The role of lncRNA MSC-AS1/miR-29b-3p axis-mediated CDK14 modulation in pancreatic cancer proliferation and Gemcitabine-induced apoptosis

Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related death due to the failure of traditional therapies. In the present study, we attempted to construct a lncRNA-miRNA-mRNA network which may modulate PDAC cell proliferation and Gemcitabine-induced cell apoptosis starting from CDK14, a new member of the CDK family and an oncogene in many cancers. Based on TCGA data, a significant positive correlation was observed between lncRNA MSC-AS1 and CDK14. Moreover, MSC-AS1 expression was upregulated in PDAC tissues. Higher MSC-AS1 expression was correlated with poorer prognosis in patients with PDAC. MSC-AS1 knockdown in Panc-1 and BxPC-3 cells significantly inhibited the cell proliferation. Moreover, miR-29b-3p, which has been reported to act as a tumor suppressor, was predicted to bind to both MSC-AS1 and CDK14. Contrary to MSC-AS1, higher miR-29b-3p expression was correlated to better prognosis in patients with PDAC. In both PDAC cell lines, miR-29b-3p negatively regulated MSC-AS1 and CDK14. As confirmed using luciferase reporter gene and RIP assays, MSC-AS1 served as a ceRNA for miR-29b-3p to counteract miR-29b-mediated CDK14 repression. MSC-AS1 knockdown inhibited CDK14 protein levels and PDAC proliferation and enhanced gemcitabine-induced cell death and apoptosis while miR-29b-3p inhibition exerted an opposing effect; the effect of MSC-AS1 knockdown was partially attenuated by miR-29b-3p inhibition. Taken together, we demonstrated that MSC-AS1/miR-29b-3p axis modulates the cell proliferation and GEM-induced cell apoptosis in PDAC cell lines through CDK14. We provided a novel experimental basis for PDAC treatment from the perspective of lncRNA-miRNA-mRNA network.     

带蒂大网膜瓣在乳腺癌术后乳房再造中的应用研究

目的探讨带蒂大网膜瓣在乳腺癌术后乳房再造中的临床应用。方法2013 年 5 月—2017 年 10 月，对 205 例乳腺癌患者行改良根治术联合带蒂大网膜瓣移植再造乳房。患者均为女性；年龄 26～58 岁，平均 34.9 岁。左侧 127 例、右侧 78 例；肿瘤直径 2～5 cm，平均 2.9 cm。乳腺癌分期：Ⅰ期 120 例，Ⅱ期 85 例。病理诊断：浸润性导管癌 126 例，浸润性小叶癌 79 例。病程 10～92 d，平均 38.5 d。肿物切除后遗留缺损范围为 9 cm×6 cm～18 cm×12 cm。带蒂大网膜瓣切取范围为 18 cm×10 cm～22 cm×16 cm。结果根据术中观察的组织特点，将大网膜分为 4 种类型，稀薄型（42 例，20.5%）、中间型（133 例，64.9%）、肥厚型（24 例，11.7%）、缺如型（6 例，2.9%）。术后带蒂大网膜瓣均成活，切口Ⅰ期愈合。患者均获随访，随访时间 6～74 个月，平均 24.5 个月；其中 83 例随访达 5 年以上。再造乳房外形可、弹性好，无挛缩变形。供区仅遗留线性瘢痕，腹部功能无影响。随访期间无乳腺癌复发。结论带蒂大网膜瓣切取安全可靠、质地优良，是乳腺癌术后乳房再造的理想方法之一。     

椎弓回植与椎板切除治疗轻中度峡部裂性腰椎滑脱症疗效比较

目的比较椎弓回植与椎板切除治疗单节段峡部裂性腰椎滑脱症的临床疗效。方法回顾分析 2014 年 3 月—2016 年 7 月采用椎弓回植或椎板切除治疗的 66 例单节段峡部裂性腰椎滑脱症患者临床资料，根据手术方式不同分为试验组（34 例，采用椎弓完整回植固定椎间融合内固定术）和对照组（32 例，采用椎板切除并椎间融合内固定术）。两组患者性别、年龄、病程、病变节段、Meyerding 分度及术前疼痛视觉模拟评分（VAS）、Oswestry 功能障碍指数（ODI）、日本骨科协会（JOA）评分等一般资料比较差异，均无统计学意义（P>0.05），具有可比性。记录并比较两组患者手术时间、术中出血量、并发症情况、术后试验组回植椎弓融合情况及两组硬膜外瘢痕形成情况。术前及术后 3、6、12 个月和末次随访时行腰痛 VAS 评分、JOA 评分及 ODI 评分，并参照侯树勋等提出的标准进行临床疗效评价。 结果所有患者均顺利完成手术，无神经损伤加重、硬脊膜撕裂、感染等并发症发生。试验组手术时间与对照组比较差异无统计学意义（t=0.583，P=0.562），但术中出血量显著低于对照组（t=2.134，P=0.037）。66 例患者均获随访，随访时间 13～18 个月，平均 16.2 个月。所有患者术后临床症状明显改善。对照组 7 例于术后 3 个月发现体位变动时椎管狭窄症状，5 例于术后 18 个月出现轻度双下肢麻木症状；其余患者未发生感染、神经损伤等并发症。试验组 34 例硬膜外瘢痕组织均被完全阻滞于回植椎弓以外，对照组有 11 例硬膜外瘢痕组织侵入椎管内。末次随访时试验组椎间植骨及椎弓回植融合率均为 100%，对照组椎间植骨融合率亦为 100%。两组术后各时间点 VAS 评分、ODI 评分、JOA 评分均较术前显著改善（P<0.01）；试验组术后 3 个月和末次随访时 ODI 评分、JOA 评分显著优于对照组（P<0.05），其余时间点两组间各评分比较差异无统计学意义（P>0.05）。参照侯树勋等提出的标准进行临床疗效评价，试验组优良率为 91.2%，与对照组优良率 84.4%比较差异无统计学意义（χ²=1.092，P=0.573）。 结论与椎板切除相比，椎弓回植能更好地改善术后神经症状，最大程度重建了骨性椎管，恢复了椎管内环境稳定性，对于峡部裂性腰椎滑脱是一种较好的手术方式。     

Diabetes fatalism and its emotional distress subscale are independent predictors of glycemic control among Lebanese patients with type 2 diabetes

Background: Achieving and sustaining optimal glycemic control in type 2 diabetes (T2DM) is difficult because of socio-cultural and psychosocial factors including diabetes fatalism. Diabetes fatalism is ‘a complex psychological cycle characterized by perceptions of despair, hopelessness, and powerlessness’.

Purpose: The purpose of this paper is to explore whether diabetes fatalism and other psychosocial and socio-cultural variables are correlates of glycemic control in Lebanese population with T2DM.

Methods: A convenience sample of 280 adult participants with T2DM were recruited from a major hospital in greater Beirut-Lebanon area and from the community. Diabetes fatalism was assessed using the Arabic version of 12-item Diabetes Fatalism Scale. Multiple linear regression models were used to assess the relationship between HbA1c and psychosocial and socio-cultural characteristics including diabetes fatalism. Four models were run to examine the independent association between HbA1c and diabetes fatalism and to identify which of the 3 subscales (emotional distress, spiritual coping and perceived self-efficacy) were associated with HbA1c.

Results: The mean age of the participants was 58.24(SD?=?13.48) and the majority were females (53.76%), while 32.73% of the sample had diabetes for more than 10 years. Fully adjusted multiple linear regression models showed that higher scores on diabetes fatalism and the emotional distress subscale (P?=?0.018) were significantly associated with higher HbA1c values. In addition, having diabetes for more than 11 years (P?=?0.05) and a higher number of diabetes complications (P?<?0.001) were associated with higher HbA1c levels. However, advanced age (P?=?0.055), female gender (P?=?0.003), and diabetes education (P?=?0.011) were significantly associated with lower HbA1c levels.

Conclusion: This is the first study in the Arab region that identifies diabetes fatalism as an independent predictor of glycemic control among Lebanese. Future studies should further investigate this construct to guide interventions that can address it for better diabetes outcomes.     

Implementation of Recommendations for Long-Acting Contraception Among Women Aged 13 to 18 Years in Primary Care

ObjectiveClinical specialty societies recommend long-acting reversible contraceptives (LARCs) as first-line contraception for adolescent women. We evaluated whether a combined educational and process improvement intervention enhanced LARC placement in primary care within an integrated health care system.MethodsThe intervention included journal clubs, live continuing education, point-of-care guidelines, and new patient materials. We conducted a retrospective cohort study across 3 time periods: baseline (January 2013?September 2015), early implementation (October 2015–March 2016), and full implementation (April 2016–June 2017). The primary outcome was the proportion of LARCs placed by primary care clinicians among women aged 13 to 18 years compared with gynecology clinicians.ResultsKaiser Foundation Health Plan of Colorado cared for approximately 20,000 women aged 13 to 18 years in each calendar quarter between 2013 and 2017. Overall, LARC placement increased from 7.0 per 1000 members per quarter at baseline to 13.0 per 1000 during the full intervention. Primary care clinicians placed 6.2% of all LARCs in 2013, increasing to 32.1% by 2017 (P < .001), including 45.5% of contraceptive implants. Clinicians who attended educational sessions were more likely to adopt LARCs than those who did not (17.9% vs 6.4% respectively, P = .009). Neither overall LARC placement rates (relative risk, 1.9; 95% confidence interval, 0.7?5.6) nor contraceptive implant rates (relative risk, 3.0; 95% confidence interval, 0.9?9.8) increased significantly in clinicians who attended educational activities.ConclusionsThis multimodal intervention was associated with increased LARC placement for adolescent women in primary care. The combination of education and process improvement is a promising strategy to promote clinician behavior change.     

绵羊脊柱不同节段硬脊膜的结构及力学特点

目的了解绵羊颈、胸、腰段硬脊膜的结构和生物力学特点，为人工硬脊膜的研发提供理论参考。方法取 5 只成年雄性白绵羊，处死后取 C₅、T₁₀ 和 L₃ 平面的硬脊膜分别行组织学 HE 染色观察内部结构并测量硬脊膜厚度，扫描电镜观察硬脊膜内外表面形态，透射电镜观察硬脊膜内部结构并测量各部位硬脊膜胶原纤维直径。取 C₆、C₇、T₁₁、T₁₂、L₄、L₅ 平面的硬脊膜行单轴生物力学测试，测量样本的断裂强度、弹性模量和断裂伸长率。 结果HE 染色示颈、胸、腰段硬脊膜厚度逐渐递减，分别为（268.19±15.91）、（198.16±27.25）、（103.74±21.54）μm，比较差异均有统计学意义（P<0.05）。扫描电镜观察示，硬脊膜内表面胶原纤维较多，细胞较少；外表面则细胞分布较多，且细胞均沿纵轴方向拉伸。透射电镜观察示，硬脊膜内部胶原纤维板层状交织排列，板层内胶原纤维同向排列，板层间胶原纤维相互垂直。颈、胸、腰段硬脊膜胶原纤维直径分别为（68.04±21.00）、（64.54±20.64）、（60.36±19.65）nm，比较差异无统计学意义（P>0.05）。单轴生物力学测试显示，颈段硬脊膜轴向和横向的弹性模量、断裂强度、断裂伸长率比较差异均无统计学意义（P>0.05）；胸段和腰段轴向各指标均显著大于横向（P<0.05）。组间比较：颈、胸、腰段硬脊膜的轴向和横向弹性模量、断裂强度、断裂伸长率，两两比较差异均有统计学意义（P<0.05），呈颈、胸、腰段逐渐减小趋势。颈、胸段硬脊膜轴向弹性模量与横向弹性模量比值显著小于腰段（P<0.05）；颈、胸段间比较差异无统计学意义（P>0.05）。 结论绵羊硬脊膜从头侧向尾侧厚度依次减小；硬脊膜内表面胶原纤维分布较多、细胞较少，而外表面被细胞覆盖；硬脊膜内部胶原纤维板层交替排列，具有明显的各向异性生物力学特点，且从头侧向尾侧各向异性生物力学特点越明显。     

Syngeneic B16-F1 cells are more efficient than allogeneic Cloudman cells as antigen source in DC-based vaccination in the B16-F1 murine melanoma model

A major obstacle to obtaining relevant results in cancer vaccination has been the lack of identification of immunogenic antigens. Dendritic cell (DC)-based cancer vaccines used preventively may afford protection against tumor inoculation, but the effect of antigen choice on anti-tumor protection is not clear. When using irradiated syngeneic tumor cells to load DCs, tumor self-antigens are provided, including tumor-associated antigens (TAAs) and neoantigens generated by tumor mutations. On the other hand, allogeneic tumor cells could only supply shared TAAs. To assess the advantages of each source in protective vaccination, we analyzed in C57BL/6 mice the effect of loading DCs with irradiated syngeneic B16-F1 or allogeneic Cloudman melanoma cells; both cell lines were characterized by whole exome sequencing and RNAseq. Tumor cell components from the two irradiated cell lines were efficiently internalized by DCs, and transported to MHC-class II positive tubulovesicular compartments (MIICs). DCs loaded with allogeneic irradiated Cloudman cells (DC-ApoNec_ALLO) induced a partially effective anti-melanoma protection, although Cloudman and B16-F1 cells share the expression of melanocyte differentiation antigens (MDAs), cancer-testis antigens (CTAs) and other TAAs. DCs loaded with syngeneic B16-F1 cells (DC-ApoNec_SYN) established a more potent and long-lasting protection and induced a humoral anti-B16F1 response, thus suggesting that neoepitopes are needed for inducing long-lasting protection.     

经重睑切口的上睑旋转皮瓣矫正轻中度内眦赘皮疗效观察

目的探讨重睑术中采用经重睑切口的上睑旋转皮瓣矫正轻、中度内眦赘皮的疗效。方法回顾分析 2016 年 7 月—2017 年 10 月，重睑术中采用经重睑切口的上睑旋转皮瓣矫正轻、中度睑板型内眦赘皮合并单睑的 34 例患者（试验组）临床资料；以同期 38 例接受传统“Z”成形内眦开大术联合重睑术患者为对照（对照组）。两组患者年龄及内侧赘皮分度比较，差异无统计学意义（P>0.05）。于术前及术后 6 d、6 个月测量眼裂长度，计算眼裂长度改善程度；参照内眦赘皮矫正标准评价手术疗效。 结果两组患者切口均Ⅰ期愈合，并获随访 6 个月。两组内眦赘皮明显矫正。试验组内眦处无切口；对照组遗留瘢痕，其中 6 例增生明显。术后 6 d 试验组及对照组眼裂长度改善程度分别为 3.63%±0.07%、3.70%±0.05%；术后 6 个月分别为 4.64%±0.09%、4.46%±0.10%；两组比较差异均无统计学意义（t=0.005，P=0.996；t=0.287，P=0.871）。术后 6 个月疗效评价，试验组优 20 例、良 12 例、差 2 例，优良率 94.12%；对照组优 16 例、良 16 例、差 6 例，优良率 84.21%；差异无统计学意义（χ²=0.796，P=0.372）。 结论经重睑切口的上睑旋转皮瓣矫正轻、中度内眦赘皮手术操作简便、效果满意，内眦处无瘢痕形成。