[Comparison of open reduction hollow nail anchoring system with loop plate fixation under arthroscopy for the treatment of posterior cruciate ligament avulsion fractures].

OBJECTIVE: To compare clinical effect between open reduction and fixation with cannulated screw and threaded rivet via posteromedial approach versus arthroscopic Endobutton plate fixation in treating posterior cruciate ligament avulsion fractures. METHODS: Clinical data of 38 patients with posterior cruciate ligament avulsion fractures from July 2020 to December 2021 were analyzed retrospectively, and divided into open reduction and internal fixation group (posterior medial approach hollow anchor system fixation) and arthroscopic fixation group (Endobutton with loop plate fixation under arthroscopy). There were 20 patients in open reduction and internal fixation group, including 16 males and 4 females, aged from 26 to 74 years old with an average of (42.9±18.8) years old;13 patients on the left side and 7 patients on the right side;12 patients were classified to typeⅡand 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;14 patients were gradeⅡand 6 patients were grade Ⅲ in back drawer test. There were 18 patients in arthroscopic fixation group, including 11 males and 7 females;aged from 24 to 70 years old with an average of (53.5±13.4) years old;11 patients on the left side and 7 patients on the right side;10 patients were classified to typeⅡand 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;11 patients were gradeⅡand 7 patients were grade Ⅲ in back drawer test. Operation time, blood loss, and quality of immediate reduction were compared between two groups. Knee range of motion, knee back drawer test, and International Knee Documentation Committee(IKDC) grading, KT2000 stability evaluation and Lysholm function score of knee joint were compared at 6 months after operation. RESULTS: All patients were followed up for 8 to 16 months with an average of (12.3±1.9) months. There were no complications such as incision infection, fracture malunion or non-union, and internal fixation loosening occurred. The avulsion fractures of knee joint were reached to imaging healing standard at 6 months after operation. Operation time and blood loss in open reduction and internal fixation group were (56.4±7.1) min and (63.2±10.2) ml, while (89.9±7.4) min and (27.7±8.7) ml in arthroscopic fixation group, respectively, and had significant difference between two groups (P<0.05). There were no differences in immediate reduction quality (χ2=0.257, P=0.612), knee joint range of motion at 6 months after opertaion (t=0.492, P=0.626), knee joint rear drawer test ( χ2=0.320, P=0.572), IKDC classification of knee joint (χ2=0.127, P=0.938), KT2000 stability evaluation (χ2=0.070, P=0.791), and knee Lysholm function score (t=0.092, P=0.282) between two groups. CONCLUSION: Posterior medial approach with hollow anchoring system fixation and arthroscopic Endobutton with loop plate fixation for the treatment of posterior cruciate ligament tibial occlusion avulsion fracture could achieve satisfactory clinical results, and arthroscopic surgery has less bleeding, but also has a longer learning curve and longer operation time than traditional incision surgery. The surgeon needs to make a choice according to clinical situation of patient and their own surgical inclination.

Discovery of a Novel and Potent LCK Inhibitor for Leukemia Treatment via Deep Learning and Molecular Docking.

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.