Recent studies have shown human platelets can access the tumor microenvironment by passive diffusion across capillaries or via activated immune cells. In a previous study, we exploited this affinity of platelets for tumor cells as part of a new approach to target tumors with modified platelets. Therefore, the engineering of human nanoplatelets as living vehicles for in vivo tumor-targeted near-infra-red fluorescence (NIRF) imaging and the delivery of cytotoxins to tumor cells by endocytosis are described in this study. Nanoplatelets with an average diameter of 200 nm were prepared by mild sonication of kabiramide C (KabC)-loaded human platelets. The sealed plasma membrane of the nanoplatelets allows them to accumulate and retain membrane-permeable chemicals, such as epidoxorubicin (EPI) and KabC. Tumor-targeted imaging functionalities were engineered on the nanoplatelets by surface-coupling transferrin, Cy5 and Cy7. High-resolution fluorescence imaging and flow cytometry analyses showed that the nanoplatelets loaded with EPI and Cy5 targeted human myeloma cells (RPMI8226 cells) that over-expressed the transferrin receptor. The endocytosis of the nanoplatelets by RPMI8226 cells was transferrin-dependent and induced apoptosis. The test results also showed that the nanoplatelets functionalized with transferrin and Cy7 and injected in mice bearing RPMI8226 cells-derived myeloma xenotransplants accumulated in the tumor tissue and could be used for high-contrast in vivo NIRF imaging of early-stage tumors. Nanoplatelets represent a new class of living nano-vehicles that may efficiently target and deliver therapeutic agents and imaging probes to diseased tissues including tumors.

Taper implants differ greatly from anatomical teeth in shape. In this study, seven three-dimensional finite element models were established, including a conventional taper implant and six root-analog implants with different root numbers and shapes. Vertical, horizontal, and oblique instantaneous loads of 100 N were applied to the models to obtain stress distribution in the implant, mucosa, cortical bone, and cancellous bone. ANSYS was used to perform the analysis under hypothetical experimental conditions. We find the stresses in all the implants and surrounding tissues varied by loading direction, the sequence of stress magnitude is vertical load, oblique load, and then horizontal load. The maximum stress values in root-analog implants were significantly less than in the taper implant. Moreover, stress distribution in the former was equalized contrary to the concentrated stress in the latter. Root-analog implants with different root geometry also revealed a pattern: stresses in multiple-root implant models were lower than those in single-root implants under the same load. The implant with a long and rounded root distributed the stress more uniformly, and it was mainly concentrated on the implant itself and cancellous bone. However, the opposite effect was observed in the short implant on mucosa and cortical bone. The root geometry of anatomical teeth can modify their functions. A uniform-shaped implant can hardly meet their functional requirements. Thus, the root-analog implant could be a possible solution.

Lower extremity arterial disease (LEAD) is a major vascular complication of diabetes. Vascular endothelial cells dysfunction can exacerbate local ischemia, leading to a significant increase in amputation, disability, and even mortality in patients with diabetes combined with LEAD. Therefore, it is of great clinical importance to explore proper and effective treatments. Conventional treatments of diabetic LEAD include lifestyle management, medication, open surgery, endovascular treatment, and amputation. As interdisciplinary research emerges, regenerative medicine strategies have provided new insights to treat chronic limb threatening ischemia (CLTI). Therapeutic angiogenesis strategies, such as delivering growth factors, stem cells, drugs to ischemic tissues, have also been proposed to treat LEAD by fundamentally stimulating multidimensional vascular regeneration. Recent years have seen the rapid growth of tissue engineering technology; tissue-engineered biomaterials have been used to study the treatment of LEAD, such as encapsulation of growth factors and drugs in hydrogel to facilitate the restoration of blood perfusion in ischemic tissues of animals. The primary purpose of this review is to introduce treatments and novel biomaterials development in LEAD. Firstly, the pathogenesis of LEAD is briefly described. Secondly, conventional therapies and therapeutic angiogenesis strategies of LEAD are discussed. Finally, recent research advances and future perspectives on biomaterials in LEAD are proposed.

Gastric cancer is a kind of gastrointestinal tumor with high morbidity and mortality. Finding effective methods for early diagnosis and treatment of gastric cancer has important significance and application prospects. MicroRNAs without protein coding potential affect the occurrence and development of gastric cancer. This study aims to explore the biological function and mechanism of microRNA-107 (miR-107) in gastric cancer. The results show that miR-107 is low expressed in gastric cancer, while TRIAP1 is highly expressed; the overexpression of miR-107 can inhibit the progression of gastric cancer in vivo and in vitro, while the overexpression plasmid of TRIAP1 can restore the miR-107 mimic-induced cell proliferation and metastasis inhibition, and the small interfering RNA of TRIAP1 can inhibit the cell proliferation and invasion induced by miR-107 inhibitor. In conclusion, the results of this study show that miR-107 can inhibit the proliferation of gastric cancer in vivo and in vitro by targeting TRIAP1.

胃癌是一种常见的恶性肿瘤,总体生存率低,治疗手段局限.缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)是帮助细胞适应缺氧环境的关键转录因子,广泛调节缺氧基因表达,协调影响肿瘤发生的多种信号分子活动,在参与调节肿瘤细胞命运中发挥着重要作用.过去的二十年中,胃癌及HIF-1在胃癌中的影响机制进行广泛的研究,HIF-1已经成为一个有前途的抗癌治疗靶点.本文就近年来HIF-1在胃癌中的研究进展作一简要综述.

BACKGROUND:GPRC5A is associated with various cancer initiation and progression. Controversial findings have been reported about GPRC5A prognostic characteristics, and no meta-analysis has been conducted to assess the relationship between GPRC5A and cancer prognosis. Therefore, the objective of this meta-analysis is to evaluate the overall prognostic effectiveness of GPRC5A. METHODS:We first conducted a systematic search in the PubMed, Embase, Web of Science, CNKI, Cochrane, and WangFang databases. The hazard ratio (HR) and odds ratios (OR) with 95% CI were then pooled to assess the associations between GPRC5A expression and overall survival (OS), disease-free survival (DFS), event-free survival (EFS), and clinicopathological characteristics. Chi-squared test and I2 statistics were completed to evaluate the heterogeneity in our study. A random-effects model was used when significant heterogeneity existed (I2>50% and p<0.05); otherwise, we chose the fixed-effect model. Subgroup analysis was stratified by tumor type, region, HR obtained measurements, and sample capacity to explore the source of heterogeneity. RESULTS:In total, 15 studies with 624 patients met inclusion criteria of this study. Our results showed that higher expression of GPRC5A is associated with worse OS (HR:1.69 95%CI: 1.20-2.38 I2 = 75.6% p = 0.000), as well as worse EFS (HR:1.45 95%CI: 1.02-1.95 I2 = 0.0% p = 0.354). Subgroup analysis indicated that tumor type might be the source of high heterogeneity. Additionally, cancer patients with enhanced GPRC5A expression were more likely to lymph node metastasis (OR:1.95, 95%CI 1.33-2.86, I2 = 43.9%, p = 0.129) and advanced tumor stage (OR: 1.83, 95%CI 1.15-2.92, I2 = 61.3%, p = 0.035), but not associated with age, sex, differentiation, and distant metastasis. CONCLUSION:GPRC5A can be a promising candidate for predicting medical outcomes and used for accurate diagnosis, prognosis prediction for patients with cancer; however, the predictive value of GPRC5A varies significantly according to cancer type. Further studies for this mechanism will be necessary to reveal novel insights into application of GPRC5A in cancers.

Tumour-associated macrophages (TAMs) are thought to contribute to oral squamous cell carcinoma (OSCC) initiation and progression. However, the underlying mechanism through which TAMs foster OSCC progression is still unclear. This study intended to determine whether there are exclusively exosomal miRNAs-derived macrophages that are functionally necessary for OSCC progression. The phenotype of TAM recruitment in OSCC tissue samples was assessed, subsequently identifying the influence of M2 macrophages and exosomes derived from M2 macrophages on OSCC proliferation and tumorigenesis in vitro and in vivo. CD68 and CD163, the specific markers of M2 type macrophages, were upregulated in TAMs presented in intra-cancer tissues. M2 macrophages and M2 macrophage-derived exosomes (M2 exos) both can promote OSCC growth and tumorigenicity. An exosomal RNA-seq analysis was conducted to predict regulatory exosomal miRNAs related to OSCC growth, which determined miR-31-5p and LATS2 for subsequent experiments. Mechanistically, miR-31-5p was delivered to recipient OSCC cells through M2 exos and complementary pairing with the large tumor suppressor 2 (LATS2) coding sequence, thus suppressing the expression of LATS2 and inactivation the Hippo signaling pathway to support OSCC growth. Collectively, our findings demonstrate that M2 macrophage-derived exosomal miR- 31-5p can make tumor suppressor LATS2 gene inhibited and facilitate the progression of OSCC via inhibiting the Hippo signaling pathway, which possibly provides new targets for the molecular therapy of OSCC.

目的 了解乳腺癌相关淋巴水肿患者患肢组织水分比率的影响因素.方法 采用方便抽样法,抽取本院乳腺中心150例乳腺癌相关淋巴水肿患者作为研究对象,调查其一般资料、疾病相关信息及患肢组织水分比率等.结果 乳腺癌相关淋巴水肿患者患肢组织水分比率为(38.80％±1.07％).多重线性回归分析显示,体脂肪率、肿瘤分期及淋巴结清扫数目是乳癌相关淋巴水肿患者患肢组织水分比率的影响因素(P<0.05),共同解释其54.30％的变异.结论 体脂肪率越高,肿瘤分期越晚,淋巴结清扫数目越多,乳腺癌相关淋巴水肿患者患肢组织水分比率越高,水肿程度越大.

To observe whether different insulin glargine titration algorithms based on fasting blood glucose (FBG) levels lead to different glycaemic variations (GVs) in type 2 diabetes (T2D) patients, a prospective, randomized, single-centre, comparative, three-arm parallel-group, open-label, treat-to-target, 24-week study was performed. A total of 71 uncontrolled T2D patients were recruited and randomized 1 : 3 : 3 into Groups 1, 2, and 3 (insulin titration goals of FBG ≤ 5.6, ≤6.1, and ≤7.0) for this study. The initiated insulin glargine dose was recommended at 0.2 U/kg/day and was then titrated following the FBG target. Patients were subjected to two 3-day continuous glucose monitoring (CGM) at baseline and the endpoint, wherein the CGM data were analysed, and the study's primary endpoint was the difference in 24 hrs mean amplitude of glycaemic excursion (MAGE) among the three groups. We observed that patients in the three groups had similar MAGE levels at the endpoint; however, Group 2 achieved a significant decrease in the MAGE level from baseline to the endpoint as compared to Groups 1 and 3 (all p < 0.05). We also observed that these patients had significant glycated haemoglobin A1c (HbA1c) value improvements as compared to the other two groups (all p < 0.05). Therefore, choosing an FBG level of 6.1 mmol/L as an insulin titration target provided significant GVs and HbA1c value improvements in T2D patients. Moreover, our data indicated that an FBG of 6.1 mmol/L could possibly be an insulin glargine titration target in T2D patients.

目的:了解口腔专科医院护理人员对锐器盒使用基本知识的知晓情况及锐器盒临床实际使用情况,为锐器盒在口腔专科医院的临床规范使用提出建议和对策.方法:选取南京医科大学附属口腔医院在职的护师及主管护师各50名为调查对象,通过问卷调查了解锐器盒的使用现状和存在问题,对调查资料进行统计分析.结果:主管护师和护师对锐器盒使用培训参加率分别为78.1％和61.8％;对20种常见口腔医疗废物中损伤性废物的完全正确辨识率仅为9.6％和2.2％;对于锐器盒安全特性内涵知晓情况主要集中于部分知晓,完全知晓率分别为15.8％和8.7％;锐器盒在两类职称的护理人员中规范使用率仅为40.5％和38.2％;影响锐器盒使用的最主要原因分别为成本因素(49.4％)和缺乏专人管理(22.5％).结论:虽然两类职称的护理人员都参加过有关培训,但培训的质量和效果有待提高;锐器盒的临床可见率尚可,但规范使用率较低,锐器盒在口腔专科医院的规范使用和管理仍有待进一步的加强.

目的 探讨姑息性手术对Ⅳ期SiewertⅡ型食管胃结合部腺瘤(AEG)患者预后的影响.方法 通过SEER*Stat软件收集2004—2015年病理诊断为Ⅳ期SiewertⅡ型AEG的病例4337例,其中手术组患者341例,非手术组患者3996例.运用倾向得分匹配(PSM)平衡组间差异,采用Cox比例风险模型、Kaplan-Meier分析研究患者的预后特点.结果 Cox单因素分析发现,手术、年龄、放疗、化疗、肿瘤T分期以及分化程度均可能是影响Ⅳ期SiewertⅡ型AEG患者预后的相关因素(P﹤0.05).Cox多因素分析显示,手术、化疗、分化程度Ⅲ～Ⅳ级、T4期、高龄均是患者的总生存(OS)和肿瘤特异性生存(CSS)的危险因素.Kaplan-Meier生存曲线分析提示,手术组患者OS与CSS均优于非手术组(P﹤0.05).结论 姑息性手术可以改善Ⅳ期SiewertⅡ型AEG患者OS及CSS,推荐晚期患者采取姑息性手术联合全身化疗的治疗策略.

Lu Dai Nanjing Medical University Second A liated Hospital Xiao Jin Nanjing Medical University Second A liated Hospital Jiayan Wang Nanjing Medical University Second A liated Hospital Yilan Ma Nanjing Medical University Second A liated Hospital Haihao Yan Nanjing Medical University Second A liated Hospital Ye Jin Nanjing Medical University Second A liated Hospital Xiaojuan Zhu Nanjing Medical University Second A liated Hospital Zheng Liu (  liuzheng117@njmu.edu.cn ) Nanjing Medical University Second A liated Hospital

Clinical and investigational proof indicates that tumour-related macrophages stimulate tumour initiation and development. Consequently, macrophage-derived molecular factors controlling OSCC initiation are not yet completely understood. Here, we show that M2 macrophage–regulated OSCC cell growth and tumorigenicity depend on M2 macrophage-derived exosomes (M2 exo). M2 exo exhibited a high level of miR-31-5p, and the M2 exo-mediated increase in OSCC cell proliferation and growth depended on this miRNA. Mechanistically, miR-31-5p was delivered to OSCC cells through M2 exo and complementary pairing with the LATS2 coding sequence, thus suppressing the expression of LATS2, which has been considered to be a major aspect inhibiting OSCC growth. Collectively, our findings demonstrate that M2 exo participate in OSCC tumorigenesis, and M2 exo mediate their tumour-inducing effect via the miR-31-5p/LATS2 axis of the Hippo signalling pathway in OSCC. This active and mutual communication among OSCC cells and M2 macrophages provides a novel strategy for treating OSCC. Funding Statement: This work was supported by research grants from the National Natural Science Foundation of China (21872026), the Outstanding Young scholar Foundation of Jiangsu Province, China (BK20170106), the Major Projects of Science and Technology Development Fund of Nanjing Medical University (NMUD2019001), the Open Fund of State Key Laboratory of Pharmaceutical Biotechnology, Nan-jing University, China (KF-GN-201903), the Southeast University and Nanjing Medical University Cooperative Research Project, China (2019DN0003), the Open Research Fund of State Key Laboratory of Bioelectronics, Southeast University. Declaration of Interests: None. Ethics Approval Statement: The study procedure was under the approval of the Ethics Committee of Stomatology Hospital Affiliated to Nanjing Medical University, and written informed consent was obtained from every patient.

Background: YAP is a protein encoded by the YAP gene in humans. Numerous studied showed that YAP expressed in colorecal carcinoma (CRC) and has a association with poor clinical outcomes. However, the association between YAP expression level with prognostic and clinicopathological features in CRC patients remains unclear. Therefore, we performed a meta-analysis to investigate the prognostics effect of YAP expression on CRC patients. Methods: A systematic search of the PubMed, Web of Science, Cochrane Library and Embase databases was conducted based on predefined selection criteria in April 26, 2020. The correlation between YAP expression level and survival outcomes or clinicopathological characteristic was analyzed by hazard ratios (HR) or odds ratios (OR) at 95% confdence intervals (CI). Results: 12 studies were included, with a total of 2286 CRC patients,in our meta-analysis.the results show the relationship between YAP expression level with overall survival (OS) in CRC patients HR (2.02, 95%CI 1.67-2.44 I 2 =19.7% P= 0.25) . In addition to clinicpathological features, CRC patients with overexpression of YAP were tend to advanced TNM stage(OR:2.99, 95%CI 2.11-4.25, I2=0.0%, P=0.699), lymph node metastasis(OR:3.73, 95% CI 2.63-5.30, I2=4.8%, P=0.386), distant metastasis(OR:3.03, 95% CI 1.21-7.56, I2=65.3%, P=0.021), tumor invasion depth HR (2.82 95%CI 1.65-4.83 I2=0.0%, p=0.413), but have no associated with sex, tumor size, tumor location and tumor differentiation. Conclusion: The results of this meta-analysis show that high expression of YAP tended to have a worse progosis and have great influence on clinicpathological features. which means YAP may serve as a promising indicator in the prediction of prognosis and clinicopathological features in CRC patients.

Background : An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and potential mechanisms of HOX proteins in GC. Methods : A comprehensive search of PubMed, EMBASE, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement . The pooled hazard ratio (HR) with its 95% confidence interval (95% CI ) and the pooled odds ratio (OR) with its 95% CI were used to assess the effects of HOX protein expression on the prognosis and clinicopathological features of GC, respectively. Results : Nineteen studies involving 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I 2 =90.5%, p=0.000). According to the subgroup analysis, increased expression of HOX proteins in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36-0.59, I 2 =3.1%, p=0.377), while the overexpression of HOX proteins in the upregulated subgroup correlated with a reduced OS (pooled HR: 2.59, 95% CI: 1.79-3.74, I 2 =73.5%, p=0.000). The aberrant expression of HOX proteins was crucially related to the TNM stage, depth of tumour invasion, tumour size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in patients with GC . In addition , the molecular mechanisms by which HOX proteins regulate the tumorigenesis and development of GC were also explored. Conclusions : HOX proteins play vital roles in GC progression and might serve as prognostic markers for GC. Novel therapeutic strategies targeting HOX proteins are promising for GC prevention and therapy.

Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide and is characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1 alpha (HIF-1α) is a major regulator of cellular response to changes in oxygen concentration, supporting the adaptation of tumor cells to hypoxia in an oxygen-deficient tumor microenvironment. Numerous studies revealed the central role of HIF-1α in the carcinogenesis and progression of pancreatic cancer. This article reviewed the molecular mechanisms of how HIF-1α regulated tumorigenesis and progression of pancreatic cancer and suggested that targeting HIF-1α and its signaling pathways could be promising therapeutics for pancreatic cancer.

As a widely used first-line chemotherapy drug for tumor, Doxorubicin (DOX) can induce various side effects on normal tissues because of its non-specific distribution in the body. Emerging evidence has shown that platelets have the capability to recognize and interact with tumor cells. Inspired by this, the platelet-based drug delivery system was constructed by loading of DOX in platelet cytoplasm and modification of transferrin on the surface of platelet (Tf-P-DOX). The encapsulation efficiency of DOX in platelet was the highest at the DOX concentration of 0.05 mM, and reached to 64.9%. Fluorescence microscopy showed that the Tf-P-DOX facilitated cell uptakes and enhanced intracellular drug accumulation in B16F10 cells. Compared with free DOX, Tf-P-DOX exhibited an enhanced effect on cell apoptosis at the same concentration of DOX. In vivo imaging system showed that the near-infrared fluorescence of B16F10 tumor-bearing mice was mainly accumulated in the tumor site, which caused the inhibition of tumor growth in mice. The morphological changes of tumor tissue in Tf-P-DOX group was significant in comparison with those of the control group, including the small nucleus, the insufficiency of cancerous nest, and the infiltration of inflammatory cells, while Tf-P-DOX did not show significant adverse effects on normal tissues. Compared with the control group, the levels of caspase 9 and caspase 3 protein expressions were increased significantly in Tf-P-DOX group. Our studies suggest platelets can be repurposed as promising carriers for efficient targeting and treatment of solid tumors.

Aims: Considering the insulin sensitivity may increase by exercise particularly in patients with type 2 diabetes (T2D), glycemic variation during exercise needs to be studied when the patients are treated with insulin. This study aimed to explore the influence factors of the efficacy and safety of aerobic exercise in patients with T2D treated with Continuous Subcutaneous Insulin Infusion (CSII). Methods: A total of 267 patients with T2D, treated with CSII, were included. Glycemic variations were assessed by continuous glucose monitoring (CGM). Patients were asked to complete 30 min aerobic exercise for at least one time during CGM. The patients were divided into effective and ineffective group by incremental glucose area under curve from 0 to 60 min after exercise (AUCO-60 min). Results: The patients completed a total of 776 times of aerobic exercises. Blood glucose decreased fastest in the first 60 min of exercise. Pre-exercise blood glucose (PEBG) was negatively correlated with AUC(0-60min) (standardized beta = -0.386, P < 0.001) and incremental AUC of blood glucose < 4.4 mmol/L (standardized beta = -0.078, P = 0.034), and was significantly higher in effective group than in ineffective group (P < 0.001). The Aglucose AUC(0-60min) during post-dinner was significantly higher than that during pre-lunch, post-lunch and predinner (P < 0.05 for all). Conclusions: PEBG is positively correlated with efficacy of aerobic exercise. Aerobic exercise will not worsen hyperglycemia when the PEBG > 16.7 mmol/L. Post-dinner exercise decreases the blood glucose better than other periods of the day. (C) 2018 Elsevier B.V. All rights reserved.