Ursolic acid promotes apoptosis,autophagy, and chemosensitivity in gemcitabine‐resistant human pancreatic cancer cells

Gemcitabine (GEM) resistance in pancreatic adenocarcinoma mediated by the receptor for advanced glycation end products (RAGE) has been demonstrated. Therefore, investigating the safety and the potential of new auxiliary methods for pancreatic cancer treatment is urgent. Ursolic acid (UA), a natural pentacyclic triterpenoid found in apple peels, rosemary, and thyme, has been reported to have anticancer capacity. This study aimed to reveal the underlying mechanisms of UA in cell death and drug enhancement, especially in GEM‐resistant pancreatic cancer cells. First, GEM‐resistant cells (MIA Paca‐2^GEMR cells) were established by incrementally increasing GEM culture concentrations. UA treatment reduced cell viability through cell cycle arrest and endoplasmic reticulum (ER) stress, resulting in apoptosis and autophagy in a dose‐dependent manner in MIA Paca‐2 and MIA Paca‐2^GEMR cells. High RAGE expression in MIA Paca‐2^GEMR cells was suppressed by UA treatment. Interestingly, knocking down RAGE expression showed similar UA‐induced effects in both cell lines. Remarkably, UA had a drug‐enhancing effect by decreasing cell viability and increasing cell cytotoxicity when combined with GEM treatment. In conclusions, UA triggered ER stress, subsequently regulating apoptosis‐ and autophagy‐related pathways and increasing GEM chemosensitivity in pancreatic cancer cells by inhibiting the expression of RAGE.     

基于生物量、活性物质积累和抗氧化能力的当归高海拔种植区域选择

目的以根茎生物量、活性物质含量以及抗氧化能力为指标,选择适宜提高当归品质的高海拔种植区域。方法在严格控制种质、水分和土壤养分的条件下,以不同海拔(2 100、2 500和2 900 m)2年生当归根茎为材料,分别对干质量、活性物质含量以及抗氧化能力进行测定与分析。结果高海拔虽不能促进当归根茎生物量,却显著提高了活性物质的积累量和抗氧化能力;以单株积累量计算,2 900 m未抽薹当归根茎中阿魏酸、可溶性糖、酚和黄酮类含量分别为2 100 m植株的2.06、1.13、1.34和1.15倍;体外抗氧化能力也随海拔升高逐渐增加。综合分析表明,在2 100～2 900 m海拔内,未抽薹当归根茎中活性物质的总积累量(干质量和单株)均随海拔升高逐渐增加。结论提升当归种植海拔高度可显著提高根茎活性物质量;活性物质生物合成与积累受到低温和光照的综合调控。该研究结果将为提高当归产量和品质以及大面积种植栽培提供理论基础与依据。     

Protective role of histone deacetylase 4 from ultraviolet radiation-induced DNA lesions

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.     

前列腺素E联合连续肾替代治疗对脓毒症合并急性肾损伤预后的影响

目的：探讨前列腺素E联合连续肾替代治疗（CRRT）对脓毒症合并急性肾损伤（AKI）患者预后的影响。方法：选取89例脓毒症合并AKI患者为研究对象，采用随机数字表法分为对照组（n=44）和观察组（n=45），分别采取CRRT及前列腺素E联合CRRT治疗。比较2组患者预后转归情况，检测并比较2组患者治疗前后血清炎性因子、肾功能及免疫功能指标。结果：观察组ICU治疗时间及住院时间较对照组明显缩短（P<0.05）；对照组死亡14例（31.82%），观察组死亡9例（20.00%），2组患者死亡率无明显差异（P>0.05）。与治疗前比较，治疗后2组血清TNF-α、IL-6、hs-CRP含量降低，BUN、SCr含量升高（P<0.05），且观察组上述指标均低于对照组（P<0.05）。与治疗前比较，治疗后2组CD4⁺/CD8⁺及观察组NK细胞比例及IgG、IgA、IgM含量均明显升高（P<0.05），且观察组高于对照组（P<0.05）。与治疗前比较，治疗后2组Marshall评分、APACHEⅡ评分下降（P<0.05），且观察组低于对照组（P<0.05）。结论：前列腺素E联合CRRT治疗脓毒症合并AKI可显著降低患者炎性因子水平，改善患者肾功能和免疫功能，效果优于单独CRRT治疗。     

SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters

Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI-121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3-deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6- and/or ITGAM-deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin-mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3-H3K4me3-integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface.     

实时三维经胸超声心动图联合术中经食管超声心动图在二尖瓣病变的临床应用

目的 探讨实时三维经胸超声心动图联合术中经食管超声在二尖瓣病变手术患者中的应用。 方法 回顾性分析明确诊断为二尖瓣瓣膜病并行二尖瓣病变手术患者40例，其中儿童患者7例，成年患者33例，分别于术前及术后3个月测量入组患者的左心房前后径（anteroposterior diameter of left atrium，LAAPD）、左心室射血分数（left ventricular ejection fraction，LVEF）、左心室舒张末期内径（left ventricular end-diastolic diameter，LVEDD）、二尖瓣病变等情况。 结果 与术前相比，儿童及成年组患者术后3个月的LAAPD、LVEDD均明显减小，且仅成年组患者术后的LVEF值明显增加，差异有统计学意义(P＜0.05)，术后3个月进行随访时显示，儿童及成年组患者术后二尖瓣返流例数均较术前明显减少,差异有统计学意义(P＜0.05)，二尖瓣返流量（mitral regurgitation，MR）分级与术式呈正相关。 结论 实时三维经胸超声心动图联合术中食管超声具有无创、操作简便、省时等优点，在二尖瓣病变的应用中发挥着极其重要的作用，能够在术前准确显示瓣膜病损部位、程度，并指导术式选择。     

妊娠合并肺动脉高压患者剖宫产围产期并发症的危险因素分析

目的探讨妊娠合并肺动脉高压患者剖宫产围产期并发症的危险因素。方法该研究为病例对照研究。回顾性纳入山东大学齐鲁医院、山东第一医科大学附属省立医院、山东省千佛山医院和青岛大学附属医院2010年5月至2020年5月妊娠合并肺动脉高压患者。根据是否发生剖宫产围产期并发症分为并发症组和对照组。收集患者的一般临床资料和辅助检查结果, 记录患者发生围产期并发症的情况。围产期并发症包括心功能恶化、新发心律失常、心脏骤停、术后42 d内全因死亡、产后出血及血栓事件。采用多因素logistic回归模型分析妊娠合并肺动脉高压患者剖宫产围产期并发症的危险因素。结果研究纳入患者167例, 年龄28(24, 32)岁, 其中并发症组47例, 对照组120例。两组患者年龄, 孕周, 初产妇、存在心内分流及接受靶向药物治疗者比例, 左、右心室舒张末期内径差异均无统计学意义(P均>0.05)。与对照组比较, 并发症组患者特发性肺动脉高压者比例较高(P=0.001)、接受全身麻醉的比例较高(P=0.001)、超声心动图估测的肺动脉收缩压较高(P<0.001)、术前世界卫生组织(WHO)功能Ⅲ/Ⅳ级者比例较高(...     

地方医学院校课程质量监控体系的构建探索

基于国家深化高等院校课程建设的新时代视域，提升课程质量成为高校教育教学发展的重要任务。地方医学院校作为基层卫生人才的培养摇篮，构建科学合理的课程质量监控体系愈发迫切。本文分析了我国高等院校课程质量监控体系存在的问题，结合地方医学院校办学特点和广州医科大学工作实践，探索构建了集“多样化监控方法、全维度监控指标、闭环式反馈机制、多层级文化建设”为一体的课程质量监控体系，为同类院校提供实际参考。     

孤独症谱系障碍疼痛敏感程度及机制的研究进展

精神分裂症的主观生活质量反映了患者对个人身体、心理、社会和行为功能的满意度，为 精神卫生系统提供了一个评价临床疗效的主观指标。现回顾精神分裂症主观生活质量的评估工具和影 响因素，为改善患者主观生活质量的实践提供参考     

基因组拷贝数变异测序与染色体核型分析在胎儿遗传学诊断中的比较

目的比较基因组拷贝数变异测序(CNV-seq)技术和染色体核型分析和在产前胎儿遗传学诊断中的应用价值。方法收集来我院有产前诊断指征进行羊水穿刺的259例孕妇,取材后,送检染色体核型分析和CNV-seq,比较两种方法在产前诊断中的优缺点。结果259例标本中,共诊断异常染色体核型及微缺失微重复23例,总阳性诊断率8.88%(23/259),CNV-seq结果显示,共有22例染色体拷贝数异常(12例三体+9例微缺失微重复+1例三倍体),检出率为8.49%;染色体核型分析结果显示为:17例染色体异常(12例三体+3例结构异常+1例嵌合型+1例三倍体),检出率为6.56%。此外还检出染色体多态7例。结论CNV-seq与染色体核型分析对于染色体非整倍体的检测效力一致,CNV-seq能检测染色体微缺失微重复,染色体核型分析则能诊断出三体具体核型,在怀疑性染色体异常时,建议行两者联合检测。