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New treatment for osteoarthritis: Gene therapy. 骨关节炎的新疗法:基因疗法。
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1093/pcmedi/pbad014
Xinyu Li, Leyao Shen, Zhenghan Deng, Zeyu Huang

Osteoarthritis is a complex degenerative disease that affects the entire joint tissue. Currently, non-surgical treatments for osteoarthritis focus on relieving pain. While end-stage osteoarthritis can be treated with arthroplasty, the health and financial costs associated with surgery have forced the search for alternative non-surgical treatments to delay the progression of osteoarthritis and promote cartilage repair. Unlike traditional treatment, the gene therapy approach allows for long-lasting expression of therapeutic proteins at specific sites. In this review, we summarize the history of gene therapy in osteoarthritis, outlining the common expression vectors (non-viral, viral), the genes delivered (transcription factors, growth factors, inflammation-associated cytokines, non-coding RNAs) and the mode of gene delivery (direct delivery, indirect delivery). We highlight the application and development prospects of the gene editing technology CRISPR/Cas9 in osteoarthritis. Finally, we identify the current problems and possible solutions in the clinical translation of gene therapy for osteoarthritis.

骨关节炎是一种复杂的退行性疾病,影响整个关节组织。目前,骨关节炎的非手术治疗主要是缓解疼痛。虽然终末期骨关节炎可以通过关节置换术治疗,但与手术相关的健康和经济成本迫使人们寻找其他非手术治疗方法来延缓骨关节炎的进展并促进软骨修复。与传统治疗方法不同,基因治疗方法允许治疗蛋白在特定部位持久表达。在这篇综述中,我们总结了骨关节炎基因治疗的历史,概述了常见的表达载体(非病毒,病毒),基因传递(转录因子,生长因子,炎症相关细胞因子,非编码rna)和基因传递模式(直接传递,间接传递)。重点介绍CRISPR/Cas9基因编辑技术在骨关节炎中的应用及发展前景。最后,我们确定目前的问题和可能的解决方案,在骨关节炎基因治疗的临床翻译。
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引用次数: 0
Overexpressed miR-539 exacerbates Pseudomonas aeruginosa puenmonia by promoting inflammatory responses. 过表达的miR-539通过促进炎症反应加重铜绿假单胞菌肺炎。
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1093/pcmedi/pbad012
Jianbo Li, Qi Yang, Xinghong Gao, Feng Chen, Xinxia Gu, Xikun Zhou, Lei Chen, Jie Liu, Min Wu
Pseudomonas aeruginosa is an opportunistic Gr am-negativ e bac-terium that causes a series of life-threatening acute and/or c hr onic infections in humans, often in persons with immunode-ficiency . P . aeruginosa has been listed as one of the priority bacteria that r equir es extensiv e r esearc h and ur gent de v elopment of new antibiotic treatments by the World Health Organization ( WHO ) in 2017. 1 In r ecent years, numer ous studies have shown that miRNAs play an important role in infection and inflammatory responses. 2 , 3 Our earlier r esearc hes suggest that miRNAs are a k e y regulator of
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引用次数: 0
Investigating association between gut microbiota and sarcopenia-related traits: a Mendelian randomization study. 调查肠道微生物群与肌肉减少症相关特征之间的关系:一项孟德尔随机研究。
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1093/pcmedi/pbad010
Jiaxi Zhao, Rui Liang, Quhong Song, Shiyu Song, Jirong Yue, Chenkai Wu

Background: Observational studies have indicated a potential link between gut microbiota and sarcopenia. However, the underlying mechanisms and a causal relationship have not been established. Thus, the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits, including low hand-grip strength and appendicular lean mass (ALM), to shed light on the gut-muscle axis.

Methods: To investigate the potential impact of gut microbiota on low hand-grip strength and ALM, we utilized a two-sample Mendelian randomization (MR) approach. Summary statistics were obtained from genome-wide association studies of gut microbiota, low hand-grip strength, and ALM. The primary MR analysis employed the random-effects inverse-variance weighted (IVW) method. To assess the robustness, we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier (MR-PRESSO) test to detect and correct for horizontal pleiotropy, as well as the MR-Egger intercept test and leave-one-out analysis.

Results: Alcaligenaceae, Family XIII, and Paraprevotella were positively associated with the risk of low hand-grip strength (P-values < 0.05). Streptococcaceae were negatively associated with low hand-grip strength (P-values < 0.05). Eight bacterial taxa (Actinomycetales, Actinomycetaceae, Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, Bacteroides, Marvinbryantia, and Phascolarctobacterium) were associated with a higher risk of ALM (P-values < 0.05). Eubacterium fissicatena group was negatively associated with ALM (P-values < 0.05).

Conclusion: We found several gut microbiota components causally associated with sarcopenia-related traits. Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota, contributing to a better understanding of the gut-muscle axis.

背景:观察性研究表明肠道微生物群与肌肉减少症之间存在潜在联系。然而,潜在的机制和因果关系尚未建立。因此,本研究的目的是研究肠道微生物群与肌肉减少症相关特征(包括低握力和阑尾瘦质量(ALM))之间可能的因果关系,以阐明肠道肌肉轴。方法:为了研究肠道微生物群对低握力和ALM的潜在影响,我们采用了双样本孟德尔随机化(MR)方法。从肠道微生物群、低握力和ALM的全基因组关联研究中获得了汇总统计数据。主要MR分析采用随机效应反方差加权(IVW)方法。为了评估稳健性,我们使用MR多效性残差和异常值(MR- presso)检验进行敏感性分析,以检测和校正水平多效性,以及MR- egger截距检验和留一分析。结果:Alcaligenaceae、Family XIII和Paraprevotella与低握力风险呈正相关(链球菌科与低握力风险负相关)(放线菌科、放线菌科、拟杆菌科、卟啉单胞菌科、Prevotellaceae、拟杆菌科、Marvinbryantia和Phascolarctobacterium的p值)与较高的ALM风险相关(裂裂atena真杆菌组与ALM负相关(p值)我们发现几种肠道菌群成分与肌肉减少症相关的特征有因果关系。我们的研究结果为通过调节肠道微生物群来预防和治疗肌肉减少症的新策略提供了见解,有助于更好地理解肠道肌肉轴。
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引用次数: 0
Partial treatment response to alectinib in metastatic non-small cell lung cancer with KIDINS220-ALK fusion. 转移性非小细胞肺癌合并KIDINS220-ALK融合对alectinib的部分治疗反应。
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1093/pcmedi/pbad011
Yanna Lei, Shasha Zeng, Xiaoyu Li, Pei Shu, Weiya Wang, Yongsheng Wang
1 Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China 2 Clinical Trial Center , NMP A Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu 610041, China 3 State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China 4 Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China ∗Correspondence: Yongsheng Wang, wangys@scu.edu.cn §Yanna Lei and Shasha Zeng contributed equally to this work.
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引用次数: 0
Impact of age and tumor size on the development of the Kasabach-Merritt phenomenon in patients with kaposiform hemangioendothelioma: a retrospective cohort study. 年龄和肿瘤大小对卡泊样血管内皮瘤患者发生Kasabach-Merritt现象的影响:一项回顾性队列研究
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1093/pcmedi/pbad008
Jiangyuan Zhou, Yuru Lan, Tong Qiu, Xue Gong, Zixin Zhang, Chunshui He, Qiang Peng, Fan Hu, Xuepeng Zhang, Guoyan Lu, Liqing Qiu, Feiteng Kong, Yongbo Zhang, Siyuan Chen, Yi Ji

Introduction: The Kasabach-Merritt phenomenon (KMP) is a severe complication of kaposiform hemangioendothelioma (KHE). The risk factors for KMP need further investigation.

Methods: The medical records of patients with KHE were reviewed. Univariate and multivariate logistic regression models were used for the risk factors for KMP, and the area under the receiver operator characteristic (ROC) curve was used to assess the predictive power of risk factors.

Results: A total of 338 patients with KHE were enrolled. The incidence of KMP was 45.9%. Age of onset (P < 0.001, odds ratio [OR] 0.939; 95% confidence interval [CI] 0.914-0.966), lesion size (P < 0.001, OR 1.944; 95% CI 1.646-2.296), mixed type (P = 0.030, OR 2.428; 95% CI 1.092-5.397), deep type (P = 0.010, OR 4.006; 95% CI 1.389-11.556), and mediastinal or retroperitoneal lesion location (P = 0.019, OR 11.864; 95% CI 1.497-94.003) were correlated with KMP occurrence through multivariate logistic regression. ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset (P < 0.001, OR 7.206, 95% CI 4.073-12.749) and a lesion diameter of 5.35 cm (P < 0.001, OR 11.817, 95% CI 7.084-19.714). Bounded by a lesion size of 5.35 cm, we found significant differences in tumor morphology, age of onset, treatments, and hematological parameters. Using an onset age of 4.75 months as a cutoff, we found significant differences in tumor morphology, lesion size, hematological parameters, and prognosis.

Conclusion: For KHE patients with an onset age <4.75 months and/or lesion diameter >5.35 cm, clinicians should be wary of the occurrence of KMP. Active management is recommended to improve the prognosis.

Kasabach-Merritt现象(KMP)是kaposiform血管内皮瘤(KHE)的严重并发症。KMP的危险因素需要进一步调查。方法:回顾KHE患者的病历资料。对KMP的危险因素采用单因素和多因素logistic回归模型,并采用受试者操作特征曲线下面积(receiver operator characteristic, ROC)评价危险因素的预测能力。结果:共纳入338例KHE患者。KMP的发生率为45.9%。发病年龄(P P P = 0.030, OR 2.428;95% CI 1.092-5.397),深度型(P = 0.010, OR 4.006;95% CI 1.389-11.556),纵隔或腹膜后病变位置(P = 0.019, or 11.864;通过多因素logistic回归,95% CI 1.497-94.003)与KMP发生相关。ROC曲线分析显示,发病年龄的最佳临界值为4.75个月(P P)。结论:对于发病年龄为5.35 cm的KHE患者,临床医生应警惕KMP的发生。建议积极治疗以改善预后。
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引用次数: 2
Genetic factors for differentiated thyroid cancer in French Polynesia: new candidate loci. 法属波利尼西亚分化型甲状腺癌的遗传因素:新的候选基因座。
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1093/pcmedi/pbad015
Monia Zidane, Marc Haber, Thérèse Truong, Frédérique Rachédi, Catherine Ory, Sylvie Chevillard, Hélène Blanché, Robert Olaso, Anne Boland, Éric Conte, Mojgan Karimi, Yan Ren, Constance Xhaard, Vincent Souchard, Jacques Gardon, Marc Taquet, André Bouville, Jean-François Deleuze, Vladimir Drozdovitch, Florent de Vathaire, Jean-Baptiste Cazier

Background: Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations.

Methods: We analyzed more than 300 000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population.

Results: We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66 × 10-7, 2.39 × 10-7, and 7.19 × 10-7 and corresponding odds ratios of 2.02, 1.89, and 2.37.

Conclusion: Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated.

背景:1966年至1974年,法国在法属波利尼西亚(FP)进行了大气检测,在那里,分化型甲状腺癌(DTC)的发病率很高。然而,到目前为止,还没有对该人群的DTC遗传因素进行足够大的研究来得出明确的结论。本研究旨在分析本地FP人群中DTC风险的遗传因素。方法:我们分析了283例DTC病例和418例FP匹配对照的30多万个单核苷酸多态性(snp)基因分型,其中大多数在第一次核试验时年龄小于15岁。我们分析了队列的遗传谱,以确定种群亚群。然后我们完成了对整个人群的全基因组分析研究。结果:我们在FP群体中发现了一个特定的遗传结构,反映了亚洲和欧洲人群的混合。我们在6q24.3、10p12.2和17q21.32确定了三个与DTC风险增加相关的区域。这些位点的先导snp的p值分别为1.66 × 10-7、2.39 × 10-7和7.19 × 10-7,比值比分别为2.02、1.89和2.37。结论:我们的研究结果提示基因座6q24.3、10p12.2和17q21.32在DTC风险中起作用。然而,与为白种人设计的微阵列芯片进行基因分型相比,全基因组测序方法更适合表征这些因素。此外,这三个新基因座的功能影响还需要进一步探索和验证。
{"title":"Genetic factors for differentiated thyroid cancer in French Polynesia: new candidate loci.","authors":"Monia Zidane,&nbsp;Marc Haber,&nbsp;Thérèse Truong,&nbsp;Frédérique Rachédi,&nbsp;Catherine Ory,&nbsp;Sylvie Chevillard,&nbsp;Hélène Blanché,&nbsp;Robert Olaso,&nbsp;Anne Boland,&nbsp;Éric Conte,&nbsp;Mojgan Karimi,&nbsp;Yan Ren,&nbsp;Constance Xhaard,&nbsp;Vincent Souchard,&nbsp;Jacques Gardon,&nbsp;Marc Taquet,&nbsp;André Bouville,&nbsp;Jean-François Deleuze,&nbsp;Vladimir Drozdovitch,&nbsp;Florent de Vathaire,&nbsp;Jean-Baptiste Cazier","doi":"10.1093/pcmedi/pbad015","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad015","url":null,"abstract":"<p><strong>Background: </strong>Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations.</p><p><strong>Methods: </strong>We analyzed more than 300 000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population.</p><p><strong>Results: </strong>We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66 × 10<sup>-7</sup>, 2.39 × 10<sup>-7,</sup> and 7.19 × 10<sup>-7</sup> and corresponding odds ratios of 2.02, 1.89, and 2.37.</p><p><strong>Conclusion: </strong>Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9735912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pig-to-Human xenotransplantation: Moving toward organ customization. 猪到人的异种移植:向器官定制迈进。
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1093/pcmedi/pbad013
Mengyu Gao, Jie Zhang, Rui Wang, Guang Yang, Ji Bao
a
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引用次数: 1
Correction to: New treatment for osteoarthritis: Gene therapy. 修正:骨关节炎的新疗法:基因疗法。
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1093/pcmedi/pbad016

[This corrects the article DOI: 10.1093/pcmedi/pbad014.].

[更正文章DOI: 10.1093/pcmedi/pbad014.]。
{"title":"Correction to: New treatment for osteoarthritis: Gene therapy.","authors":"","doi":"10.1093/pcmedi/pbad016","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad016","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/pcmedi/pbad014.].</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/ed/pbad016.PMC10294634.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10201091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma. 失调的 miRNA 可调节胰腺导管腺癌中与肿瘤微环境相关的信号网络。
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-03-10 eCollection Date: 2023-03-01 DOI: 10.1093/pcmedi/pbad004
Tiantian Liu, Zhong Chen, Wanqiu Chen, Ryan Evans, Jane Xu, Mark E Reeves, Michael E de Vera, Charles Wang

The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.

胰腺导管腺癌(PDAC)的脱瘤性和复杂的肿瘤微环境为制定有效的治疗策略带来了巨大挑战。针对肿瘤基质的策略虽然潜力巨大,但由于缺乏对肿瘤微环境(TME)内分子动态的了解,其成功率有限。为了更好地了解 miRNA 对 TME 重编程的影响,并探索将循环 miRNA 作为 PDAC 的诊断和预后生物标志物,我们利用 RNA-seq、miRNA-seq 和单细胞 RNA-seq (scRNA-seq),研究了 PDAC TME 中受血浆和肿瘤组织中 miRNA 调节的失调信号通路。我们在PDAC肿瘤组织中的大分子RNA-seq鉴定出了1445个显著差异表达的基因,其中细胞外基质和结构组织是富集程度最高的通路。我们的miRNA-seq在PDAC患者血浆和肿瘤组织中分别发现了322个和49个异常表达的miRNA。我们发现,PDAC 患者血浆中表达异常的 miRNA 靶向了许多 TME 信号通路。结合 PDAC 患者肿瘤的 scRNA-seq,我们的研究结果发现,这些失调的 miRNA 与细胞外基质(ECM)重塑、细胞-ECM 通信、上皮-间质转化以及由 TME 不同细胞组分协调的免疫抑制密切相关。这项研究的发现有助于开发基于 miRNA 的基质靶向生物标记物或治疗 PDAC 患者。
{"title":"Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma.","authors":"Tiantian Liu, Zhong Chen, Wanqiu Chen, Ryan Evans, Jane Xu, Mark E Reeves, Michael E de Vera, Charles Wang","doi":"10.1093/pcmedi/pbad004","DOIUrl":"10.1093/pcmedi/pbad004","url":null,"abstract":"<p><p>The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9595475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Workup of difficult-to-treat asthma: implications from treatable traits. 难治性哮喘的检查:可治疗特征的意义。
IF 5.3 4区 医学 Q1 Medicine Pub Date : 2023-03-01 DOI: 10.1093/pcmedi/pbad003
Qing Zhang, Wen Wen Wu, Lei Li, Vanessa M McDonald, Yu Cheng Chen, Gang Wang, Peter G Gibson

Traditional stepwise approach usually adjusts the treatment regimen based on changes in asthma symptoms and severity to achieve good asthma control. However, due to the generalized heterogeneity and complexity of asthma, its therapeutic efficacy in difficult-to-treat asthma is limited. Recently, a precision medicine approach based on the identification and intervention of treatable traits of chronic airway disease has been proposed and appears to be of greater benefit to asthmatics. We reported a 71-year-old male with uncontrolled asthma and multiple exacerbations over the past year. He complained of persistent dyspnea despite high-dose of inhaled corticosteroids plus other controllers. Does this patient have some potential treatable traits contributing to difficult-to-treat asthma? Through a multidimensional assessment of three domains including pulmonary, extrapulmonary, and behavioral/risk factors, 15 treatable traits were identified in the patient, mainly including airflow limitation, eosinophilic airway inflammation, small airway dysfunction, exacerbation prone, dilated cardiomyopathy, diabetes mellitus, inhaler device polypharmacy, smoking, and the absence of an asthma action plan. After targeted treatment for these treatable traits, the patient experienced significant improvement in dyspnea and he could maintain good asthma control with low-dose inhaled corticosteroids and long-acting β2-agonist. This study shows that, in response to the limitation of a stepwise approach to therapy, treatable traits is a new strategy where patients are individually assessed for a specified set of treatable problems, and an individualized treatment program is developed and implemented based on this multidimensional assessment, especially for difficult-to-treat asthma.

传统的渐进式方法通常根据哮喘症状和严重程度的变化来调整治疗方案,以达到良好的哮喘控制。然而,由于哮喘的普遍异质性和复杂性,其对难治性哮喘的治疗效果有限。最近,一种基于慢性气道疾病可治疗特征的识别和干预的精准医学方法被提出,似乎对哮喘患者有更大的好处。我们报告了一位71岁的男性,在过去的一年里,他患有不受控制的哮喘和多次发作。尽管吸入了大剂量的皮质类固醇和其他控制剂,他仍抱怨持续呼吸困难。这个病人是否有一些潜在的可治疗的特征导致难治性哮喘?通过对肺、肺外和行为/危险因素三个领域的多维度评估,确定了患者的15个可治疗特征,主要包括气流受限、嗜酸性气道炎症、小气道功能障碍、加重倾向、扩张性心肌病、糖尿病、吸入器多药、吸烟和缺乏哮喘行动计划。针对这些可治疗的特征进行靶向治疗后,患者呼吸困难明显改善,低剂量吸入皮质类固醇和长效β2激动剂可维持良好的哮喘控制。这项研究表明,为了应对逐步治疗方法的局限性,可治疗的特征是一种新的策略,在这种策略中,患者被单独评估一组特定的可治疗问题,并根据这种多维评估制定和实施个性化的治疗方案,特别是对于难以治疗的哮喘。
{"title":"Workup of difficult-to-treat asthma: implications from treatable traits.","authors":"Qing Zhang,&nbsp;Wen Wen Wu,&nbsp;Lei Li,&nbsp;Vanessa M McDonald,&nbsp;Yu Cheng Chen,&nbsp;Gang Wang,&nbsp;Peter G Gibson","doi":"10.1093/pcmedi/pbad003","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad003","url":null,"abstract":"<p><p>Traditional stepwise approach usually adjusts the treatment regimen based on changes in asthma symptoms and severity to achieve good asthma control. However, due to the generalized heterogeneity and complexity of asthma, its therapeutic efficacy in difficult-to-treat asthma is limited. Recently, a precision medicine approach based on the identification and intervention of treatable traits of chronic airway disease has been proposed and appears to be of greater benefit to asthmatics. We reported a 71-year-old male with uncontrolled asthma and multiple exacerbations over the past year. He complained of persistent dyspnea despite high-dose of inhaled corticosteroids plus other controllers. Does this patient have some potential treatable traits contributing to difficult-to-treat asthma? Through a multidimensional assessment of three domains including pulmonary, extrapulmonary, and behavioral/risk factors, 15 treatable traits were identified in the patient, mainly including airflow limitation, eosinophilic airway inflammation, small airway dysfunction, exacerbation prone, dilated cardiomyopathy, diabetes mellitus, inhaler device polypharmacy, smoking, and the absence of an asthma action plan. After targeted treatment for these treatable traits, the patient experienced significant improvement in dyspnea and he could maintain good asthma control with low-dose inhaled corticosteroids and long-acting β<sub>2</sub>-agonist. This study shows that, in response to the limitation of a stepwise approach to therapy, treatable traits is a new strategy where patients are individually assessed for a specified set of treatable problems, and an individualized treatment program is developed and implemented based on this multidimensional assessment, especially for difficult-to-treat asthma.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/91/pbad003.PMC10037422.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9274915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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Precision Clinical Medicine
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