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Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.  相似文献   
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孙莉  赵毅 《现代肿瘤医学》2019,(13):2420-2424
三阴性乳腺癌(triple negative breast cancer,TNBC)是雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)及人类表皮生长因子受体(human epidermal growth factor-2,HER-2)均不表达的乳腺癌。按其功能特征可归纳为5类分子分型:以DNA修复缺陷或生长因子为途径的基底细胞样三阴性乳腺癌;以上皮-间充质转化和肿瘤干细胞为特征的间质样三阴性乳腺癌;免疫调节型三阴性乳腺癌;雄激素受体过表达的管腔/分泌型三阴性乳腺癌;HER-2富集型三阴性乳腺癌。三阴性乳腺癌恶性程度高且异型性较大,其治疗困难且预后较差,内分泌治疗及靶向治疗不敏感。目前很多学者对于三阴性乳腺癌的治疗各有研究,并有临床试验证实下述治疗有效。  相似文献   
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MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer‐enriched miRNA is required for prostate tumorigenesis. We identify miR‐205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR‐205 is not required for normal prostate development and homeostasis, genetic deletion of miR‐205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR‐205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR‐205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR‐205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR‐205 in the progression of Pten null‐induced prostate cancer.  相似文献   
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张旖  李占军  张文龙 《中医学报》2020,35(6):1307-1311
目的:探讨疏血通脉汤联合傍针刺治疗中风后肩手综合征(shoulder-hand syndrome after stroke,SHSAS)的临床疗效,并观察其对患者上肢肢体痉挛程度、血液流变学以及上肢活动能力的影响。方法:110例痰瘀阻络型SHSAS患者按照随机数字表法分为对照组与联合组,每组55例。两组患者均给予神经内科常规药物和肢体功能康复训练治疗。对照组联合傍针刺法治疗,联合组在对照组治疗基础上给予疏血通脉汤。两组患者均以4周为1个疗程,治疗1个疗程。记录比较两组患者治疗前后上肢肢体痉挛程度(Ashworth)、上肢活动能力(FMA)、肩手综合征量表(shoulder hand syndrome scale,SHSS)、视觉模拟评分(visual simulation scoring,VAS)、中医证候评分,高切全血黏度、低切全血黏度、血浆黏度和血小板聚集率等血液流变学指标,并比较治疗效果。结果:联合组有效率为96.36%,对照组有效率为83.64%,两组患者有效率比较,差异有统计学意义(P0.05)。治疗后,联合组高切全血黏度、低切全血黏度、血浆黏度与血小板聚集率水平均低于对照组,差异有统计学意义(P0.05);联合组Ashworth评分低于对照组、上肢FMA评分高于对照组,差异有统计学意义(P0.05);联合组SHSS评分和中医证候评分均低于对照组,差异有统计学意义(P0.05);联合组VAS评分低于对照组,差异有统计学意义(P0.05)。结论:疏血通脉汤联合傍针刺治疗SHSAS患者疗效显著,能有效改善患者血液流变学,缓解疼痛程度和上肢痉挛,提高上肢活动能力。  相似文献   
6.

Objectives

To determine: (i) the behaviour change techniques used by a sample of Australian physiotherapists to promote non-treatment physical activity; and (ii) whether those behaviour change techniques are different to the techniques used to encourage adherence to rehabilitation exercises.

Design

Cross-sectional survey.

Method

An online self-report survey was advertised to private practice and outpatient physiotherapists treating patients with musculoskeletal conditions. The use of 50 behaviour change techniques were measured using five-point Likert-type scale questions.

Results

Four-hundred and eighty-six physiotherapists responded to the survey, with 216 surveys fully completed. Most respondents (85.1%) promoted non-treatment physical activity often or all of the time. Respondents frequently used 29 behaviour change techniques to promote non-treatment physical activity or encourage adherence to rehabilitation exercises. A similar number of behaviour change techniques was frequently used to encourage adherence to rehabilitation exercises (n = 28) and promote non-treatment physical activity (n = 26). Half of the behaviour change techniques included in the survey were frequently used for both promoting non-treatment physical activity and encouraging adherence to rehabilitation exercises (n = 25). Graded tasks was the most, and punishment was the least, frequently reported technique used to promote non-treatment physical activity and encourage adherence to rehabilitation exercises.

Conclusions

Respondents reported using similar behaviour change techniques to promote non-treatment physical activity and encourage adherence to rehabilitation exercises. The variability in behaviour change technique use suggests the behaviour the physiotherapist is promoting influences their behaviour change technique choice. Including the frequently-used behaviour change techniques in non-treatment physical activity promotion interventions might improve their efficacy.  相似文献   
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对当前的疾病预防控制体系和机构面临的体系不健全、政府投入不充分、事业发展不平衡、人才缺失和能力不足、缺乏系统的理论指导、体系的碎片化严重、与社会经济发展的战略衔接不力、机构内部内生动力和活力不足以及体系治理能力不足等问题做了讨论分析,以期进一步分析在健康中国战略和事业单位机构改革等宏观环境变化所带来的机遇以及疾控体系的发展策略和具体措施,促进疾病预防控制事业在改革中谋发展。  相似文献   
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