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The interference screw is a widely used fixation device in the anterior cruciate ligament (ACL) reconstruction surgeries. Despite the generally satisfactory results, problems of using interference screws were reported. By using additive manufacturing (AM) technology, we developed an innovative titanium alloy (Ti6Al4V) interference screw with rough surface and inter‐connected porous structure designs to improve the bone‐tendon fixation. An innovative Ti6Al4V interference screws were manufactured by AM technology. In vitro mechanical tests were performed to validate its mechanical properties. Twenty‐seven New Zealand white rabbits were randomly divided into control and AM screw groups for biomechanical analyses and histological analysis at 4, 8, and 12 weeks postoperatively; while micro‐CT analysis was performed at 12 weeks postoperatively. The biomechanical tests showed that the ultimate failure load in the AM interference screw group was significantly higher than that in the control group at all tested periods. These results were also compatible with the findings of micro‐CT and histological analyses. In micro‐CT analysis, the bone‐screw gap was larger in the control group; while for the additive manufactured screw, the screw and bone growth was in close contact. In histological study, the bone‐screw gaps were wider in the control group and were almost invisible in the AM screw group. The innovative AM interference screws with surface roughness and inter‐connected porous architectures demonstrated better bone‐tendon‐implant integration, and resulted in stronger biomechanical characteristics when compared to traditional screws. These advantages can be transferred to future interference screw designs to improve their clinical performance. The AM interference screw could improve graft fixation and eventually result in better biomechanical performance of the bone‐tendon‐screw construct. The innovative AM interference screws can be transferred to future interference screw designs to improve the performance of implants. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2633–2640, 2018. By using additive manufacturing (AM) technology, we developed an innovative titanium alloy (Ti6Al4V) interference screw with rough surface and inter‐connected porous structure designs to improve thebone–tendon fixation in the anterior cruciate ligament (ACL) reconstruction surgeries. Our results showed that the AM interference screw could improve graft fixation and eventually result in better biomechanical performance of the bone‐tendon‐screw construct. The innovative AM interference screws can be transferred to future interference screw designs to improve the performance of implants. [ABSTRACT FROM AUTHOR]

Ashuman beings live longer, age-related diseases such as osteoporosiswill become more prevalent. Intolerant side effects and poor responsesto current treatments are observed. Therefore, novel effective therapeuticagents are greatly needed. Here, pyrazole derivatives were designedand synthesized, and their osteoclastogenesis inhibitory effects both in vitroand in vivowere evaluated. Themost promising compound 13with a 2-(dimethylamino)ethylgroup inhibited markedly in vitroosteoclastogenesisas well as the bone resorption activity of osteoclasts. Compound 13affected osteoclast’s early proliferation and differentiationmore than later fusion and maturation stages. In ovariectomized (OVX)mice, compound 13can inhibit the loss of trabecularbone volume, trabecular bone number, and trabecular thickness. Moreover,compound 13can antagonize OVX-induced reduction of serumbone resorption marker and then compensatory increase of the boneformation marker. To sum up, compound 13has high potentialto be developed into a novel therapeutic agent for treating osteoporosisin the future. [ABSTRACT FROM AUTHOR]

Purpose: The high 5-year disease relapse rate in patients with stage I lung adenocarcinoma indicates the need for additional risk stratification parameters. This study assessed whether gene signatures translate into a pathologic feature for better disease stratification., Materials and Methods: The mutual interdependence and risk stratification power of three gene signatures, cell cycle, hypoxia, and mammalian target of rapamycin (mTOR), were investigated in nine cohorts of patients with lung adenocarcinoma and five cohorts of patients with lung squamous cell carcinoma. The translation from gene signatures to a pathologic feature, tumor necrosis, was validated in The Cancer Genome Atlas lung adenocarcinoma cohort. The translation of signature score to pathway activity was further investigated by integrative analyses using The Cancer Genome Atlas and The Cancer Protein Atlas lung adenocarcinoma data sets., Results: The results showed that the three gene signatures were mutually interdependent in lung adenocarcinoma but not in lung squamous cell carcinoma. The signature activities were higher in necrosis-positive tumors than in necrosis-negative tumors. The signature score correlated with the expression level of the representative protein that implicated the activity of each pathway. These signatures stratified patients with operable and stage I lung adenocarcinomas into different risk groups independent of age and stage. Furthermore, the signatures translated to a pathologic feature, tumor necrosis, which predicted shorter overall and relapse-free survival in patients with operable and stage I lung adenocarcinomas., Conclusion: This study showed that gene signatures could translate into a pathologic feature, tumor necrosis, with risk stratification ability in patients with operable and stage I lung adenocarcinomas.

The blood-brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers.