Effectiveness of cardioneuroablation in different subtypes of vasovagal syncope

BACKGROUND Cardioneuroablation(CNA)has shown encouraging results in patients with vasovagal syncope(VVS).However,data on different subtypes was scarce.METHODS This observational study retrospectively enrolled 141 patients[mean age:40±18 years,51 males(36.2%)]with the diagnosis of VVS.The characteristics among different types of VVS and the outcomes after CNA were analyzed.RESULTS After a mean follow-up of 4.3±1.5 years,41 patients(29.1%)experienced syncope/pre-syncope events after CNA.Syncope/pre-syncope recurrence significantly differed in each subtype(P=0.04).The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure(n=6,16.7%),followed by mixed(n=26,30.6%)and vasodepressive(n=9,45.0%).Additionally,a significant difference was observed in the analyses of the Kaplan-Meier survival curve(P=0.02).Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type(P<0.01).Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity(DC)level than those without(7.4±1.0 ms vs.9.0±1.6 ms,P=0.01).Patients with DC<8.4 ms had an 8.1(HR=8.1,95%CI:2.2-30.0,P=0.02)times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC≥8.4 ms,and this association still existed after adjusting for age and sex(HR=8.1,95%CI:2.2-30.1,P=0.02).CONCLUSIONS Different subtypes exhibit different event-free rates.The vasodepressive type exhibited the lowest event-free rate,but those patients with DC≥8.4 ms might benefit from CNA.

Identification of prognostic molecular subtypes and model based on CD8+ T cells for lung adenocarcinoma

Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.

《世界反兴奋剂条例》第2.3条构成要件的法教义学审视

在第2.3条兴奋剂违纪的主观构成要件问题上,通过结合国际体育仲裁院多年来的相关案例与《世界反兴奋剂条例》第2.3条三个版本的释义分析发现,过失可以成为“拒绝样本采集”行为的主观构成要件,所以若是因过失造成“拒绝样本采集”,可以适用《世界反兴奋剂条例》10.5条,即基于非重大过失或疏忽而减轻处罚。而在第2.3条兴奋剂违纪的客观构成要件问题上,除第2.3条明确规定的要件外,检查行为的合法性也是构成2.3条违规的客观构成要件,但是只有重大违法检查行为才可以抗辩,轻微违法行为不构成运动员合理的抗辩理由。在分析2.3条违规构成及当事人主观过错时还应注意区分分析法律认识错误、事实认识错误和反向错误问题,这都应在案件中予以全面考虑。

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020

Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development

BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and suitable subpopu-lations for mRNA vaccination.METHODS Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas.Genes with somatic mutations and copy number variations were identified by cBioPortal analysis.The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis.The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells(APCs).Tumor-associated antigens were overexpressed in tumors and associated with prognosis,genomic alterations,and APC infiltration.A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes.The weighted gene coexpression network analysis(WGCNA)was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines.immune subtypes showed distinct cellular and clinical characteristics.The IS1 and IS3 immune subtypes were immunologically“cold”.The IS2 and IS4 immune subtypes were immunologically“hot”,and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes.IS1-related modules were identified with the WGCNA algorithm.Ultimately,five hub genes(RBP4,KNG1,METTL7A,F12,and ABAT)were identified,and they might be potential biomarkers for mRNA vaccines.CONCLUSION AURKA,CCNB1,CDC25C,CDK1,TRIP13,PES1,MCM3,PPM1G,NEK2,KIF2C,PTTG1,KPNA2,and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development.The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination.RBP4,KNG1,METTL7A,F12,and ABAT are potential biomarkers for mRNA vaccines.

Rare synchronous colorectal carcinoma with three pathological subtypes: A case report and review of the literature

BACKGROUND Synchronous colorectal carcinomas(SCRC)are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient.Their incidence is low and the number of pathological types of SCRC is usually no more than two.It is very unusual that the pathological findings of a patient with SCRC show more than two different pathological subtypes.Here,we report a rare case of SCRC with three pathological subtypes.CASE SUMMARY A 75-year-old woman who had no previous medical history or family history was admitted to the hospital because of intermittent hematochezia for more than a month.Colonoscopy displayed an irregularly shaped neoplasm of the rectum,a tumor-like lesion causing intestinal stenosis in the descending colon,and a polypoidal neoplasm in the ileocecum.Subsequently,she underwent total colectomy,abdominoperineal resection for rectal cancer,and ileostomy.After operation,the pathological report showed three pathological subtypes including well-differentiated adenocarcinoma of the ascending colon,moderately differen-tiated adenocarcinoma of the descending colon,and mucinous adenocarcinoma of the rectum.She is now recovering well and continues to be closely monitored during follow-up.CONCLUSION Preoperative colonoscopy examination,imaging examination,and extensive intraoperative exploration play important roles in reducing the number of missed lesions.

Blood typing and transfusion therapy in a patient with A2 subtype acute myeloid leukemia M2:A case report

BACKGROUND Acute myeloid leukemia(AML)is one of the most common types of leukemia in adults.However,AML is relatively rare in the population overall,accounting for only about 1 percent of all cancers.Treatment for AML can be very effective for some patients,yet it leaves others with serious and even life-threatening side effects.Chemotherapy is still the primary treatment for most AML,but over time,leukemia cells become resistant to chemotherapy drugs.In addition,stem cell transplantation,targeted therapy,and immunotherapy are currently available.At the same time,with the progression of the disease,the patient may have corresponding complications,such as coagulation dysfunction,anemia,granulocytopenia,and repeated infection,so transfusion supportive therapy will be involved in the overall treatment regime.To date,few articles have reported on blood transfusion treatment options for patients with ABO subtypes AML-M2.Blood transfusion therapy is an important supportive treatment for AML-M2,and accurate determination of patients'blood type is one of the most important steps in the treatment process.In this study,we explored blood typing and supportive treatment strategies for a patient with A2 subtype AML-M2 to provide the basis for treatment for all patients.CASE SUMMARY In order to determine the blood type of the patient,serological and molecular biological methods were used for reference tests,and the genetic background was studied to determine the patient's final blood type and select the appropriate blood products for infusion treatment.According to the results obtained by serological and molecular biological methods,the blood type of the patient was A2 subtype;the genotype was A02/001;the irregular antibody screening was negative,and anti-A1 was found in the plasma.According to the overall treatment plan,active anti-infection,elevated cells,component blood transfusion support,and other rescue and supportive treatments were given,and the patient successfully passed the stage of myelosuppression after chemotherapy.Re-examination of bone marrow smears showed that AL was in complete remission of bone marrow signs,and minimal residual leukemia lesions suggested no cells with obvious abnormal immunophenotype(residual leukemia cells<10-4).CONCLUSION The infusion of patients with A2 subtype AML-M2 with A irradiated platelets and O washing red blood cells can meet the needs of clinical treatment.

Classification of patients with metastatic colorectal cancer into consensus molecular subtypes into real-world: A pilot study

BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targeted therapy regimens.However,due to the inherent heterogeneity of this condition,identifying reliable predictive biomarkers for targeted therapies remains challenging.A recent promising classification system—the consensus molecular subtype(CMS)system—offers the potential to categorize mCRC patients based on their unique biological and molecular characteristics.Four distinct CMS categories have been defined:immune(CMS1),canonical(CMS2),metabolic(CMS3),and mesenchymal(CMS4).Nevertheless,there is currently no standardized protocol for accurately classifying patients into CMS categories.To address this challenge,reverse transcription polymerase chain reaction(RT-qPCR)and next-generation genomic sequencing(NGS)techniques may hold promise for precisely classifying mCRC patients into their CMSs.AIM To investigate if mCRC patients can be classified into CMS categories using a standardized molecular biology workflow.METHODS This observational study was conducted at the University of Chile Clinical Hospital and included patients with unresectable mCRC who were undergoing systemic treatment with chemotherapy and/or targeted therapy.Molecular biology techniques were employed to analyse primary tumour samples from these patients.RT-qPCR was utilized to assess the expression of genes associated with fibrosis(TGF-βandβ-catenin)and cell growth pathways(c-MYC).NGS using a 25-gene panel(TumorSec)was performed to identify specific genomic mutations.The patients were then classified into one of the four CMS categories according to the clinical consensus of a Tumour Board.Informed consent was obtained from all the patients prior to their participation in this study.All techniques were conducted at University of Chile.RESULTS Twenty-six patients were studied with the techniques and then evaluated by the Tumour Board to determine the specific CMS.Among them,23%(n=6),19%(n=5),31%(n=8),and 19%(n=5)were classified as CMS1,CMS2,CMS3,and CMS4,respectively.Additionally,8%of patients(n=2)could not be classified into any of the four CMS categories.The median overall survival of the total sample was 28 mo,and for CMS1,CMS2,CMS3 and CMS4 it was 11,20,30 and 45 mo respectively,with no statistically significant differences between groups.CONCLUSION A molecular biology workflow and clinical consensus analysis can be used to accurately classify mCRC patients.This classification process,which divides patients into the four CMS categories,holds significant potential for improving research strategies and targeted therapies tailored to the specific characteristics of mCRC.

三阴型乳腺癌基于组织学、免疫组化分型的分析

目的探讨基于组织学、免疫组化的三阴型乳腺癌(triple-negative breast cancer,TNBC)分型标准,为完善TNBC分型治疗提供理论依据。方法根据组织学特点和免疫组化标志物AR、CD8、FOXC1的表达对TNBC进行分型,比较TNBC亚型的临床病理特征、预后差异。结果93例TNBC中腔面雄激素受体型23例(24.7%),免疫调节型24例(25.8%),基底样免疫抑制型39例(42.0%),间充质型7例(7.5%)。TNBC亚型的临床病理特征:pT分期(P=0.030)、组织学分级(P<0.001)、肿瘤间质淋巴细胞浸润模式(P<0.001)、PD-L1(P<0.001)、HER2低表达(P=0.024)差异均有统计学意义;各亚型间的无瘤生存率差异无统计学意义(P>0.05)。单因素分层生存分析:亚型间pT1分期的无瘤生存率差异有统计学意义(P=0.011),其余临床病理特征均为非独立预后因素。结论TNBC基于组织学、免疫组化分型的临床病理特征有差异,有望替代复杂基因表达谱分型,为TNBC分型和靶向治疗提供理论依据。

脂肪肉瘤的超声图像特征分析

目的 分析并总结脂肪肉瘤的超声图像特征。方法 回顾性分析我院经手术病理证实的31例脂肪肉瘤患者的超声资料,分析不同病理亚型的脂肪肉瘤超声图像特征。结果 31例患者中,去分化脂肪肉瘤13例,高分化脂肪肉瘤10例,多形性脂肪肉瘤4例,黏液样脂肪肉瘤4例;肿瘤最大径为(16.97±9.70)cm,以等或高回声(61.3%,19/31)为主,且回声分布多不均匀(90.3%,28/31),CDFI多表现为乏血供,Adler血流分级以0、Ⅰ级为主(96.8%,30/31)。其中,高分化脂肪肉瘤以高回声为主(70.0%,7/10);去分化脂肪肉瘤边界多不清晰(92.3%,12/13),以低回声(46.2%,6/13)和高回声(30.8%,4/13)的双相模式为主;多形性脂肪肉瘤边界多清晰(3/4);黏液样脂肪肉瘤CDFI均表现为极度乏血供(4/4)。结论 脂肪肉瘤的超声表现具有一定的特征性,对临床辅助诊断该病能够提供一定的帮助。

ABO血型变异的分子基础研究

目的 对临床ABO血型变异标本进行ABO亚型、类孟买血型与基因型关联性研究,以探讨这2种血型产生的可能分子背景,为ABO血型的准确鉴定与预判提供精确的基因检测靶点和理论依据。方法 对2022年2—12月瑞金医院2.42万名血型鉴定患者,以及期间来自外院送检10例ABO疑难标本(疑似ABO亚型3例,疑似类孟买血型7例)进行血清学分析,对血清学鉴定为ABO亚型、类孟买血型的行DNA直接测序或克隆后测序分析ABO、FUT1、FUT2基因序列。结果 在共计2.42万血型鉴定患者中检出7例ABO亚型;外院送检的10例疑难标本检出2例ABO亚型、1例正常A型、7例类孟买血型。我们共鉴定出:1)9例ABO亚型,表型及其对应基因型分别为:1例A_(el)(AEL.02/O.01.02)、1例A_(el)B(AEL.05/B.01)、3例B_(3)(2例B3.03/O.01.01、1例B3.03/O.01.02)、1例B(A)(BA.02/O.01.01)、1例AB_(weak)(A1.02/BW.07)、1例B_(weak)(BW.31/O.01.02)、1例A_(2)B_(weak)(A2.05/BW.31);2)7例类孟买血型,表型及其对应基因型分别为:1例AB_(m)^(h)(FUT1^(*)01N.13/FUT1^(*)01N.13)、4例A_(m)^(h)(3例FUT1^(*)01N.06/FUT1^(*)01N.13、1例FUT1^(*)01N.13/FUT1^(*)01N.13)、2例B_(m)^(h)(FUT1^(*)01N.06/FUT1^(*)01N.06、FUT1^(*)01N.06/FUT1^(*)01N.13),7例类孟买的FUT2基因型均为FUT2^(*)01/FUT2^(*)01。结论 ABO血型变异标本需联合血清学与分子生物学方法进行鉴定,方能提高对血型变异标本的鉴定准确率,从而为临床安全输血、器官移植、胎母免疫性溶血病的预测与防治提供参考。

B亚型新等位基因803delC的分子生物学研究

目的分析研究1例新的B亚型等位基因血清学特点和分子生物学机制。方法应用血清学方法检测患者ABO血型。应用序列特异性引物-聚合酶链反应(PCR-SSP)检测ABO血型基因。应用Sanger基因序列分析检测ABO基因1~7外显子编码区域,确定基因突变位点。结果血清学鉴定患者正定型为O型,反定型为B型。PCR-SSP基因分型结果为A/O型,存在A基因,与血清学结果不符。进一步Sanger双链测序结果显示该标本在ABO^(*)B.01/ABO^(*)O.01.01的基础上,第7外显子803位置缺失C碱基。该突变最终导致多肽链上发生p.Ala268Gly和p.Phe269Ser的氨基酸替换,并且从269位置开始产生新的开放阅读框,新的开放阅读框第20号氨基酸为终止密码子,导致B基因表达终止。进一步ABO基因克隆测序证明该突变点位于ABO*B.01基因上,该突变已提交NCBI数据库,收录编号为OR343908。结论在中国人群中发现1种新的导致B变异型的ABO等位基因,基因检测方法可辅助鉴定血清学正、反定型不符的疑难血型。

Ax22亚型导致家族性血型鉴定错误的研究

目的通过对ABO血型为Ax22/B型的患者及其家属因A亚型造成血清学血型鉴定错误的案例进行分析,总结ABO血型鉴定过程中的注意事项及A亚型的输血策略。方法分别选取A、B两种不同厂家的微柱凝胶血型鉴定卡及试管法在常温和4℃孵育10 min两种条件下对患者及其子女进行血清学血型鉴定;对所有标本进行吸收放散试验及血型基因鉴定;分别用微柱凝胶法和聚凝胺法对同一组标本进行交叉配血。结果B试剂卡凝集强度明显高于A试剂卡,且正定型B试剂卡可以在常温下检测到A抗原,A试剂卡仅在4℃孵育10 min后才可检测到A抗原。试管法血型可明确显示A亚型的反应格局。吸收放散试验显示所有标本红细胞表面均存在A抗原,经基因测序患者为Ax22/B.01,其子女基因型为Ax22/O.01.01。微柱凝胶法交叉配血相合,聚凝胺法镜下可见细胞凝集,交叉配血不合。结论Ax22会造成检测结果假阴性,如正反定型不一致或者对检测结果有任何疑问,应选用试管法或其他检测系统进行复核,必要时进行基因检测;Ax22亚型在配血时有假阴性的可能,有较高的输血风险。

磁共振弛豫时间定量成像预测乳腺浸润性导管癌分子亚型的价值

目的探讨磁共振弛豫时间定量成像对乳腺浸润性导管癌(IDC)分子亚型的预测价值。方法对79例IDC患者行MRI常规扫描及弛豫时间定量成像,根据病灶免疫组化结果分为不同的免疫组化指标组、分子亚型组,比较各组病灶MRI征象、T_(1)值、T_(2)值差异,并采用受检者工作特征(ROC)曲线评价单独使用T_(1)、T_(2)值及二者联用对IDC分子亚型的鉴别诊断价值。结果79例患者共82个病灶中,Luminal A型16个(19.51%)、Luminal B1型11个(13.41%)、Luminal B2型27个(32.93%)、酪氨酸激酶受体-2过度表达型(Erb-B2过表达型)14个(17.07%)、三阴型(TNBC)14个(17.07%)。各分子亚型患者年龄、病灶分布、最大径、形态、边缘、强化表现差异均无统计学意义(P>0.05)。免疫组化指标中仅Ki-67阳性组T_(1)值高于阴性组(P<0.05)。ROC曲线分析显示,Ki-67阳性病灶T_(1)值临界值为2145 ms,约登指数为0.368,敏感度为53.47%,特异度为83.33%,曲线下面积(AUC)为0.640(95%CI:0.527~0.744)。Luminal A、Luminal B1、Luminal B2、Erb-B2过表达型、TNBC分子亚型间T_(1)、T_(2)值差异均无统计学意义(P>0.05),而Luminal型病灶T_(1)、T_(2)值均低于TNBC型(P<0.05)。ROC曲线分析显示,联合T_(1)、T_(2)值鉴别Luminal型/TNBC型的效能优于单独使用T_(1)、T_(2)值。结论T_(1)mapping可作为预测IDC肿瘤Ki-67高低表达程度的方法之一,联合使用T_(1)、T_(2)值可提高预测Luminal型/TNBC型的效能。

H9N2 AIV灭活疫苗免疫SPF鸡攻毒后肺组织免疫相关基因表达变化研究

[目的]本试验旨在探究H9N2亚型禽流感病毒攻击对H9灭活疫苗免疫SPF鸡呼吸系统的影响。[方法]选用36只3周龄SPF鸡,随机分为对照组(Con)、攻毒组(Flu)、免疫后攻毒组(Vac+Flu)。以每只0.4 mL剂量免疫接种H9灭活疫苗,3周后以10~6 EID_(50)的病毒量进行攻毒,采集拭子、血清、气管、肺组织等样品,通过血凝抑制(HI)试验、RT-PCR、荧光定量PCR(qPCR)等方法检测血清中HI抗体滴度、肺脏流感病毒M基因拷贝数以及免疫相关基因CD4、CD8、GATA3、T-bet、IL-4、IL-13、TNF-α、IFN-γ、Perforin、Granzyme、FasL、Fas等的表达量;并利用HE染色、免疫组织化学的方法观察气管、肺脏的病理变化及病毒特异性抗原NP蛋白的分布特征。[结果]HI试验结果显示,SPF鸡疫苗免疫后可产生较高的H9N2 AIV抗体效价。免疫保护试验和RT-PCR结果显示,SPF鸡疫苗免疫后攻毒仍能检测到机体排毒和流感病毒M基因在肺脏组织中的表达。HE染色和免疫组化结果显示,接种H9N2 AIV灭活疫苗后能够明显减轻SPF鸡气管和肺脏的病理损伤,降低气管、肺脏中的病毒载量。荧光定量PCR结果显示,接种H9N2 AIV灭活疫苗后能够提高SPF鸡肺脏中Th1、Th2细胞因子分泌水平,促进穿孔素/颗粒酶途径相关基因表达进而增强肺脏中细胞毒性反应。[结论]H9N2疫苗免疫鸡感染H9病毒后虽然仍存在排毒现象,但其抗病毒免疫系统活跃、其主要器官病毒载量降低,建议按照流感疫苗免疫程序进行免疫接种,提高对流感的防控水平。

基于影像组学和自动机器学习的PA患者肾上腺静脉取血结果的研究

目的建立基于高分辨率增强CT影像和自动机器学习技术的原发性醛固酮增多症(Primary Aldosteronism,PA)亚型术前预测模型。方法回顾性研究经肾上腺静脉取血(Adrenal Venous Sampling,AVS)结果亚型诊断的PA患者312例,其中,207例诊断为单侧优势(AVS-右∶AVS-左=93∶114),105例诊断为双侧优势。纳入患者初诊CT影像,基于薄层静脉期图像提取双侧肾上腺影像组学特征,并定义影像组学商值特征为双侧肾上腺对应影像组学特征的比值,再将特征向量输入自动机器学习进行模型训练。结果根据自动模型筛选,随机森林分类器在预测AVS结果方面取得了较好的整体性能,其中准确度为0.7500,召回率为0.7466,受试者工作特征曲线下面积为0.8792。结论本系统在预测PA患者的AVS结果方面展示出了一定的潜力,因此,机器学习模型可以在常规临床实践中辅助预测PA的亚型诊断。

MRI特征辅助分类乳腺癌分子亚型的临床研究

目的 应用磁共振(MRI)图像中提取的特征和机器学习方法来帮助区分乳腺癌分子亚型,以期为临床诊治提供参考。方法 回顾性分析我院于2021年10月-2023年10月间确诊的178例乳腺癌患者的临床资料,每个患者肿瘤的形状、MRI特征和基于直方图的特征是使用内部软件从增强前和三次增强后的MRI图像上提取的。同时收集临床和病理资料。基于机器学习模型识别重要的成像特征并建立预测IDC亚型的模型。采用留一法交叉验证(LOOCV)避免模型过度拟合,采用Kruskal-Wallis检验确定统计学意义。结果 LOOCV过程生成一个具有不同特征的模型,在排名前20位的特征中,有11项在IDC亚型之间存在显著差异(P<0.05)。综合前九种病理和影像特征,预测模型对IDC亚型的识别准确率为83,4%。病理和影像联合模型对各亚型的准确率分别为89.2%(ERPR1)、63.6%(ERPR-/HER21)和8 2.5%(TN)。当仅结合前9个成像特征时,预测模型在LOOCV上识别IDC亚型的总体准确率为71.2%。病理和影像联合模型对各亚型的准确率分别为69.9%(ERPR1)、62.9%(ERPR-/HER21)和81.0%(TN)。结论 我们开发了一个基于机器学习的预测模型,该模型使用从M RI提取的特征来区分具有显著预测能力的IDC亚型。

广西H9N2亚型禽流感病毒疫苗候选株的筛选

【目的】筛选出免疫原性更优的H9N2亚型禽流感病毒(AIV)疫苗候选株用于新型疫苗研发,为加强对H9N2亚型AIV的防控提供技术支持。【方法】以2000—2020年广西地区分离获得的36株H9N2亚型AIV分离株为试验材料,依据HA基因遗传进化分析选择12株不同年份、不同地域及不同宿主来源的H9N2亚型AIV代表株,与目前使用的商品化H9亚型AIV疫苗株(SS株)进行交叉血凝抑制试验(HI)及抗原性分析,根据抗原分析结果选择其中具有不同抗原差异的代表株制备油乳剂灭活疫苗,并分别与商品化H9亚型AIV疫苗(SS株)进行交叉免疫保护试验。【结果】在36株H9N2亚型AIV广西分离株中有31株属于Y280-Like(9.4.1),其中26株属于分支I、5株属于分支II,另外5株属于G1-Like(h9.4.1),与我国常用疫苗株分属于不同进化分支。12株H9N2亚型AIV广西代表性分离株灭活后的HA效价≥7 log2,病毒灭活效果良好,可用于制备油乳剂灭活疫苗,且制备的油乳剂灭活疫苗稳定性和安全性良好。根据交互HI抗体滴度计算出各毒株间的抗原相关值(R),结果发现A/chicken/Guangxi/C227/2015(H9N2)株(简称C227株)与其他毒株的抗原性无明显差异,对应的R在0.72~0.93间波动;疫苗交叉保护试验结果也表明,C227株制备的油乳剂灭活疫苗对不同毒株的免疫保护率均高于80%,且免疫保护效果优于A/chicken/Guangxi/CX/2013(H9N2)株(简称CX13株),说明C227株更适合作为H9N2亚型AIV灭活疫苗的候选株。【结论】基于抗原性分析和免疫原性测定筛选出的A/chicken/Guangxi/C227/2015(H9N2)株对广西地区绝大部分H9N2亚型AIV流行株的免疫保护效果良好,可作为疫苗候选株用于研制新型H9N2亚型AIV疫苗。

卵巢微乳头亚型浆液性交界性肿瘤临床病理与分子特征分析

目的探讨卵巢微乳头亚型浆液性交界性肿瘤(micropapillary serous borderline tumor,MSBT)的临床病理学特征、免疫表型、分子改变、鉴别诊断、治疗和预后。方法收集14例卵巢MSBT的临床资料,采用免疫组化EnVision法染色分析IMP3的表达,运用qRT-PCR法和Sanger测序法检测BRAF和KRAS的基因突变,分析其临床病理特征并复习相关文献。结果患者年龄27~56岁,平均41.7岁;9例为双侧卵巢肿物;11例术前血清CA125值升高。肿瘤切面呈囊实性,伴囊内乳头状物。14例卵巢MSBT均呈乳头状结构,特征性的细长微乳头直接从囊壁或大的无分支乳头上发散出来,乳头长宽比>5,乳头被覆细胞呈立方至多角形,轻-中度异型性,微乳头区范围均>5 mm。5例伴微浸润;6例伴腹膜非浸润性种植;5例伴腹水均可见异型肿瘤细胞;3例伴淋巴结受累;9例伴砂粒体。免疫表型:ER、PR、CA125、CK7和WT-1均呈阳性,p53野生型,HER2、IMP3均阴性,Ki67增殖指数为5%~30%。分子病理学特征:14例中KRAS基因突变3例(3/14,21.4%),突变位点分别为G12C、G12D和Q70(无义突变);BRAF V600E均未突变;BRAF T559I突变1例(1/14,7.1%)。7例患者行根治性手术,另7例患者行保守性手术,术后均未经特殊治疗。随访时间1~12年,14例患者中5例有复发。结论MSBT形态学特殊,多双侧发病,易伴腹膜种植,易复发,诊断时应与经典型卵巢浆液性交界性肿瘤鉴别。

活动性肺结核患者血清ATG3和FOXO3水平变化对患者病情进展及预后评估的相关性分析

目的分析活动性肺结核患者血清中自噬相关基因3(ATG3)和叉头转录因子O亚型3(FOXO3)表达水平变化以及与患者病情进展及预后的关系。方法以2019年9月~2022年9月于本院就诊的91例活动性肺结核患者(观察组)为研究对象,另选取同时期于本院体检的91例健康体检者作为对照组;酶联免疫吸附法检测血清中ATG3和FOXO3表达水平;利用Spearman相关分析活动性肺结核患者血清中ATG3和FOXO3表达水平与患者病情严重程度之间的相关性;采用Logistic回归分析影响活动性肺结核患者预后的因素;采用ROC曲线分析血清中ATG3和FOXO3表达水平对活动性肺结核患者预后评估的价值。结果与对照组相比,观察组血清中ATG3和FOXO3表达水平显著下降(P<0.05);与轻症组相比,重症组患者血清中ATG3和FOXO3表达水平显著下降(P<0.05);与预后不良组相比,预后良好组患者血清中ATG3和FOXO3表达水平显著升高(P<0.05);预后良好组与预后不良组患者ESR、PCT、CRP、TNF-α、INF-γ和IL-2相比差异具有统计学意义(P<0.05);Spearman相关分析显示活动性肺结核患者血清中ATG3和FOXO3表达水平与患者病情严重程度呈负相关(P<0.05);Logistic回归分析结果显示,ESR、CRP、ATG3和FOXO3为影响活动性肺结核患者预后不良的因素(P<0.05);ROC曲线分析显示,血清中ATG3和FOXO3表达水平联合预测活动性肺结核患者预后较ATG3和FOXO3单一指标预测效果更优(P<0.05)。结论活动性肺结核患者血清中ATG3和FOXO3表达水平显著下降,且与活动性肺结核病情严重程度相关,二者联合对活动性肺结核患者预后具有较高的评估价值。