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21.
肝内胆管癌(ICC)可切除率低,进展期ICC的治疗有效率不高,预后很差。转化治疗在多种晚期肿瘤中有一定的疗效,是目前晚期肿瘤治疗的研究热点。随着对ICC基因组的深入了解和新的治疗药物的开发及组合,基于系统化疗的联合治疗策略,精准靶向治疗,免疫检查点抑制剂等显示出较好的疗效,使得部分进展期ICC病人能降期转化手术,获得长期生存。  相似文献   
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BackgroundBurnout in teachers has been linked to decreased effectiveness as educators, and suboptimal interactions with students. The purpose of this pilot study was to assess the outcomes of a brief Stress Management and Resiliency Training (SMART) program for public school staff.Materials and methodsThis single-arm, prospective trial involved an investigation of the effects of a brief SMART program on participant stress, anxiety, resilience, gratitude, happiness, life satisfaction, and quality of life (QOL).ResultsSignificant improvements were noted in participant anxiety (P < 0.001), stress (P = 0.003), gratitude (P = 0.001), happiness (P < 0.001), life satisfaction (P < 0.001), and QOL (P < 0.001). Most participants reported that the skills learned positively affected interactions with students (77.2%) and coworkers (72.2%).ConclusionsThe SMART program showed promising effectiveness for improving anxiety, stress, gratitude, happiness, life satisfaction and QOL. Given the prevalence and impact of teacher burnout, larger, controlled trials and broader dissemination of the intervention are warranted.  相似文献   
24.

Objective

This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms.

Methods

This was a post-hoc analysis of a multicenter prospective cohort study (SOS-KANTO 2012), which registered OHCA patients in the Kanto region of Japan from January 2012 to March 2013. We included consecutive adult OHCA patients who received epinephrine. The primary result included 1-month favorable neurological outcomes defined as cerebral performance category (CPC) 1 or 2. Secondary results included 1-month survival and return of spontaneous circulation (ROSC) after arrival at the hospital. Multivariable logistic regression analysis determined the association between delay per minute of the time from call to first EA in both pre- or in-hospital settings and outcomes.

Results

Of the 16,452 patients, 9344 were eligible for our analyses. In univariable analysis, the delay in EA was associated with decreased favorable neurological outcomes only when the initial rhythm was a non-shockable rhythm. In multivariable analyses, delay in EA was associated with decreased ROSC (adjusted odds ratio [OR] for one minute delay, 0.97; 95% confidence interval [CI], 0.96–0.98) and 1-month survival (adjusted OR, 0.95; 95% CI, 0.92–0.97) when the initial rhythm was a non-shockable rhythm, whereas during a shockable rhythm, delay in EA was not associated with decreased ROSC and 1-month survival.

Conclusions

While assessing the effectiveness of epinephrine for OHCA, we should consider the time-limited effects of epinephrine. Additionally, consideration of early EA based on the pathophysiology is needed.  相似文献   
25.
26.

Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.

Methods

Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.

Results

Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.

Conclusion

We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment.  相似文献   
27.
Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.  相似文献   

28.
In order to solve the problem of long-term (>9 months) efficacy in the treatment of Alzheimer''s disease (AD) by conventional therapy (CT), a staged and multiply-targeted sequential therapy based on the evolvement of patterns (STEP) was developed. Its main innovations include: (1) the time order of evolution of patterns defined by Chinese medicine (CM) in AD was found, that is, "the orderly pattern evolution starting from Shen (Kidney) deficiency, progressing to phlegm, stasis and fire, and worsening to severe toxin as well as functional collapse"; (2) the cascade hypothesis of Shen deficiency in AD and its sequential therapy based on Shen-reinforcing was proposed, that is, "reinforcing Shen in the early stage and throughout the whole process, resolving phlegm, activating blood and purging fire in the middle stage, detoxifying and replenishing vitality to stop the collapse in the advanced stage", and through meta-analysis, clinical drug use was optimized, thus the leap from "inferential selection" to "evidence-based selection" was realized; (3) the STEP regimen combined with CT maintained cognitive and behavioral stability in AD patients for at least 12 months, with cognitive enhancement and behavioral synergy after 9 months, and cognitive benefit was superior to CT at 9, 12, 15, 18, 21, and 24 months, respectively. The 2-year cognitive improvement rate was increased by 25.64% (P=0.020) and the cognitive deterioration rate was decreased by 48.71% (P=0.000). Among them, the cognitive and functional benefits of Shen-reinforcing therapy for very early AD (350 cases) for 1 year were better than the placebo (P<0.001), and the dementia conversion rate was reduced by 8.85% (P=0.002). The behavioral symptomatic relief of patients with vascular dementia received fire-purging therapy (540 cases) was superior to those received CT (P=0.016). These data suggested that the STEP regimen has synergistic effects on CTs at least in terms of cognitive benefit, and the earlier the use, the greater the benefit will have. Therefore, the STEP regimen should be considered as one of the clinical options, particularly for the dearth of effective pharmaceutical or immunological interventions that are currently available for AD.  相似文献   
29.
Objective: The objective of this study was to gain greater insight into individuals’ quality of life (QOL) definitions, appraisals, and adaptations following spinal cord injury (SCI).

Design: A mixed-methods design, applying the Schwartz and Sprangers response shift (RS) model. RS is a cognitive process wherein, in response to a change in health status, individuals change internal standards, values, or conceptualization of QOL

Setting: Community-dwelling participants who receive medical treatment at a major Midwestern medical system and nearby Veterans’ Affairs hospital.

Participants: A purposive sample of participants with SCI (N?=?40) completed semi-structured interviews and accompanying quantitative measures.

Interventions: Not applicable.

Outcome Measures: Qualitative data were analyzed using content analysis to identify themes. Analysis of variance were performed to detect differences based on themes and QOL, well-being, and demographic and injury characteristics.

Results: Four RS themes were identified, capturing the range of participant perceptions of QOL. The themes ranged from complete RS, indicating active engagement in maintaining QOL, to awareness and comparisons redefining QOL, to a relative lack of RS. Average QOL ratings differed as a function of response shift themes. PROMIS Global Health, Anxiety, and Depression also differed as a function of RS themes.

Conclusion: The RS model contextualizes differences in QOL definitions, appraisals, and adaptations in a way standardized QOL measures alone do not.  相似文献   

30.
全国名中医天津中医药大学第一附属医院针灸科武连仲教授用多年的临床经验总结概括出针刺的理、法、方、穴、术,其创立的"通经止痛"针刺疗法在临床中疗效佳,武老在治疗坐骨神经痛时,取足太阳膀胱经和足少阳胆经具有走窜针感的经穴为主穴,其配伍精确,组方严密,手法独特,可供临床参考。本文将武老运用"痛经止痛"针刺法治疗坐骨神经痛的经验从"理、法、方、穴、术"方面做浅述。  相似文献   
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