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Background: At present, the optimal treatment for posterior cruciate ligament tibial avulsion fracture (PCLTAF) combined with concomitant ipsilateral lower limb fractures remains unclear. The present study aimed to assess the preliminary outcomes of treatment for PCLTAF with concomitant ipsilateral lower limb fractures by open reduction and internal fixation (ORIF)., Materials and Methods: The medical records of patients who sustained PCLTAF with concomitant ipsilateral lower limb fractures between March 2015 and February 2019 and underwent treatment at a single institution were retrospectively reviewed. Imaging examinations performed at the time of injury were applied to identify concomitant ipsilateral lower limb fractures. We used 1:2 matching between patients with PCLTAF combined with concomitant ipsilateral lower limb fractures (combined group; n = 11) and those with isolated PCLTAF (isolated group; n = 22). Outcome data were collected, including the range of motion (ROM) and visual analogue scale (VAS), Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores. At the final follow-up, the clinical outcomes were compared between the combined and isolated groups and between patients who underwent early-stage surgery and those who underwent delayed treatment for PCLTAF., Results: Thirty-three patients (26 males, 7 females) were included in this study, with eleven patients having PCLTAF and concomitant ipsilateral lower limb fractures and a follow-up of 3.1 to 7.4 years (average, 4.8 years). Compared to patients in the isolated group, patients in the combined group demonstrated significantly worse Lysholm scores (85.7 ± 5.8 vs. 91.5 ± 3.9, p = 0.040), Tegner scores (4.4 ± 0.9 vs. 5.4 ± 0.8, p = 0.006), and IKDC scores (83.6 ± 9.3 vs. 90.5 ± 3.0, p = 0.008). Inferior outcomes were found in patients with delayed treatment., Conclusions: Inferior results were found in patients with concomitant ipsilateral lower limb fractures, while better outcomes were obtained in patients with PCLTAF through early-stage ORIF using the posteromedial approach. The present findings may help determine the prognoses of patients with PCLTAF combined with concomitant ipsilateral lower limb fractures treated through early-stage ORIF., (© 2023. The Author(s).)

Mesenchymal stromal cells (MSCs) are a heterogeneous population of cells that possess multilineage differentiation potential and extensive immunomodulatory properties. In mice and rats, MSCs produce nitric oxide (NO), as immunomodulatory effector molecule that exerts an antiproliferative effect on T cells, while the role of NO in differentiation was less clear. Here, we investigated the role of NO synthase 2 (NOS2) on adipogenic and osteogenic differentiation of rat MSCs. MSCs isolated from NOS2-null (NOS2 -/- ) and wild type (WT) Sprague-Dawley (SD) rats exhibited homogenous fibroblast-like morphology and characteristic phenotypes. However, after induction, adipogenic differentiation was found significantly promoted in NOS2 -/- MSCs compared to WT MSCs, but not in osteogenic differentiation. Accordingly, qRT-PCR revealed that the adipogenesis-related genes PPAR-γ, C/EBP-α, LPL and FABP4 were markedly upregulated in NOS2 -/- MSCs, but not for osteogenic transcription factors or marker genes. Further investigations revealed that the significant enhancement of adipogenic differentiation in NOS2 -/- MSCs was due to overactivation of the STAT3 signaling pathway. Both AG490 and S3I-201, small molecule inhibitors that selectively inhibit STAT3 activation, reversed this adipogenic effect. Furthermore, after high-fat diet (HFD) feeding, knockout of NOS2 in rat MSCs resulted in significant obesity. In summary, NOS2 is involved in the regulation of rat MSC adipogenic differentiation via the STAT3 signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qin, Chen, Wang, Huang, Zhang, Liang, Du, Lai, Ding, Yu and Xiang.)

Backgrounds: Surgical resection and adjunct chemotherapy or radio-therapy has been applied for the therapy of superficial malignant tumor in clinics. Whereas, there are still some problems limit its clinical use, such as severe pains and side effect. Thus, it is urgent need to develop effective, minimally invasive and low toxicity therapy stagey for superficial malignant tumor. Topical drug administration such as microneedle patches shows the advantages of reduced systemic toxicity and nimble application and, as a result, a great potential to treat superficial tumors., Methods: In this study, microneedle (MN) patches were fabricated to deliver photosensitizer IR820 and chemotherapy agent cisplatin (CDDP) for synergistic chemo-photodynamic therapy against breast cancer., Results: The MN could be completely inserted into the skin and the compounds carrying tips could be embedded within the target issue for locoregional cancer treatment. The photodynamic therapeutic effects can be precisely controlled and switched on and off on demand simply by adjusting laser. The used base material vinylpyrrolidone-vinyl acetate copolymer (PVPVA) is soluble in both ethanol and water, facilitating the load of both water-soluble and water-insoluble drugs., Conclusions: Thus, the developed MN patch offers an effective, user-friendly, controllable and low-toxicity option for patients requiring long-term and repeated cancer treatments.

Solid dispersion is a widely used method to improve the dissolution and oral bioavailability of water-insoluble drugs. However, due to the strong hydrophobicity, the drug crystallization in the release media after drug dissolution and the resulted decreased drug absorption retards the use of solid dispersions. It is widely known that the amphiphilic copolymer can encapsulate the hydrophobic compounds and help form stable nano-dispersions in water. Inspired by this, we tried to formulate the solid dispersion of nimodipine by using amphipathic copolymer as one of the carriers. Concerning the solid dispersions, there are many important points involved in these formulations, such as the miscibility between the drug and the carriers, the storage stability of solid dispersions, the dissolution enhancement and so on. In this study, a systemic method is proposed. In details, the supersaturation test and the glass transition temperature (T g ) measurement to predict the crystallization inhibition, the ratios of different components and the storage stability, the interactions among the components were investigated in detail by nuclear magnetic resonance ( 1 H NMR) and isothermal titration calorimetry (ITC) and, the final dissolution and oral bioavailability enhancement. It was found that the amphiphilic copolymer used in the solid dispersion encouraged the formation the drug loading micelles in the release media and, finally, the problem of drug crystallization in the dissolution process was successfully solved., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)