Nanotherapy: New Approach for Impeding Hepatic Cancer Microenvironment via Targeting Multiple Molecular Pathways

Objective: Hepatocellular carcinoma (HCC) microenvironment has been recognized as a key contributor for cancer progression, metastasis, and drug resistance. The crosstalk between tumor cells, the vascular endothelial growth factor (VEGF), and the chemokine (C-C motif) ligand 2 (CCL2) signaling networks mediates immunoinhibitory impact and facilitates tumor angiogenesis. The current investigation aimed at exploring the potent anti-cancer activity of the newly designed nano-based anti-cancer therapy comprising anti-VEGF drug, avastin (AV), and CCR2 antagonist (CR) to counteract HCC and tracking its mode of action in vivo. Methods: The prepared AV, CR, and AVCR nanoprototypes were characterized by nanoscale characterization techniques in our previous work. Here, they are applied for unearthing their anti-cancer properties / mechanisms in hepatic cancer-induced rats via analyzing protein levels and genetic expression of the elements incorporated in the angiogenesis, apoptosis, and metastasis signalling pathways. Results: The present results revealed a significant down-regulation in the angiogenesis, survival and metastasis indices along with up-regulation in the pro-apoptotic mediators upon treatment of hepatic cancer-bearing rats with the novel synthesized nanomaterials when compared with the untreated counterparts. We showed across HCC model that anti-VEGF in combination with CCR2 antagonism therapy leads to sensitization and enhanced tumor response over anti-VEGF or CCR2 antagonism monotherapy, particularly in its nanoscale formulation. Conclusion: The present approach provides new mechanistic insights into the powerful anti-hepatic cancer advantage of the novel nanoprototypes which is correlated with modulating critical signal transduction pathways implicated in tumor microenviroment such as angiogenesis, apoptosis and metastasis. This research work presents a substantial foundation for future studies focused on prohibiting cancer progression and recovery by targeting tumor microenviroment.     

Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.     

脾脏ARFI弹性联合血小板计数预测乙肝肝硬化食管静脉曲张的价值

目的 本研究应用声辐射力脉冲成像(Acoustic Radiation Force Impulse ARFI)技术对慢性乙型肝炎肝硬化患者进行脾脏弹性检测和分析,探讨和对比脾脏ARFI弹性及脾脏ARFI弹性联合血小板计数(Platelet Count PC)在预测乙肝肝硬化食道静脉曲张的临床应用价值。方法 对232例慢性乙型肝炎肝硬化患者应用ARFI技术检测脾脏实时超声弹性,并测量PC,所有患者均于检测前后一周内行胃镜检查明确食管静脉曲张情况,以胃镜结果为金标准,应用受试者工作特征(receiver operating characteristic, ROC)曲线比较脾脏ARFI弹性、PC、及脾ARFI弹性联合PC诊断肝硬化食管静脉曲张的临床价值。结果 食道静脉曲张组脾脏ARFI弹性和PC分别为3.52(3.16-3.87)m/s 和62(41-88.25),无食道静脉曲张组脾脏ARFI弹性和PC分别为2.91(2.35-3.35)m/s和129.5(87.25-196.25)。脾脏ARFI弹性和PC在两组间比较的差异均具有统计学意义(P＜0.001 )。单独脾脏ARFI弹性及脾脏ARFI弹性联合PC的ROC曲线下面积分别为0.76和0.83,差异具有统计学意义(P = 0.0021)。结论 脾脏ARFI弹性测值联合PC较单纯脾脏ARFI弹性能更准确的无创预测慢性乙型肝炎肝硬化食管静脉曲张的存在,具有良好的临床应用前景。     

The retrospective study for effectiveness of cervical cerclage in preventing recurrent preterm birth

ObjectiveThis study aimed to clarify the effectiveness of cervical cerclage in preventing recurrent preterm births.Materials and methodsA retrospective study was conducted using the perinatal registration database of the Japan Society of Obstetrics and Gynecology for the Perinatal Center from 2014 to 2016. The efficacies of history-indicated, ultrasound-indicated, and physical examination-indicated cerclage as preventive treatments for women with a history of preterm birth were evaluated by comparing cerclage and non-cerclage cases. Fisher's exact test was performed to evaluate any significant differences in patient backgrounds. Prior to the evaluation, propensity score matching was performed for history-indicated and ultrasound-indicated cerclage patients.ResultsFor this study, 6060 multiparous women with a history of preterm birth were reviewed. After excluding 17 patients with unknown indications for cervical cerclage, 6043 patients were included in the study. History-indicated and ultrasound-indicated cerclage did not reduce the risk of preterm birth in subsequent pregnancies for any of the pregnancy periods (p = 0.413, p = 1.000). In contrast, physical examination-indicated cerclage significantly reduced the risk of subsequent preterm births for all pregnancy periods (p < 0.001).ConclusionSubsequent preterm births were effectively prevented only in physical examination-indicated cerclage cases. For history- or ultrasound-indicated cerclage, statistically significant differences in subsequent preterm births were not evident.     

奥美拉唑的不良反应及其与其他药物间的相互作用研究

目的探究奥美拉唑所引起的不良反应及其与其他药物间的相互作用。方法122例接受奥美拉唑治疗并出现不良反应的患者,分析患者所处的环境状况、情绪状况、过敏史、年龄、过敏体质、生活习惯、饮酒情况等临床资料,探讨不良反应的发生原因,并分析不良反应累及系统分布情况及临床症状、导致不良反应的药物使用类型以及预后情况。结果122例奥美拉唑所致不良反应患者中,男性患者、年龄40~50岁、过敏体质、过敏史、情绪不稳定、药后饮酒、环境状况差占比相对较高。122例患者奥美拉唑所致不良反应中免疫系统占27.87%、消化道系统占23.77%、心脑血管系统占7.38%、神经系统占9.02%、血液系统占21.31%、肝胆系统占10.66%。患者常见临床症状为皮疹、瘙痒、皮炎、过敏性休克、恶心、呕吐、腹泻、心动过速、心律不齐、头晕、头痛、意识模糊、血小板下降、白细胞减少、血尿、肝功能障碍等。奥美拉唑与抗癫痫药苯妥英、抗惊厥药卡马西平、抗焦虑抗癫痫药地西泮以及安替比林药物相互作用,会使机体代谢功能降低,其发生可能与抑制钠离子内流有关。结论奥美拉唑所致不良反应会累及机体多个系统,因此医护人员应加强对患者的问诊,了解患者的相关情况,设计合理的用药方案,减少不良反应的发生。     

从湿论治慢性静脉功能不全刍见

慢性静脉功能不全是常见的周围血管疾病。文章在梳理历代中医辨证思路的基础上,结合现代医学的认识和临床观察,分别从湿的来源、湿在慢性功能不全疾病中的具体体现和治疗3个方面来探讨本类疾病与湿的关系。认为湿作为本病的重要致病因素和病理产物,贯穿于本病的始终,与本病的形成密不可分,在治疗上应注重对湿的辨析,明确其性质、来源、病证特点等,选用多法以祛湿。