miR-451a suppresses the development of breast cancer via targeted inhibition of CCND2

Extensive research has indicated that miRNAs are crucial for the occurrence and progression of cancers. miR-451a, involved in breast cancer (BC), is one of the miRNAs. This study focused on the mechanism by which miR-451a regulates BC. The levels of miR-451a in BC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan‒Meier analysis showed that this was intimately related to the patient's overall survival rate. Functional experiments revealed the negative effects of miR-451a on the abilities of BC cells to multiply (tested by Cell Counting Kit-8), migrate (tested by wound healing assay), and invade (tested by Transwell assay) and its positive effects on apoptosis (tested by flow cytometry). Western blotting indicated that the expression of tumor-related proteins was affected by miR-451a. Moreover, in vivo experiments suggested that tumor growth was clearly restrained by an miR-451a agonist in a xenograft tumor model. Bioinformatic analysis indicated that miR-451a directly targeted Cyclin D2 (CCND2), as demonstrated by the luciferase reporter assay. An opposite change in the level of CCND2 and miR-451a in BC was indicated by qRT-PCR, western blotting, and immunohistochemistry. Subsequently, functional experiments and western blotting analysis confirmed that CCND2 accelerated BC progression, which was regulated by miR-451a. Cumulatively, research on miR-451a may be valuable for BC treatment.     

Anti-neutrophil antibodies (anti-MPO-ANCAs) are associated with poor prognosis in breast cancer patients

Anti-neutrophil antibodies are capable of activating neutrophils in sterile environments, releasing extracellular traps containing myeloperoxidase (MPO) and anti-MPO antibodies (MPO-ANCAs or anti-MPO-ANCAs), which have been implicated in the pathogenesis of several diseases. The present study evaluated systemic and tumor tissue levels of anti-MPO-ANCAs breast cancer patients, and its relation to clinicopathological characteristics. Anti-MPO-ANCAs were measured in serum and tissue samples of 150 patients by enzyme-linked immunoassay. Samples were pooled according to clinicopathological characteristics of patients. Higher anti-MPO-ANCAs levels were detected in groups presenting negative clinicopathological characteristics, such as high histological grade tumors and risk factors such as body mass index, menopausal status and early onset at diagnosis. The present data highlights anti-MPO-ANCAs as associated to poor prognosis in breast cancer, a role beyond its actually discussed role in autoimmunity and vasculitis.     

基于医院信息系统的乳腺癌临床特征及中西医用药特征分析

目的 解析真实世界中乳腺恶性肿瘤患者的人群特征、诊断特征、中西医用药特征，为乳腺癌的临床防治提供参考。方法 采集2002年2月至2015年5月全国60家三级甲等医 院信息系统（Hospital Information System，HIS）中，出院诊断为“乳腺癌”的患者用药信息，采用SAS9.3统计软件，对人口学信息、诊断信息、医嘱用药信息等进行描述性分析。结果 39798例乳腺癌患者，平均年龄（50.93者，平均年龄）岁；多以门诊入院，入院病情以“一般”为主;合并疾病主要为高血压，骨肿瘤，联用西药以抑制肿瘤细胞增殖、治疗并发症、缓解放化疗不良反应为主；中医辨证以痰瘀互结证，气阴两虚证，肝气淤滞证，脾气亏虚证型最为常见，临床清热解毒剂、益气扶正剂，活血化瘀剂应用较多。结论 乳腺癌中西医结合治疗，联用药物广泛，临床治疗基本符合临床指南。     

附着龈重建应用于口腔种植修复中的临床效果观察

目的探讨附着龈重建应用于口腔种植修复中的临床效果。方法将本院于2016年10月-2018年10月期间收治的行口腔种植修复治疗的附着龈缺失患者82例作为研究资料,依据治疗方案分组,对照组为传统修复治疗方案,观察组采用附着龈重建治疗修复方案,各41例,评价两组术后不同阶段附着龈宽度、龈缘外形及附着点重建改善效果,并评价患者评价治疗满意度。结果术后3个月观察组患者附着龈宽度改善Ⅲ级率56.10%明显高于对照组0.00%,龈缘外形与附着点重建Ⅲ级率60.98%明显高于对照组0.00%(P <0.05);术后6个月观察组患者附着龈宽度改善Ⅲ级率75.61%明显高于对照组0.00%,龈缘外形与附着点重建Ⅲ级率73.17%明显高于对照组0.00%(P <0.05);观察组治疗满意度97.56%与对照组70.73%比较明显更高(P <0.05)。结论针对行口腔种植修复治疗的附着龈缺失患者采用附着龈重建治疗修复方案利于快速恢复附着龈增加宽度,改善龈缘外形及附着点重建效果,获得患者的高度满意度,治疗价值较高。     

Isokinetic flexion strength recovery after ACL reconstruction: a comparison between all inside graft-link technique and full tibial tunnel technique

Introduction: Recently, a new minimally invasive single bundle technique for anatomic ACL reconstruction has been described, called the ‘All-Inside graft-link technique’. One of the advantages of this procedure is the reduced morbidity at the donor site as the graft choice is the quadrupled semitendinosus, thus sparing the gracilis tendon. The aim of this study was to evaluate isokinetic flexion strength recovery in patients who underwent a gracilis sparing technique compared to those with a full-tibial tunnel technique using a doubled gracilis and semitendinosus tendons (DGST) graft.

Methods: Patients were divided into two groups: Group A (22 patients) who underwent ACL reconstruction performed with an All-Inside graft-link technique; Group B (22 patients) who underwent ACL reconstruction with an Out-In technique and DGST graft. At a mean follow-up of 13 months, quadriceps and hamstring isokinetic peak torque deficits were recorded.

Results: In group A, the mean side to side peak torque flexion difference between the operated and non-operated limbs was ?3% and the mean torque at 30° was ?7.5% at high angular velocity (180°/sec); the mean peak flexion torque was 7.2% and the mean torque at 30° was 3.1% at low angular velocity (60°/sec).

In group B, the mean side to side peak flexion torque was ?3.5% and the mean torque at 30° was ?7.6% at high angular velocity (180°/sec); the mean peak flexion torque was ?7.2% and the mean torque at 30° was ?11% at low angular velocity (60°/sec).

A statistically significant difference was found between the two groups at lower angular velocity both for the mean peak flexion torque and the mean torque at 30° (p = 0.009), with better results in the study group.

Discussion/conclusion: Gracilis sparing technique is a minimally invasive technique for ACL reconstruction and yielded a significantly better flexion strength recovery at lower angular velocity compared to a full tibial tunnel technique with DGST for ACL reconstruction.     

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

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.     

Outcome of isolated posterior cruciate ligament reconstruction at mean 6.3-year follow up: a consecutive case series

Objectives: There is a paucity of reporting on surgical outcomes of isolated posterior cruciate ligament reconstruction (PCLR). We hypothesize that isolated PCL injuries failing nonoperative treatment achieve good outcomes and are able to return to sport following PCLR.

Methods: A retrospective analysis was performed to identify patients with isolated PCL injuries that underwent reconstruction between 2001 and 2014. Patients with multi-ligamentous injury or another concomitant knee pathology were excluded. Medical records were reviewed for demographic, clinical and operative data. Patients were contacted for administration of a telephone-based questionnaire which included the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form, Lysholm-Tegner scales, Marx activity scale (MAS), return to sport status, and patient satisfaction instruments.

Results: A total of 15 isolated PCL reconstructions in 14 patients with a mean age of 27.5 years (range 17–43) met the study inclusion criteria; mean follow up was 6.3 years (range 1.4–15.2). Pre-operatively, the primary complaint was knee instability in all patients; on physical examination, lack of a firm end point during posterior drawer testing was found in 93% (14/15) of the knees. In total, 12 of 15 knees underwent transtibial, single-bundle PCLR and three of 15 underwent tibial inlay, double bundle PCLR. Graft types included: quadriceps autograft (7/15), Achilles allograft (6/15), and hamstring autograft (2/15). There were no graft failures in our patient cohort. At most recent follow up the mean scores respectively on the IKDC form, Lysholm-Tegner scales and MAS were (standard deviation): 77.3 (16.5), 83.1 (17.9), 6.13 (2.6), and 7.1 (6.0). All fourteen patients were athletes prior to their injury and 79% (11/14) returned to sport and overall patient satisfaction was 9.2/10.

Conclusions: Isolated PCLR provides good outcomes at mean medium-term follow up with restoration of function, high rate of return to sport and overall patient satisfaction.