Standard versus customised locking plates for fixation of schatzker ii tibial plateau fractures

Aim3D-printed implants could improve the capture of fracture fragments for improved stability of tibial plateau fracture fixation. The aim of this study was to compare the biomechanical strength of fixation constructs using standard and customised 3D-printed proximal tibial locking plates for fixation of tibial plateau fractures.MethodsThis is a biomechanical study utilising six pairs of cadaveric tibiae. Fractures were created in an identical fashion using an osteotome and mallet, and fixed using either a standard, commercially-available proximal tibia locking plate or a customised 3D-printed plate. Design and production of the customised plates followed a “3D printing at point-of-care” model. Customised stainless steel 316 L plates were produced within a local additive manufacturing laboratory based upon pre-operative CT scans. Determination of implant choice within each cadaver pair was performed via simple randomisation. Following fracture fixation, the tibiae were skeletalised and biomechanically tested using a customised loading jig and a size-matched femoral knee prosthesis. The constructs were loaded cyclically from 100 N to approximately three times the cadaveric body-weight at 5 Hz for 10 000 cycles. Every 1000 cycles, the test was paused and the tibia was physically checked for failure. If failure had not occurred by the end of the testing cycle, the construct was loaded to failure and the load at which the construct failed was noted.ResultsFixation constructs using the 3D-printed plates performed comparably to those using the standard plates. There was no significant difference in the degree of fracture fragment displacement in both constructs. Overall longitudinal construct stiffness and load to failure was higher in the 3D-plates group but this did not reach statistical significance.ConclusionProduction of customised plates for proximal tibia fractures at point-of-care is feasible, however fixation constructs with these plates did not provide any biomechanical advantage over standard plates in terms of axial loading stiffness.     

Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44+ cancer stem cells

Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation.Here, we report the identification and separation of CD44⁺ cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44^± cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24 h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry.Low concentration of ATRA (1 μM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44^± cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1.We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma.     

Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study

Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation.

Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes.

Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark).

Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC₅₀ value of 13.8?mg/mL on PLA₂ from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC₅₀ value of 16.6?mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC₅₀ value of 0.92?mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of??128.96 compared to standard phenidone (?103.61). Thus, the current study validates the application of WS for inflammatory diseases.

Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases.     

PD-L1高表达晚期非小细胞肺癌患者单纯免疫治疗与免疫联合化疗疗效比较

背景与目的以免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）为代表的免疫治疗越来越广泛地应用于肺癌治疗。然而，对于程序性死亡受体配体1（programmed cell death-ligand 1, PD-L1）高表达，即肿瘤比例评分（tumor proportion score, TPS）≥50%的晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者，采用单纯免疫治疗还是免疫联合化疗在临床上仍存争议。本研究旨在评估PD-L1高表达的晚期NSCLC患者接受单纯免疫治疗与免疫联合化疗的疗效。方法本研究回顾性分析了49例PD-L1高表达晚期NSCLC患者的临床资料。PD-L1表达采用22C3抗体行免疫组化染色，按TPS判读PD-L1表达水平。比较不同临床特征分组患者的客观缓解率（objective response rate，ORR）和无进展生存时间（progression free survival, PFS）。结果免疫单药与免疫联合化疗组的ORR分别为47.1%（8/17）和43.8%（14/32），差异无统计学意义（P=0.825）。免疫单药与免疫联合化疗组的中位PFS分别为8.0个月和6.8个月，差异无统计学意义（P=0.502）。并对本组PD-L1高表达患者免疫治疗的预测因素进行了分析，结果显示，一线免疫治疗ORR（12/19, 63.2%）显著优于二线及以上免疫治疗（10/30, 33.3%），差异有统计学意义（P=0.041），二者间PFS无差异。年龄、性别、吸烟史、功能状态评分（performance status, PS）、病理类型、肿瘤大小、肿瘤淋巴结转移（tumor node metastasis, TNM）分期与ORR和PFS不相关。结论PD-L1高表达的晚期NSCLC患者接受免疫单药和免疫联合化疗的疗效相近。PD-L1高表达患者一线免疫治疗的ORR更佳。对此类人群的最佳治疗方案有待于前瞻性临床研究进一步探索。     

骨填充网袋椎体成形术与经皮椎体后凸成形术治疗Kümmell病的疗效比较

目的比较骨填充网袋椎体成形术（Vesselplasty）与经皮椎体后凸成形术（percutaneous kyphoplasty，PKP）治疗 Kümmell 病的临床疗效。方法2015 年 1 月—2018 年 12 月收治 63 例 Kümmell 病患者，其中 28 例采用 Vesselplasty 治疗（Vesselplasty 组），35 例采用 PKP 治疗（PKP 组）。两组患者性别、年龄、病程、骨密度 T 值、骨折节段及术前疼痛视觉模拟评分（VAS）、Oswestry 功能障碍指数（ODI）、伤椎前缘高度、后凸 Cobb 角等一般资料比较，差异均无统计学意义（P>0.05），具有可比性。记录两组手术时间、术中透视时间、骨水泥注射量、骨水泥渗漏率、骨水泥弥散面积率和随访期间并发症发生情况，以及术前、术后 1 d、末次随访时 VAS 评分、ODI、伤椎前缘高度、后凸 Cobb 角。 结果两组患者均获随访，随访时间 12～36 个月，平均 24.2 个月。Vesselplasty 组手术时间、术中透视时间、骨水泥注射量、骨水泥弥散面积率均明显小于 PKP 组（P<0.05）。Vesselplasty 组骨水泥渗漏率（7.14%）明显低于 PKP 组（34.29%）（χ²=5.153，P=0.023）。两组患者术后 1 d 及末次随访时 VAS 评分、ODI、伤椎前缘高度、后凸 Cobb 角均较术前显著改善（P<0.05），术后两组间比较差异均无统计学意义（P>0.05）。随访期间两组均未见术椎再塌陷，Vesselplasty 组邻椎骨折发生率（7.14%）与 PKP 组（14.29%）比较，差异无统计学意义（χ²=0.243，P=0.622）。 结论Vesselplasty 和 PKP 治疗 Kümmell 病疗效相似，均能有效缓解患者疼痛症状，改善生活质量，部分恢复伤椎高度，矫正椎体后凸。但前者具有手术时间短、术中透视时间少、骨水泥渗漏少等优势。     

"管氏培元九宫"针法治疗功能性阳痿疗效观察

目的观察"管氏培元九宫"针法治疗功能性阳痿的临床疗效。方法将60例功能性阳痿患者按随机数字表法随机分为治疗组和对照组,每组30例。治疗组采用"管氏培元九宫"穴,按"洛书九宫数"施行针刺治疗;对照组口服复方玄驹胶囊。观察两组治疗前后国际勃起功能指数-5(IIEF-5)评分,并比较临床疗效。结果治疗组总有效率为80.0%,对照组为70.0%,两组比较差异具有统计学意义(P<0.05)。治疗组治疗后IIEF-5评分高于治疗前和对照组(P<0.05)。结论"管氏培元九宫"针法对功能性阳痿具有较好临床疗效。     

Generalized,severe epidermolysis bullosa simplex caused by a Keratin 5 p.E477K mutation

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease.     

miR-513a-5p慢病毒载体的构建及其对人骨肉瘤细胞放疗敏感性的影响

目的:构建miR-513a-5p慢病毒过表达载体，转染人骨肉瘤细胞株，观察miR-513a-5p对人骨肉瘤细胞放疗敏感性的影响。方法:PCR法扩增人miR-513a-5p基因，克隆入pLentis-CMV-GFP-MCS-PGK-PURO载体获得重组质粒pLentis-miR513a，双酶切鉴定并测序后将正确的重组质粒和对照质粒转染293FT细胞制备慢病毒，分别转染骨肉瘤HOS和U2OS细胞，qRT-PCR法及荧光显微镜鉴定转染结果。克隆形成实验、MTT法检测miR-513a-5p高表达HOS和U2OS细胞在X射线照射下细胞存活情况。结果:双酶切及测序结果确定成功构建miR-513a-5p慢病毒载体pLentis-miR513a。qRT-PCR结果提示，转染骨肉瘤细胞株后miR-513a-5p表达显著升高。克隆形成实验结果显示miR-513a-5p高表达后骨肉瘤细胞在X射线照射下细胞增殖减慢。MTT结果提示miR-513a-5p高表达骨肉瘤细胞经X射线照射后细胞存活减少。结论:成功构建了miR-513a-5p慢病毒载体，建立了高效稳定表达miR-513a-5p的骨肉瘤细胞株，高表达miR-513a-5p能显著增加X射线照射后骨肉瘤细胞的放疗敏感性。