Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study ({"type":"clinical-trial","attrs":{"text":"NCT03159195","term_id":"NCT03159195"}}NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.     

生化汤加味促进剖宫产后子宫复旧随机对照试验的系统评价及Meta分析＊

目的 对生化汤加味促进剖宫产后子宫复旧的有效性与安全性进行系统评价，为其在临床应用提供循证医学证据。方法 检索中国生物医学文献数据库（CBM）、中国知网（CNKI）、万方资源数据库（WanFang）、维普期刊数据库（VIP）、Cochrane Library、PubMed、Web of Science等，检索时限为建库至2020年7月，选择生化汤加味促进剖宫产后子宫复旧的随机对照试验（RCT），采用Cochrane系统评价员手册提供的偏倚风险评估工具进行文献质量评价，应用RevMan5.3软件进行Meta分析。结果 共纳入12篇RCT文献，共计1804例剖宫产产妇；Meta分析结果显示，生化汤加味联合缩宫素组在产后第1、3、5天子宫底高度［MD = -0.75，95%CI（-1.35， -0.15），P < 0.00001；MD = -1.92，95%CI（-3.13， -0.72），P < 0.00001；MD = -1.92，95%CI（-3.79， -0.06），P < 0.00001］低于单用缩宫素组，联合用药组血性恶露时间［MD = -1.52，95%CI（-2.71，-0.34），P < 0.00001］和产后恶露持续时间［MD = -4.47，95%CI（-6.20，-2.75），P < 0.00001］均短于单用缩宫素组。结论 生化汤加味联合缩宫素与单用缩宫素比较，更能促进产后子宫复旧；不良反应少，报道的仅有4例出现轻微腹泻，安全性较高；但由于纳入文献质量较低，上述结论尚需更多的随机对照临床研究加以证实。     

肺鳞癌治疗新靶点FGFR的研究进展

肺癌是目前全球发病率和死亡率均居前列的恶性肿瘤，其中肺鳞癌经手术、放化疗等综合治疗后，其疗效仍不满意。随着分子靶向治疗在肺腺癌中取得了令人瞩目的成果，而肺鳞癌患者中EGFR基因突变及ALK融合基因少见，急需探索新的靶点指导肺鳞癌患者的临床治疗。研究表明，FGFR家族（FGFR1-4）是肺鳞癌中突变频率较高的基因，FGFR基因的激活突变和扩增与肺鳞癌的发生和发展密切相关，同时许多小分子 FGFR 抑制剂在临床应用中已经取得较好的治疗效果。目前，许多FGFR抑制剂治疗肺鳞癌的临床试验也正在进行研究，针对FGFR靶点的基因治疗可为肺鳞癌的治疗提供一种新的策略。本文就FGFR在肺鳞癌的靶向治疗中的最新研究进展进行综述。     

Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro

Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.     

同型半胱氨酸对高血压患者脑卒中复发风险的影响

目的探讨高血压合并脑卒中患者的血浆同型半胱氨酸（Hcy）水平与其他危险因素对于脑卒中复发的影响。 方法分析徐州市中心医院心内科和徐州医科大学附属医院神经外科自2012年5月至2013年12月收治的1623例高血压脑卒中患者的基线资料，中位随访4.9年，根据随访事件中是否发生脑卒中分为复发组（312例）与未复发组（1311例）。Kaplan-Meier生存分析比较不同危险因素脑卒中复发率的差异，单因素与多因素Cox回归模型分析影响脑卒中复发的独立危险因素，以及危险因素之间的交互作用。 结果复发组年龄、空腹血糖、Lg Hcy的水平，以及糖尿病、房颤的患病率均高于未复发组（P<0.05）。Kaplan-Meier生存分析显示，糖尿病、房颤、年龄≥60岁、空腹血糖≥7.0 mmol/L、Hcy≥15 μmol/L的脑卒中复发率明显升高（Log-rank检验，P<0.05）。多因素Cox回归模型分析显示，高龄、Lg Hcy水平升高，以及房颤、糖尿病是脑卒中复发的独立危险因素。Lg Hcy分别与糖尿病、空腹血糖、年龄存在交互作用。 结论血浆Hcy水平升高既是高血压合并脑卒中患者卒中复发的独立危险因素，又通过与糖尿病、高龄、空腹血糖水平升高的交互作用显著增加脑卒中复发风险。     

Challenges facing HIV-positive persons who use drugs and their families in Vietnam

It is hypothesized that persons who use drugs (PWUD) in Vietnam who are also HIV-positive may face additional challenges in psychosocial outcomes, and these challenges may extend to their family members. In this study, we examined depressive symptoms, stigma, social support, and caregiver burden of HIV-positive PWUD and their family members, compared to the outcomes of HIV-negative PWUD and their family members. Baseline, 3-month, and 6-month assessment data were gathered from 83 PWUD and 83 family members recruited from four communes in Phú Th? Province, Vietnam. For PWUD, although we observed a general decline in overall stigma over time for both groups, HIV-positive PWUD consistently reported significantly higher overall stigma for all three periods. Depressive symptoms among family members in both groups declined over time; however, family members of HIV-positive PWUD reported higher depressive symptoms across all three periods. In addition, family members of HIV-positive PWUD reported lower levels of tangible support across all three periods. Caregiver burden among family members of HIV-positive PWUD increased significantly over time, whereas the reported burden among family members of HIV-negative PWUD remained relatively unchanged. The findings highlight the need for future interventions for PWUD and family members, with targeted and culturally specific strategies to focus on the importance of addressing additional stigma experienced by PWUD who are HIV-positive. Such challenges may have direct negative impact on their family members' depressive symptoms, tangible support, and caregiver burden.     

2型糖尿病患者不同脂质参数与糖尿病肾病的关系

目的:探讨2型糖尿病(T2DM)患者不同脂质参数与糖尿病肾病(DKD)发生的相关性。方法:检测226例T2DM患者血清TC、TG、LDL-C、HDL-C水平及相关生化指标,计算血浆致动脉硬化指数(AIP)以及脂质三角相关指标(TC/HDL-C、TG/HDL-C、LDL-C/HDL-C)。根据DKD临床诊断标准和Mogensen分期标准分为:Ⅰ~Ⅱ期组136例,Ⅲ期组55例,Ⅳ~Ⅴ期组35例。应用多因素logistic回归分析不同脂质参数与DKD发生的关系。结果:与Ⅰ~Ⅱ期组相比,随着DKD分期加重,TC、TG、LDL-C、LDL-C/HDL-C、AIP水平明显增高(P<0.01)。LDL-C/HDL-C和AIP与24 h尿蛋白水平呈正相关(r=0.724;r=0.769,均P<0.05)。LDL-C/HDL-C和AIP是T2DM合并DKD患者的独立预测因子(P=0.002;P=0.004)。结论:LDL-C/HDL-C和AIP对T2DM合并DKD病情进展有较高的预测价值,可为临床诊治提供参考。