RFLPs FOR HUMAN PAI-1 GENE IN CHINESE

Plasminogen activator inhibitor 1 (PAI-1) is considered as the main physiological inhibitor of plasminogen activators in plasma which plays an important regulatory role in the control of the fibrinolytic activity in blood. The human PAI-1 gene is located at q21-22 region of chromosome 7. By using human PAI-1 cDNA (a gift from Dr. D. Ginsburg) as a probe, restriction fragment length polymorphisms (RFLPs) were studied with 8 different endonucleases in 35 unrelated Chinese individuals and the results showed as follows: (1) Taq Ⅰdetected allelic 2.7 kb and 1.8 kb fragments, with the frequencies of 0.96 and 0.04 respectively, 2.7 kb homozygote and 2.7 kb/1.8 kb heterozygote appeared with frequencies of 91% and 9%. (2) Sac Ⅰidentified an invariant 4.8kb band and a two-allele polymorphism with fragments of either 23 kb or 16 kb whose frequencies were 0.96 and 0.04. 23kb homozygote and 23kb/16kb heterozygote appeared with the frequencies of 91% and 9%. (3) HindⅢrevealed a single two-allele polymorphism with bands at either 25 kb or 14 kb, with the frequencies of 0.34 and 0.66, 25 kb homozygote, 25 kb/14 kb heterozygote and 14 kb homozygote appeared with the frequencies of 23%, 46% and 31% respectively. The restriction fragment with a size of 1.6kb for TaqⅠwas first reported in the present paper. No polymorphism was observed for EcoRI, BamHI, BglⅡ, PvuⅡand Pst Ⅰ. The RFLPs for PAI-1 gene may be served as important genetic markers for study of thrombotic and other PAI-1 related disorders.

PAI-1和FV基因多态性与静脉血栓的临床意义

目的 一种新技术检测静脉血栓相关基因纤溶酶原激活物抑制剂-1(PAI-1)和凝血因子V(FV)基因多态性,分析清远地区人群基因频率分布情况,指导静脉血栓临床药物治疗。方法 提取2020年4月至2021年8月在清远市人民医院行静脉血栓基因检测的2 281例患者DNA,应用数字荧光分子杂交法检测PAI-1和FV基因多态性,并进行Sanger测序加以验证,大数据分析清远市人民医院就诊患者基因型分布频率,评估男、女性和心、脑血管疾病、肿瘤患者PAI-1和FV基因是否突变与发生静脉血栓的风险,指导抗血栓药物使用。结果 数字荧光分子杂交与Sanger测序结果完全符合(100%);大数据发现本地区人群PAI-1基因呈多态性分布(19.33%、50.33%、30.34%),而FV基因型突变极少,多为野生纯合型(99.91%);PAI-1和FV基因型频率和等位基因频率在男、女性和心、脑血管疾病、肿瘤患者人群中差异无统计学意义(P均>0.05);PAI-1基因多态性与疾病进程无明显相关性。结论 PAI-1基因检测对静脉血栓药物应用极具临床意义,可实现精准化个体治疗,但PAI-1基因多态性与其他疾病和性别无关。

Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用

目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。

PAI-1 genetic polymorphisms influence septic patients’outcomes by regulating neutrophil activity

Background:Plasminogen activator inhibitor-1(PAI-1)plays an important role in the pathophysiology of sepsis,but the exact mechanism remains debatable.In this study,we investigated the associations among the serum levels of PAI-1,the incidence of 4G/5G promoter PAI-1 gene polymorphisms,immunological indicators,and clinical outcomes in septic patients.Methods:A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study,with 28-day mortality as the primary outcome.The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms(SNPs)were examined.Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1,serum level of PAI-1,and 28-day mortality.Results:The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1(4G/4G and 4G/5G)(Odds ratio[OR]:2.49;95%confidence interval[CI]:1.09,5.68).Furthermore,a high serum level of PAI-1 strongly influenced 28-day mortality(OR 3.36;95%CI 1.51,7.49).The expression and activation of neutrophils(OR 0.96;95%CI 0.93,0.99),as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils(OR:1.00;95%CI:1.00,1.00),were both regulated by the genotype of PAI-1.Conclusions:Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1,which might contribute to mortality by affecting neutrophil activity.Thus,patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?

Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.

Multi-genome evolutionary study of the ABC1 gene family and identification of the pleiotropic effects of OsABC1-13 in rice development

In four rice genomes,85 ABC1-family genes were identified by comparative genomics,evolution,genetics,and physiology.One,OsABC1-13,was shown by knockdown and knockout experiments to affect plant height,grain size,and photosynthetic capability.

Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

Heat-inducible SlWRKY3 confers thermotolerance by activating the SlGRXS1 gene cluster in tomato

High temperature stress is one of the major environmental factors that affect the growth and development of plants. Although WRKY transcription factors play a critical role in stress responses, there are few studies on the regulation of heat stress by WRKY transcription factors,especially in tomato. Here, we identified a group I WRKY transcription factor, SlWRKY3, involved in thermotolerance in tomato. First, SlWRKY3 was induced and upregulated under heat stress. Accordingly, overexpression of SlWRKY3 led to an increase, whereas knock-out of SlWRKY3 resulted in decreased tolerance to heat stress. Overexpression of SlWRKY3 accumulated less reactive oxygen species(ROS), whereas knock-out of SlWRKY3 accumulated more ROS under heat stress. This indicated that SlWRKY3 positively regulates heat stress in tomato. In addition,SlWRKY3 activated the expression of a range of abiotic stress-responsive genes involved in ROS scavenging, such as a SlGRXS1 gene cluster.Further analysis showed that SlWRKY3 can bind to the promoters of the SlGRXS1 gene cluster and activate their expression. Collectively, these results imply that SlWRKY3 is a positive regulator of thermotolerance through direct binding to the promoters of the SlGRXS1 gene cluster and activating their expression and ROS scavenging.

Knockdown of the atypical protein kinase genes GhABC1K2-A05 and GhABC1K12-A07 make cotton more sensitive to salt and PEG stress

Activity of bc1 complex kinase(ABC1K)is an atypical protein kinase(aPK)that plays a crucial role in plant mitochondrial and plastid stress responses,but little is known about the responses of ABC1Ks to stress in cotton(Gossypium spp.).Here,we identified 40 ABC1Ks in upland cotton(Gossypium hirsutum L.)and found that the Gh ABC1Ks were unevenly distributed across 17 chromosomes.The GhABC1K family members included 35 paralogous gene pairs and were expanded by segmental duplication.The GhABC1K promoter sequences contained diverse cis-acting regulatory elements relevant to hormone or stress responses.The qRT-PCR results revealed that most Gh ABC1Ks were upregulated by exposure to different stresses.Gh ABC1K2-A05 and Gh ABC1K12-A07 expression levels were upregulated by at least three stress treatments.These genes were further functionally characterized by virus-induced gene silencing(VIGS).Compared with the controls,the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced cotton lines exhibited higher malondialdehyde(MDA)contents,lower catalase(CAT),peroxidase(POD)and superoxide dismutase(SOD)activities and reduced chlorophyll and soluble sugar contents under NaCl and PEG stress.In addition,the expression levels of six stress marker genes(Gh DREB2A,Gh SOS1,Gh CIPK6,Gh SOS2,Gh WRKY33,and Gh RD29A)were significantly downregulated after stress in the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced lines.The results indicate that knockdown of Gh ABC1K2-A05 and Gh ABC1K12-A07 make cotton more sensitive to salt and PEG stress.These findings can provide valuable information for intensive studies of Gh ABC1Ks in the responses and resistance of cotton to abiotic stresses.

Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.

Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene:Hypotheses and conundrums

Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.

AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.

Studies on the temporal,structural,and interacting features of the clubroot resistance gene Rcr1 using CRISPR/Cas9-based systems

Clubroot disease is a severe threat to Brassica crops globally,particularly in western Canada.Genetic resistance,achieved through pyramiding clubroot resistance(CR)genes with different modes of action,is the most important strategy for managing the disease.However,studies on the CR gene functions are quite limited.In this study,we have conducted investigations into the temporal,structural,and interacting features of a newly cloned CR gene,Rcr1,using CRISPR/Cas9 technology.For temporal functionality,we developed a novel CRISPR/Cas9-based binary vector,pHHIGR-Hsp18.2,to deliver Rcr1 into a susceptible canola line(DH12075)and observed that early expression of Rcr1 is critical for conferring resistance.For structural functionality,several independent mutations in specific domains of Rcr1 resulted in loss-offunction,highlighting their importance for CR phenotype.In the study of the interacting features of Rcr1,a cysteine protease gene and its homologous allele in canola were successfully disrupted via CRISPR/Cas9 as an interacting component with Rcr1 protein,resulting in the conversion from clubroot resistant to susceptible in plants carrying intact Rcr1.These results indicated an indispensable role of these two cysteine proteases in Rcr1-mediated resistance response.This study,the first of its kind,provides valuable insights into the functionality of Rcr1.Further,the new vector p HHIGR-Hsp18.2 demonstrated an inducible feature on the removal of add-on traits,which should be useful for functional genomics and other similar research in brassica crops.

Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose metabolism.Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(p.Leu552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this disease.Given the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study.Whole exome sequencing was performed on the patients as well as their family members.The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis.In addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments.Finally,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored.RESULTS A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions.The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster.In addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different species.Moreover,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels,indicating their pathogenic nature.Therefore,based on the patient’s clinical and family history,combined with the results from bioinformatics analysis and functional experiment,the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were classified as pathogenic mutations.Importantly,all these mutations were located within the phosphotyrosinebinding domain of APPL1,which plays a critical role in the insulin sensitization effect.CONCLUSION This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

PAI-1基因4G/5G多态性与行羟氯喹联合肝素治疗的不明原因复发性流产妊娠结局的相关性

目的探究纤溶酶原激活物抑制物-1(PAI-1)基因4G/5G多态性与行羟氯喹联合肝素治疗不明原因复发性流产(URSA)患者妊娠结局的相关性。方法选取2019年1月至2021年1月肇庆市第一人民医院收治的138例URSA患者为研究对象,检测所有受试者PAI-1基因4G/5G位点基因多态性。患者均采用羟氯喹联合肝素治疗,根据妊娠结局分为良好妊娠结局组和不良妊娠结局组。观察两组间PAI-1基因4G/5G基因位点基因型及等位基因的分布差异,并分析PAI-1基因4G/5G位点基因多态性与行羟氯喹联合肝素治疗URSA患者妊娠结局的相关性。结果138例患者中117例患者在治疗后妊娠成功,妊娠成功率为84.78%(117/138)。117例妊娠成功的患者中6例失访,失访率为5.13%(6/117)。111例患者中流产22例,低体质量儿6例,死胎、新生儿死亡各2例,不良妊娠结局发生率为28.83%(32/111)。两组职业类别、工作性质、PAI-1基因型分布比较差异有统计学意义(P<0.05或P<0.01),不良妊娠结局组大专及以上的比例低于良好妊娠结局组[37.50%(12/32)比60.76%(48/79)](P<0.05),生化妊娠史占比高于良好妊娠结局组[81.25%(26/32)比50.63%(40/79)](P<0.01)。不良妊娠结局组PAI-1基因4G等位基因频率高于良好妊娠结局组[65.63%(42/64)比37.97%(60/158)](P<0.01)。多因素Logistic回归分析结果显示,PAI-1基因型4G/4G、4G等位基因及生化妊娠史是行羟氯喹联合肝素治疗URSA患者不良妊娠结局发生的危险因素(OR=3.747,95%CI 1.470~6.024;OR=4.204,95%CI 1.672~6.736;OR=2.672,95%CI 1.269~4.076)(P<0.01)。结论PAI-1基因型4G/4G和4G等位基因与行羟氯喹联合肝素治疗URSA患者发生不良妊娠结局关系密切,是导致行羟氯喹联合肝素治疗URSA患者不良妊娠结局发生的危险因素。

恶性肿瘤合并静脉血栓栓塞症患者PAI-1 4G/5G基因多态性及药物预防

目的探讨肿瘤患者纤溶酶原激活剂抑制物-1(PAI-1)4G/5G基因多态性与静脉血栓栓塞症(VTE)的关系,为临床尽早识别VTE高风险人群并预防VTE提供参考。方法①基因差异性比较:通过医院信息系统查阅病历,对纳入的恶性肿瘤患者,根据是否发生VTE分为静脉血栓组30例和非静脉血栓对照组118例。两组患者均行PAI-14G/5G基因筛查,并对两组进行基因分布频率差异性比较及Hardy-Weinberg遗传平衡检验。②基因干预研究:将纳入的非VTE的肿瘤患者,采用单盲、随机数字表法分为基因指导组30例和非基因指导组30例,基因指导组根据基因检测结果采取VTE预防措施,非基因指导组无基因筛查未采取VTE预防措施,比较两组静脉血栓栓塞事件发生数与发生率。结果静脉血栓组与非静脉血栓对照组的基因分布频率差异有统计学意义(P<0.05),且均符合Hardy-Weinberg遗传平衡;基因指导组发生静脉血栓栓塞事件数0例,非基因指导组静脉血栓栓塞事件数4例(13.33%),差异有统计学意义(P<0.05)。结论PAI-1基因4G/5G多态性可作为肿瘤患者发生VTE的风险判别因子,同时,能为临床尽早识别出VTE高风险人群并采取干预措施提供一定的指导。

STXBP1基因相关脑病患儿的临床表型和基因变异分析

目的探讨STXBP 1基因相关脑病患儿的临床表型和基因变异情况。方法回顾性总结2015年10月至2022年5月收治的11例STXBP 1基因相关脑病患儿的临床资料,分析其临床表型、基因结果、治疗及疗效情况。结果11例患儿中男4例,女7例,10例患儿存在癫痫发作伴发育迟缓,1例患儿仅表现为发育迟缓。癫痫首发年龄为3天~1岁半,3个月以内起病者6例,3~12个月起病者3例,1岁以上起病者1例。常见的发作类型为痉挛和局灶发作。11例患儿均存在脑电图异常包括背景慢、多灶放电、爆发抑制和高度失律等。2例早期为大田原综合征,后期演变为婴儿痉挛症,5例为婴儿痉挛症,余为不能分型的癫痫综合征。4例患儿头颅MRI存在非特异性异常,包括髓鞘化发育落后、额颞部蛛网膜下隙增宽。所有患儿均存在STXBP1基因变异,共有11种突变类型,其中错义突变7例、移码突变1例、剪切突变1例、缺失突变2例,7例患儿的突变位点尚未见文献报道,分别为c.1694T>A、c.1115T>G、C.133_135del、C.1543 dupG、6-17号外显子杂合缺失、C.429+1 G>C、C.855 C>G及c.842_843 insGGACGACGGCCTGTGGATAGC ACT。随访中11例患儿均存在不同程度发育迟缓,2例患儿已死亡,4例患儿存在孤独症样表现。10例癫痫患儿均应用左乙拉西坦治疗,1例为单独应用完全缓解,5例患儿部分有效,4例患儿无效。3例患儿癫痫发作完全缓解,余7例为药物难治性癫痫。结论STXBP1脑病患儿发育迟缓相对严重,婴儿痉挛症表型最常见,癫痫治疗效果存在明显异质性,7个未报道突变位点丰富了STXBP1脑病的基因谱。

MCP-1基因对脓毒症急性肾损伤发生的作用研究

目的研究单核细胞趋化蛋白-1(MCP-1)基因对脓毒症急性肾损伤(AKI)发生的作用。方法选取2022年9月-2023年9月新疆维吾尔自治区人民医院重症医学科收治的50例脓毒症AKI患者作为AKI组,纳入同期50例健康受试者作为对照组。分别采集全部受试者清晨空腹静脉血5 mL,采用ELISA法测定AKI患者及健康人群血清中MCP-1的表达情况;通过原代培养肾小管上皮细胞,利用CK14和CK18抗体进行细胞免疫荧光鉴定,过表达和干扰MCP-1基因,利用CCK8细胞增殖检测试剂盒和RT-qPCR检测肾小管上皮细胞增殖情况和肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素6(IL-6)、白细胞介素10(IL-10)、γ-干扰素(IFN-γ)炎性因子表达的变化。结果与对照组相比,AKI组患者外周血中和尿液中的MCP-1表达量显著升高(P均<0.05);通过细胞免疫荧光鉴定,选择上皮细胞标志物CK14和CK18,原代培养24 h,90%以上的细胞表达细胞标志物CK18,约84%的细胞表达CK14;与NC组相比,siRNA组在24、48 h细胞数量增加(P均<0.05);与MCP-1组相比,siRNA组在24、48、72 h的细胞数量增加(P均<0.05);NC组的IL-1β、IL-6、INF-γ因子的表达水平随时间推移逐渐升高,MCP-1组的IL-1β、IL-6、IL-10、INF-γ和TNF-α因子的表达水平随时间推移逐渐升高,siRNA组的IL-1β、IL-6、INF-γ因子表达水平随时间推移无明显升高趋势。结论MCP-1基因在脓毒症急性肾损伤的发病机制中可能发挥重要作用,该基因可能通过调节IL-1β等炎性细胞因子的表达来抑制肾小管上皮细胞的生长和增殖,从而参与脓毒症患者的AKI过程。

唾液腺腺泡细胞癌中NR4A3基因重排及NOR-1蛋白表达分析

目的:探讨NR4A3基因重排和NOR-1蛋白表达在唾液腺腺泡细胞癌中的表达及在鉴别诊断中的价值。方法:收集2020年5月—2024年1月于上海交通大学医学院附属第九人民医院口腔病理科诊断的唾液腺癌119例,包括腺泡细胞癌(acinic cell carcinoma,AciCC)63例,黏液表皮样癌(mucoepidermoid carcinoma,MEC)31例,分泌性癌(secretory carcinoma,SC)25例。分别使用荧光原位杂交和免疫组织化学染色检测NR4A3基因重排和NOR-1蛋白表达情况,采用SPSS 18.0软件包对数据进行统计学分析。结果:AciCC主要发生于大唾液腺。与MEC和SC相比,AciCC好发于女性(P=0.006)。NR4A3基因重排在AciCC、MEC和SC中的阳性率分别为76.2%(48/63)、0%(0/10)和0%(0/7),NOR-1蛋白表达在AciCC、MEC和SC中的阳性率分别为92.1%(58/63)、9.7%(3/31)和0%(0/25),差异具有统计学意义(P<0.001)。单独使用NR4A3基因重排诊断AciCC时,灵敏度和特异度分别为76.2%和100%。单独使用NOR-1蛋白表达诊断AciCC时,灵敏度和特异度分别为92.1%和94.6%。联合使用NR4A3基因重排和NOR-1蛋白表达诊断AciCC时,灵敏度和特异度分别为96.8%和94.6%,曲线下面积为0.896,诊断价值最优。结论:AciCC好发于女性,主要发病部位为大唾液腺。NR4A3基因重排仅见于AciCC中,在诊断工作中具有100%的特异性,但敏感性较低。NOR-1蛋白表达检测具有很好的灵敏度和特异度,可作为鉴别AciCC、MEC和SC的初筛和替代方法。联合使用NR4A3基因重排和NOR-1蛋白表达检测具有最优的诊断价值。