关节镜下四袢与双袢固定修复急性肩锁关节Rockwood V型脱位疗效对比研究

目的对比评估双骨道四袢与单骨道双袢固定修复急性肩锁关节Rockwood Ⅴ型脱位疗效。 方法回顾性分析2010年5月至2016年5月于深圳大学第一附属医院接受关节镜下双骨道四袢与单骨道双袢固定修复急性肩锁关节Rockwood Ⅴ型脱位的所有患者,其中入选82例手术患者,四袢双骨道组与双袢单骨道组各41例。术后2年内随访观察患者的视觉模拟评分（visual analogue scale,VAS） 、患者恢复运动时间、恢复运动患者数量、Constant功能评分、Karlsson肩锁关节功能评分,并通过影像学观察评估喙锁关节和肩锁关节的间隙。 结果术后2年内末次随访X线片显示四袢双骨道组患侧平均喙锁关节和肩锁关节的间隙与双袢单骨道组对比明显减小,且差异具有统计学意义（P<0.05）;双袢单骨道组患者健侧平均喙锁关节和肩锁关节的间隙与患侧对比明显减小,且差异具有统计学意义（P<0.05）;然而四袢双骨道组患者健侧平均喙锁关节和肩锁关节的间隙与患侧对比差异无统计学意义（P>0.05）。两组患者术后末次随访患肢疼痛均有明显减轻,术前与术后VAS评分对比差异具有统计学意义,两组组间对比差异无统计学意义。四袢双骨道组重返运动的时间较双袢单骨道组明显缩短,重返患者数目明显多于双袢单骨道组,且Constant功能评分、Karlsson肩锁关节功能评分均明显优于双袢单骨道组,差异均具有统计学意义（P<0.05）。四袢双骨道组并发症明显少于双袢单骨道组。 结论采用关节镜下双骨道四袢固定治疗Rockwood V型脱位,方法固定可靠,并发症少,较双袢单骨道固定效果更佳,是治疗急性肩锁关节Rockwood V型脱位损伤较好的方法。     

Generation of TIM3 inhibitory single-domain antibodies to boost the antitumor activity of chimeric antigen receptor T cells

Targeting inhibitory immune checkpoint molecules has significantly altered cancer treatment regimens. T cell immunoglobulin and mucin domain 3 (TIM3) is one of the major inhibitory immune checkpoints expressed on T cells. Blocking the engagement of TIM3 and its inhibitory ligand galectin-9 may potentiate the effects of immunotherapy or overcome the adaptive resistance to the therapeutic blockade of programmed cell death protein 1, cytotoxic T-lymphocyte-associated protein 4, B- and T-lymphocyte attenuator and lymphocyte-activation gene 3, amongst others, as each of these immune checkpoints harbors unique properties that set it apart from the rest. Heavy chain variable fragment (VH)-derived single-domain antibodies (sdAbs) represent a class of expanding drug candidates. These sdAbs have unique advantages, including their minimal size in the antibody class, ease of expression, broad scope for modular structure design and re-engineering, and excellent tumor penetration. In the present study, two sdAbs, TIM3-R23 and TIM3-R53, were generated by immunizing rabbits with the recombinant extracellular domain of TIM3 and applying phage display technology. These sdAbs were easily expressed in mammalian cells. The purified sdAbs were able to bind to both recombinant and cell surface TIM3, and blocked it from binding to the ligand galectin-9. In vivo studies demonstrated that TIM3-R53 was able to potentiate the antitumor activity of chimeric antigen receptor T cells that targeted mesothelin. In conclusion, the results of the present study suggested that TIM3-R53 may be a novel and attractive immune checkpoint inhibitor against TIM3, which is worthy of further investigation.     

miR-188-5p promotes oxaliplatin resistance by targeting RASA1 in colon cancer cells

The efficacy of chemotherapy for colon cancer is limited due to the development of chemoresistance. MicroRNA (miR)-188-5p is downregulated in various types of cancer. The aim of the present study was to explore the molecular role of miR-188 in oxaliplatin (OXA) resistance. An OXA-resistant colon cancer cell line, SW480/OXA, was used to examine the effects of miR-188-5p on the sensitivity of colon cancer cells to OXA. The target of miR-188-5p was identified using a luciferase assay. Cell cycle distribution was also assessed using flow cytometry. The measurement of p21 protein expression, Hoechst 33342 staining and Annexin V/propidium iodide staining was used to evaluate apoptosis. The expression of miR-188-5p significantly increased in SW480/OXA compared with wild-type SW480 cells. The luciferase assay demonstrated that miR-188-5p inhibited Ras GTPase-activating protein 1 (RASA1; also known as p120/RasGAP) luciferase activity by binding to the 3′-untranslated region of RASA1 mRNA, suggesting that miR-188-5p could target RASA1. In addition, miR-188-5p downregulation or RASA1 overexpression promoted the chemosensitivity of SW480/OXA, as evidenced by increased apoptosis and G₁/S cell cycle arrest. Moreover, RASA1 silencing abrogated the increase in cell apoptosis induced by the miR-188-5p inhibitor. The findings of the present study suggested that miR-188-5p could enhance colon cancer cell chemosensitivity by promoting the expression of RASA1.     

Blocking the short isoform of augmenter of liver regeneration inhibits proliferation of human multiple myeloma U266 cells via the MAPK/STAT3/cell cycle signaling pathway

Multiple myeloma (MM) is the second most common haematological malignancy and remains an incurable disease, with most patients relapsing and requiring further treatment. Augmenter of liver regeneration (ALR) is a vital protein affecting fundamental processes such as energy transduction, cell survival and regeneration. Silencing ALR inhibits cell proliferation and triggers apoptosis in human MM U266 cells. However, little is known about the role of 15-kDa-ALR on MM. In the present study, the role of 15-kDa-ALR in human MM cells was investigated. Blocking extracellular 15-kDa-ALR with an anti-ALR monoclonal antibody (McAb) decreased the proliferation and viability of U266 cells. However, the results of flow cytometry revealed no changes in apoptosis, and the expression levels of Bax, Bcl-2, caspase-3 and cleaved caspase-3 were not affected. However, combined treatment with anti-ALR McAb and epirubicin increased the apoptosis of U266 cells. RNA sequencing results indicated that the ERK1/2, JNK-MAPK and STAT3 signaling pathways, as well as the cell cycle, were associated with the mechanism of action of the anti-ALR McAb, and PCR, western blotting and cell cycle analysis confirmed these results. The present findings suggested that blocking extracellular 15-kDa-ALR in U266 cells with an anti-ALR McAb decreased cell proliferation via the MAPK, STAT3 and cell cycle signaling pathways without increasing apoptosis. Thus, 15-kDa-ALR may be a new therapeutic target for myeloma.     

Deciphering the structure,function, expression and regulation of aquaporin-5 in cancer evolution

In recent years, the morbidity rate resulting from numerous types of malignant tumor has increased annually, and the treatment of tumors has been attracting an increasing amount of attention. A number of recent studies have revealed that the water channel protein aquaporin-5 (AQP5) has become a major player in multiple types of cancer. AQP5 is abnormally expressed in a variety of tumor tissues or cells and has multiple effects on certain biological functions of tumors, such as regulating the proliferation, apoptosis and migration of tumor cells. It has been suggested that AQP5 may play an important role in the process of tumor development, opening up a new field of tumor research. The present review highlighted the structure of AQP5 and its role in tumor progression. Furthermore, the expression of AQP5 in different malignant neoplasms was summarized. In addition, the influence of not only drugs, but also different compounds on AQP5 were summarized. In conclusion, according to the findings in the present review, AQP5 has potential as a novel therapeutic target in human cancer, and other AQPs should be similarly investigated.