLUSION:Our results indicate that TGF-β signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-β inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.·

Anti-cytomegalovirus antibodies and other atherosclerosis risk factors in patients with cardiovascular diseases

Objective To determine anti-cytomegalovirus(CMV) antibodies along with anti-Chlamydia pneumoniae(CP) antibodies in comparison with inflammatory markers and other risk factors of atherosclerosis in patients with selected cardiovascular diseases(CVD) . Methods A total of 228 patients with coronary heart disease(CHD) and/or hyperten-sion(HT) ,and those who underwent reconstructive vascular surgery(RVS) on carotids or abdominal aorta were tested for the presence of anti-CMV IgG and IgM antibodies as well as for anti-CP IgA antibodies,C-reactive protein(CRP) ,and interleukin-6(IL-6) . Other risk factors for atherosclerosis,namely age,gender,smoking,hypercholesterolemia,and diabetes mellitus were also analyzed. Results Anti-CMV IgG antibodies were found in 204 patients sera(89.5%) ,compared with 46 positive of 68 sera in the controls(67.6%) ,whereas anti-CMV IgM antibodies were detected in 4 of 54 sera of patients tested(7.4%) ,but not in the controls. The highest proportion of positive sera with not only anti-CMV IgG antibodies(95.6.7%) ,but also anti-CP IgA antibodies(78.3%) ,IL-6(84.8%) and CRP(97.8%) ,was observed in patients with RVS. The results obtained corresponded to age,hypercholesterolemia,and diabetes. Conclusions The presence of anti-CMV antibodies together with antibodies to CP and markers of inflammation(CRP and IL-6) in our study was associated with CVD,primarily in elderly patients who underwent RVS.

Effects of two vectors on the expression of the NbNAC1 transcription factor and preparation of its polyclonal antibody

The NAC(NAM,ATAF,and CUC)superfamily is one of the largest plant-specific families containing transcription factors.An increasing number of studies suggest that NAC1 is involved in plants response to different biotic and abiotic stimulis.Nicotiana benthamiana is a widely used system for evaluating plant-pathogen interactions.In order to study the biochemical function of NbNAC1,NbNAC1 protein and antibody are essential.Therefore,we focused on developing a prokaryotic expression system for producing the Nicotiana benthamiana NbNAC1 protein of in Escherichia coli and the preparation of its polyclonal antibody.Firstly,we constructed two different molecular weight prokaryotic expression vectors:pGE vector with GST tag(pGEX4T-1–NbNAC1)and pET expression vector with His tag(pET28a-NbNAC1).The NbNAC1 protein can be successfully expressed in both vectors.The His-tagged NbNAC1 proteins are insoluble,while the GST-tagged NbNAC1 proteins are partially soluble.We then successfully purified and enriched both proteins.The His-tagged NbNAC1 was chosen to immunize rabbits owing to an unknown protein accompanying the GST-tagged NbNAC1.The anti-NbNAC1 polyclonal antibody had good specificity and could be used in subsequent protein-related studies.

Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease:Case series and review of literature

Anti-tumor necrosis factor(TNF) biologics are currentlyamongst the most widely used and efficacious therapies for inflammatory bowel disease(IBD). The development of therapeutic drug monitoring for infliximab and ada-limumab has allowed for measurement of drug levels and antidrug antibodies. This information can allow for manipulation of drug therapy and prediction of response. It has been shown that therapeutic anti-TNF drug levels are associated with maintenance of remission, and development of antidrug antibodies is predictive of loss of response. Studies suggest that a low level of drug antibodies, however, can at times be overcome by dose escalation of anti-TNF therapy or addition of an immunomodulator. We describe a retrospective case series of twelve IBD patients treated at the University of California-Irvine, who were on infliximab or adalimumab therapy and were found to have detectable but low-level antidrug antibodies. These patients underwent dose escalation of the drug or addition of an immunomodulator, with subsequent follow-up drug levels obtained. Eight of the twelve patients(75%) demonstrated resolution of antidrug antibodies, and were noted to have improvement in disease activity. Though data regarding overcoming low-level anti-TNF drug antibodies remains somewhat limited, cases described in the literature as well as our own experience suggest that this may be a viable strategy for preserving the use of an anti-TNF drug. Low-level anti-TNF drug antibodies may be overcome by dose escalation and/or addition of an immunomodulator, and can allow for clinical improvement in disease status. Therapeutic drug monitoring is an important tool to guide this strategy.

Monoclonal antibody for COVID-19: Unveiling the recipe of a new cocktail

The coronavirus disease 2019(COVID-19)pandemic has had a tremendous adverse impact on the global health system,public sector,and social aspects.It is unarguably the worst pandemic of the century.However,COVID-19 management is a mystery in front of us,and an authentic treatment is urgently needed.Various repurposed drugs,like ivermectin,remdesivir,tocilizumab,baricitinib,etc.,have been used to treat COVID-19,but none are promising.Antibody therapy and their combinations are emerging modalities for treating moderate COVID-19,and they have shown the potential to reduce hospitalisations.One antibody monotherapy,bamlanivimab,and two cocktails,casirivimab/imdevimab and bamlanivimab/esterivimab,have received authorization for emergency use by the United States Food and Drug Administration for the treatment of mild COVID-19 in high risk individuals.The European Emergency has made similar recommendations for use of the drug in COVID-19 patients without oxygen therapy.This brief review will focus on monoclonal antibodies and their combination cocktail therapy in managing COVID-19 infection.

益气养阴化痰祛瘀法对甲状腺机能亢进症激素抗体及氧化应激因子表达的影响

目的研究益气养阴化痰祛瘀法对甲状腺机能亢进症(Hyperthyroidism,简称甲亢)患者激素抗体和氧化应激因子表达的影响。方法选取2022年1月—2023年12月收治的76例甲亢患者,按照随机数字表法分组,对照组(38例)采用常规西药治疗,观察组(38例)在对照组基础上加用益气养阴化痰祛瘀方治疗;治疗2个月后对比两组临床疗效、中医证候积分、甲状腺功能(各项激素水平)、氧化应激因子、促甲状腺激素受体抗体(TRAb)、甲状腺过氧化物酶抗体(TPOAb)的表达。结果观察组治疗总有效率为94.74%(36/38),高于对照组(76.32%,29/38),差异有统计学意义(P<0.05)。治疗后,两组主症积分、次症积分和舌脉积分均降低,观察组低于对照组;两组促甲状腺激素(TSH)上升,游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)下降(P<0.05),观察组改善高于对照组;两组超氧化物歧化酶(SOD)升高,观察组SOD水平高于对照组,差异有统计学意义(P<0.05)。结论益气养阴化痰祛瘀法用于甲亢患者的治疗取得确切治疗成果,可以有效改善甲状腺功能,通过调控甲状腺激素水平、TRAb、TPOAb以及氧化应激因子的表达以改善病情,缓解症状。

输血实践中意外抗体阳性分布特点及高危因素回顾性分析

目的分析该院近年来输血患者中出现意外抗体阳性的情况,探讨其分布特点及其临床意义。方法收集该院2018年1月至2020年12月输注红细胞患者8417例,使用抗人球蛋白微柱卡法进行意外抗体筛查和特异性鉴定,并对其数据进行分析。结果输注红细胞8417例,意外抗体阳性37例,阳性占比为0.44%(37/8417)。分析ABO血型患者产生意外抗体的情况,可见AB型血型患者的意外抗体阳性率最高;不同ABO血型患者产生意外抗体阳性率和患者住院科室比较,差异有统计学意义(P<0.05);而组间输血史、妊娠史、年龄和男女比例差异无统计学意义(P>0.05)。意外抗体特异性阳性分布分析,发现Rh血型系统抗体(计算混合抗体)占比最高,达到48.60%;其次为自身抗体13.50%,冷抗体10.80%,MNS血型系统抗体5.40%,Lewis血型系统抗体5.40%,Kidd血型系统抗5.40%,其他特异性抗体(未鉴定出特异性)10.80%。单因素分析显示,意外抗体阳性患者性别间比较差异无统计学意义(P>0.05),而年龄、ABO血型、输血史、妊娠史、不同科室之间患者意外抗体阳性比例具有显著统计学意义(P<0.05)。二元Logistic回归分析显示有输血史、妊娠史、血液系统疾病、风湿免疫肾脏疾病和重症疾病是意外抗体检出的独立危险因素(P<0.05)。结论建议对输血患者在ABO和RhD血型同型输注的基础上,至少增加RhEc和RhE同型输注,将有效降低意外抗体的产生,促进临床用血安全。

贫血与非贫血孕妇Hb、VA、SF、Zn、IFA表达差异及相关性探究

目的探究贫血与非贫血孕妇血红蛋白(Hb)、维生素A(VA)、铁蛋白(SF)、锌(Zn)及内因子抗体(IFA)表达差异,并分析各指标表达与孕妇贫血的相关性。方法选取2022年8月至2023年4月我院收治的102例贫血孕妇为贫血组(Hb<110g/L),另选取同期102例非贫血孕妇为非贫血组,检测两组Hb、VA、SF、Zn、IFA表达水平,分析孕妇贫血的影响因素,将贫血组根据外周血Hb水平进行贫血程度划分[轻度(100g/L≤Hb<110g/L)、中度(70g/L≤Hb<99g/L)],比较不同贫血程度孕妇、不同孕期贫血孕妇Hb、VA、SF、Zn、IFA表达差异,分析Hb、VA、SF、Zn、IFA表达水平与贫血孕妇孕期、贫血程度的相关性,并分析Hb、VA、SF、Zn、IFA表达对中度贫血的预测价值。结果两组孕周、妊娠期合并症相比,差异有统计学意义(P<0.05);贫血组中度、轻度贫血孕妇Hb、VA、SF、Zn均低于非贫血组,IFA高于非贫血组(P<0.05),中度贫血孕妇Hb、VA、SF、Zn表达水平低于轻度贫血孕妇,IFA表达水平高于轻度贫血孕妇(P<0.05);不同孕期贫血孕妇Hb、VA、SF、Zn表达水平比较,孕晚期<孕中期<孕早期,IFA表达水平比较,孕早期<孕中期<孕晚期(P<0.05);Hb、VA、SF、Zn与贫血孕妇孕期、贫血程度呈负相关,IFA与贫血孕妇孕期、贫血程度呈正相关(P<0.05);孕周、妊娠期合并症、Hb、VA、SF、Zn、IFA是孕妇贫血的影响因素(P<0.05);Hb、VA、SF、Zn、IFA联合预测中度贫血的AUC为0.933,大于各参数单独预测(P<0.05)。结论贫血孕妇Hb、VA、SF、Zn、IFA表达明显异常,且Hb、VA、SF、Zn、IFA与贫血孕妇孕期、贫血程度联系密切,联合检测对预防孕妇中度贫血具有重要价值。

缺血性视网膜静脉阻塞继发黄斑水肿患者基线血清己糖激酶1抗体滴度与抗VEGF治疗后视力改善的相关性分析

目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗的53例患者,其中缺血性视网膜中央静脉阻塞(CRVO)23例(CRVO组),缺血性视网膜分支静脉阻塞(BRVO)30例(BRVO组)。另选取该院同期30例行超声乳化的白内障患者作为对照组。研究对象行基线血清己糖激酶1抗体滴度检测、眼科常规检查和光学相干断层成像(OCT)检查。所有RVO-ME患者按照“3+按需治疗方案(pro re nata,PRN)”向玻璃体内注射抗VEGF药物治疗。随访12个月,采用多元线性回归分析缺血性RVO-ME患者抗VEGF治疗后视力改善的影响因素。结果CRVO组基线logMAR BCVA高于对照组和BRVO组,CRVO组和BRVO组基线CRT、基线血清己糖激酶1抗体滴度高于对照组,且CRVO组基线CRT、基线血清己糖激酶1抗体滴度高于BRVO组,差异有统计学意义(P<0.05)。RVO-ME患者基线血清己糖激酶1抗体滴度与随访6个月(r=0.377,P=0.005)、9个月(r=0.362,P=0.008)和12个月(r=0.465,P<0.001)时BCVA改善呈正相关,与随访12个月时中断EZ横向长度减少值(r=0.401,P=0.001)呈正相关。多元线性回归分析结果显示,基线logMAR BCVA、基线血清己糖激酶1抗体滴度是缺血性RVO-ME患者抗VEGF治疗随访12个月时BCVA改善的影响因素(P<0.05)。结论己糖激酶1抗体作为一种新的血清生物标志物,与缺血性RVO-ME患者抗VEGF治疗后的视力改善相关。

类风湿因子亚型、抗CCP和抗RA33联合检测在早期类风湿关节炎诊断中的应用价值

目的探讨血清类风湿因子(RF)亚型(包括IgG-RF、IgA-RF、IgM-RF)、抗CCP、抗RA33联合检测在早期类风湿关节炎(RA)诊断中的意义。方法收集2021年6月至2022年5月医院收治的可疑RA患者作为研究对象,根据临床诊断结果将患者分为RA组(135例)和非RA组(1556例),测定两组血清IgG-RF、IgA-RF、IgM-RF、抗CCP、抗RA33水平,比较各项指标阳性表达情况,分析联合检测的诊断效能。结果RA组IgG-RF、IgA-RF、IgM-RF、抗CCP、抗RA33水平均高于非RA组(P<0.05);单项指标中,灵敏度和正确指数最高的是抗CCP,特异性最高的是IgG-RF;抗RA33灵敏度最低但特异性比较高。联合检测中以只要有阳性为判断标准,灵敏度和正确指数增加,灵敏度最高的是RF亚型/抗CCP/抗RA33(为99.26%),其次是RF亚型/抗CCP(95.56%);正确指数最高的是RF亚型/抗CCP/抗RA33(78.57%),其次是RF亚型/抗CCP(78.52%)。如果以联合检测中所有项目均阳性为判断标准,特异性明显升高,特异性最高的是RF亚型+抗CCP+抗RA33(99.55%),其次是RF亚型+抗RA33(98.78%)。结论RF亚型、抗CCP和抗RA33等指标对RA诊断具有一定价值,这些指标联合检测可以提高诊断灵敏度、特异性,提高早期诊断效能。

CDFI血流信号分级、抗CCP抗体、G6PI、RF对类风湿性关节炎的诊断价值

目的分析彩色多普勒血流显像(CDFI)血流信号分级、抗环瓜氨酸肽抗体(CCP)、葡萄糖6磷酸异构酶(G6PI)、类风湿因子(RF)对类风湿性关节炎(RA)的诊断价值。方法回顾性选取2022年4月至2023年10月新疆医科大学附属中医医院收治的100例RA患者纳入观察组,根据病情分为RA活动期组(n=50)和RA非活动期组(n=50);依据血流信号CDFI分级分为0~1级组(n=20)、2级组(n=17)、3级组(n=13)。选取同期本院收治的100例其他自身免疫性疾病患者纳入对照组。比较观察组、对照组一般临床资料(性别、病程、年龄、RA家族史、体重指数、吸烟史、饮酒史、居住地、职业等),比较不同活动期患者抗CCP抗体、G6PI及RF水平;比较不同血流信号分级组患者抗CCP抗体、G6PI及RF水平;采用受试者工作特征(ROC)曲线评估CDFI血流信号分级、抗CCP抗体、G6PI、RF联合检测对RA的诊断价值。结果两组患者性别构成比、病程、年龄、RA家族史、体重指数、吸烟史、饮酒史、居住地、职业比较,差异均无统计学意义(P>0.05);观察组患者抗CCP抗体、G6PI及RF水平均高于对照组,差异均有统计学意义(P<0.05)。RA活动期组患者抗CCP抗体、G6PI及RF水平均高于RA非活动期组患者,差异均有统计学意义(P<0.05)。血流信号3级组患者抗CCP抗体、G6PI及RF水平均高于血流信号0-1级组、2级组患者,差异均有统计学意义(P<0.05)。CDFI血流信号分级、抗CCP抗体、G6PI、RF单独检测RA的敏感度分别为79.57%、86.45%、82.14%、77.89%,特异度分别为83.89%、79.28%、83.67%、84.15%,AUC分别为0.855(0.804~0.907)、0.940(905~0.976)、0.893(0.852~0.935)、0.800(0.736~0.864),CDFI血流信号分级、抗CCP抗体、G6PI、RF联合检测RA的敏感度为89.36%,特异度为77.24%,AUC为0.957(0.933~0.980)。结论RA患者血清CCP抗体、G6PI、RF水平升高,随着CDFI血流信号分级增大,升高愈加明显,CDFI血流信号分级、抗CCP抗体、G6PI、RF联合检测RA诊断价值较高,对判断RA进展具有意义。

MDS患者反复输注血小板的输血效果及其影响因素分析

目的:探讨骨髓增生异常综合征(MDS)患者反复输注血小板的输血效果,并分析影响血小板输注无效(PTR)的因素。方法:选取2019年1月—2022年12月潍坊市中医院收治的63例MDS患者为此次研究对象。依据PTR判定标准[输血后24 h校正血小板增高指数值(CCI)≤4、血小板回升率(PPR)≤20%]评估入组对象输血效果,logistic回归分析影响MDS患者PTR的因素。结果:入组63例MDS患者中,34例(53.97%)输注有效,29例(46.03%)输注无效。有效组与无效组在血小板抗体阳性、发热、脾肿大、P-选择素、人抗凝血酶3抗体水平比较上差异均有统计学意义(P<0.05),在性别、年龄、体重指数(BMI)、病程、WHO分型、国际预后评分(IPSS-R)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)比较,差异均无统计学意义(P>0.05)。单因素logistic分析结果显示,上述有统计学差异的指标均为影响MDS患者PTR的相关因素(P<0.05)。多因素logistic回归分析结果显示,血小板抗体阳性、P-选择素、人抗凝血酶3抗体升高均为影响MDS患者PTR的危险因素(OR=1.855、1.927、1.984,P<0.05)。结论:MDS患者反复输注血小板的输血效果不甚理想,PTR主要与血小板抗体阳性、P-选择素和人抗凝血酶3抗体水平有关。

乳腺癌受体阳转阴的发生机理与治疗进展

乳腺癌因其高度异质性,给乳腺癌精准治疗带来挑战。雌激素受体(estrogen receptor, ER)、孕激素受体(progesterone receptor, PR)和人表皮生长因子受体-2(human epidermal growth factor receptor-2, HER2)状态是乳腺癌精准诊疗的重要依据。对于复发或转移性乳腺癌患者,既往治疗主要基于原发病灶受体状态。但研究发现部分患者复发/转移灶受体表达与原发病灶不同,推测可能与肿瘤异质性和治疗后的克隆选择效应相关。相较于受体表达“阴转阳”,受体“阳转阴”的发生率更高,且受体表达的缺失可能导致对原有疗法耐药且预后不良。重新评估乳腺癌复发/转移灶受体状态对调整治疗策略和判断预后具有显著临床意义,但能否基于受体变化情况指导临床决策,在临床研究或实践层面仍存在较大争议。随着靶向药物、免疫疗法及抗体偶联药物(antibody-drug conjugates, ADC)等新型抗肿瘤药物的应用,如何优化受体“阳转阴”乳腺癌患者的治疗方案以提高疗效成为未解决的临床需求。该文旨在深入探讨乳腺癌受体“阳转阴”的机理、预后影响以及治疗现状,为这类患者的治疗提供理论支持和实践指导。

大理州乙肝疫苗接种和乙肝病毒流行现状分析

背景乙型肝炎病毒(hepatitis B virus,HBV)感染是一种公共卫生威胁,世界卫生组织提出了2030年全球消除病毒性肝炎的目标。云南省于2016—2020年开展了乙肝表面抗原(HBV surface antigen,HBsAg)和乙肝表面抗体(HBV surface antibody,HBsAb)监测工作,大理州作为调查现场参与其中。目的了解大理州HBV感染和HBsAb阳性率的关联因素。方法本研究为横断面调查研究,采用分层整群抽样,于2016—2020年对大理州6个年龄组的18904人开展问卷调查和血清采集,应用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测血清HBsAg、HBsAb和乙肝核心抗体(HBVcoreantibody,HBcAb)。运用广义线性混合模型(generalizedlinearmixedmodel,GLMM)分析HBV感染率和HBsAb阳性率的关联因素。结果大理州标化HBV感染率为33.88%,乙肝疫苗接种率为24.42%,及时接种率为16.37%,全程接种率为23.90%,标化HBsAg、HBsAb和HBcAb阳性率分别为2.32%、39.95%和18.57%。GLMM分析显示,男性感染风险低于女性,OR值为0.889(95%CI:0.811~0.974)。相比0~1岁组,≥60岁年龄组感染率更高(且为所有年龄组中最高),OR值为9.223(95%CI:5.440~15.636)。及时接种人群和全程接种人群感染率低于未及时接种人群和未全程接种人群,OR值分别为0.670(95%CI:0.514~0.875)和0.072(95%CI:0.055~0.094)。男性HBsAb阳性率高于女性,OR值为0.922(95%CI:0.862~0.987)。相比0~1岁组,12~18岁年龄组HBsAb阳性率更低(且为所有年龄组中最低),OR值为0.032(95%CI:0.026~0.040)。全程接种人群HBsAb阳性率高于未全程接种人群,OR值为1.161(95%CI:1.391~1.872)。结论大理州HBsAg阳性率低于流行水平,但青少年和成人HBsAb阳性率较低,应做好基础免疫和查漏补种,提高全人群免疫水平。

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中毒性表皮坏死松解症的疗效及安全性

目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)治疗中毒性表皮坏死松解症(TEN)患者的临床疗效及安全性。方法回顾性选取2020年1月至2022年1月海南医学院第一附属医院TEN患者20例,均给予rhTNFR:Fc治疗。治疗21 d后,记录TEN患者临床疗效,比较治疗前与治疗后不同时段(治疗后7、14、21 d)的药疹面积和严重程度指数(DASI)评分[DASI评分平均值,50%DASI(DASI50)、75%DASI(DASI75)、90%DASI(DASI90)所占比例]、血清肿瘤坏死因子α(TNF-α)水平、体温下降时间、皮疹控制时间、住院时间及药物治疗的安全性。结果治疗21 d后,TEN患者中,显效18例(90.00%),有效2例(10.00%)。TEN患者治疗后7、14、21 d的DASI评分分别为(30.44±5.68)、(5.28±2.31)、(2.04±1.12)分,均明显低于治疗前[(52.34±7.45)分],差异均有统计学意义(P<0.05)。相较治疗前、治疗7 d、治疗14 d,治疗21 d后的DASI50(100.00%)、DASI75(100.00%)、DASI90(90.00%)的改善比率最高,差异均有统计学意义(P<0.05)。TEN患者治疗后7、14、21 d的血清TNF-α水平分别为(22.73±5.58)、(15.99±4.60)、(4.44±1.10)pg/mL,均低于治疗前[(33.63±17.36)pg/mL],差异均有统计学意义(P<0.05)。TEN患者体温下降时间为(2.49±0.81)d,皮疹控制时间为(5.19±1.90)d,住院时间为(11.92±4.20)d。治疗期间患者未出现终止治疗或失访,均未出现急性不良反应,随访期间病情未见复发,定期复查结果显示并无合并症、活动性肝炎与结核疾病等。结论rhTNFR:Fc作为治疗TEN疾病的药物其疗效随治疗时间延长而提高,可降低血清TNF-α水平与DASI评分,且安全性较高。

禽呼肠孤病毒在我国部分地区蛋鸡群中的血清流行率和风险因素分析

禽呼肠孤病毒(ARV)在我国流行范围较广,感染家禽后使其出现病毒性关节炎、生长不良和产蛋量下降等表现,对我国养禽业造成较严重的经济损失。为了解我国蛋鸡群中ARV的流行情况及存在的感染风险因素,本试验在2022年11月—2023年3月从北京、天津、河北、山东、河南、江苏、陕西、湖北和重庆9个省市的45个蛋鸡养殖场(其中包括祖代蛋鸡群、父母代蛋鸡群和商品代蛋鸡群),收集共计45份调查问卷和968份血清样本。采用酶联免疫吸附试验(ELISA)检测血清中的ARV抗体,并结合调查问卷,采用单因素分析和逻辑回归分析方法找到蛋鸡出现ARV感染症状的风险因素。ELISA检测结果显示,968份血清样本中检出阳性863份,阳性率为89.15%(95%CI:87.0%~91.0%);单因素分析结果显示,全进全出饲养模式下的蛋鸡出现ARV感染症状的概率显著低于区域性全进全出饲养模式或不同日龄、不同批次混养饲养模式下的蛋鸡,且具有较强程度的关联(P<0.05,0.1<OR<0.3);生物安全防控严格的大、中型规模化养殖场(5万只以上)的蛋鸡出现ARV感染症状的概率显著低于生物安全防控存在不足的小型养殖场(2万~5万只)的蛋鸡,且具有较强程度的关联(P<0.05,0.1<OR<0.3);员工不注意对鸡舍消毒的养殖场饲养的蛋鸡出现ARV感染症状的概率显著高于员工对鸡舍具有较强或一般消毒意识的养殖场饲养的蛋鸡,具有中等程度的关联(P<0.05,1.5<OR<3.0)。综上所述,饲养模式、养殖场规模和员工对鸡舍的消毒意识可能是产蛋鸡群感染ARV的风险因素。

骨保护素/核因子κB受体活化因子/核因子κB受体活化因子配体调节骨代谢及其靶向治疗在口腔领域的应用

背景:骨保护素/核因子κB受体活化因子/核因子κB受体活化因子配体是偶联破骨细胞、成骨细胞分化和活化的重要细胞因子,是调节骨代谢的关键因子,影响着免疫系统、骨的再生和重塑,与牙槽骨的生理性及病理性改建密切相关。目的:分析总结骨保护素/核因子κB受体活化因子/核因子κB受体活化因子配体信号通路对牙槽骨改建的影响及其靶向治疗在口腔领域应用研究中的进展。方法:检索中国知网及PubMed数据库收录的相关文献。中文检索词为“骨保护素,抗RANKL抗体,核因子κB受体活化因子配体,牙周炎,正畸牙移动,种植,牙齿萌出,根尖周病变,牙槽骨吸收”,英文检索词为“OPG,anti-RANKL antibody,RANKL,periodontitis,orthodontic tooth movement,implant,tooth eruption,periapical lesion,alveolar bone resorption”,最终纳入63篇文献进行归纳总结。结果与结论:①抗核因子κB受体活化因子配体通过靶向抑制破骨细胞形成和牙槽骨吸收来治疗口腔疾病;②局部和全身抗核因子κB受体活化因子配体治疗可以抑制牙周炎、种植体周围炎、根尖周病变的进展,且其在预防正畸后复发、增强正畸支抗和种植体骨结合方面也发挥重要作用;③核因子κB受体活化因子配体通过靶向促进破骨细胞分化来治疗口腔疾病;④核因子κB受体活化因子配体治疗可以加速正畸牙移动、缩短治疗周期、减少正畸并发症的发生;⑤虽然抗核因子κB受体活化因子配体治疗存在局限性,但是可以通过合理应用如应用前排除危险因素,应用期间定期口腔维护、避免创伤性牙槽手术等措施来规避。