Ten pyrazole derivatives were synthesized and evaluated for their ability to inhibit the replication of influenza virions. All the compounds were synthesized in good-to-excellent yield, and the structures were ascertained with the help of (1) H NMR, (13) C NMR, mass, and elemental analysis. Among the tested series, compound 4i was identified as the most potent analog against the H1N1 virus, with IC50  = 5.4 µM, while the rest of the compounds showed mild-to-moderate inhibition of infection. Moreover, these compounds showed excellent inhibitory activity against influenza A neuraminidase (NA), with IC50 values ranging from 2.15 to 7.54 µM, among which compound 4i showed the most prominent inhibition with IC50  = 1.32 µM. To further exemplify the molecular contacts with NA, a molecular docking study of 4i was conducted with the 3D crystal structure of enzyme H5N1-NA in complex. Results showed that target molecules interact in a similar fashion with oseltamivir and zanamivir by creating interatomic contacts with Trp178, Glu227, and Arg371. Moreover, in the toxicity assay with the porcine renal proximal cell line, LLC-PK1, the confocal images showed no appreciable change in morphological character at the highest tested dose.

Breast cancer is one of the most common malignancy in Chinese women. Up to 80% of patients with metastatic breast cancer develop bone metastasis resulting in local bone destruction and skeletal-related events such as pathological fracture and spinal cord compression. Skeletal-related events pose an enormous impact on patients' motor function and quality of life. Therefore, prevention of skeletal-related events is one of the treatment objectives of breast cancer bone metastasis, which often requires participation of multidisciplinary team to optimize therapeutic regimen for individual. Standard anti-tumor therapy includes chemotherapy, endocrine therapy, targeted therapy, immunotherapy, etc. Bone-modifying agents are the basic treatment after the occurrence of bone metastases in addition to anti-tumor therapy. As the disease progresses, patients may receive bone radiotherapy and orthopedic surgery. The purpose of this expert's consensus is to standardize diagnosis and treatment of breast cancer bone metastasis and improve the quality of life of patients.

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Objective To compare the clinical efficacy, location and length of the femoral tunnel, graft angle, and radiographic findings between the transtibial tunnel (TT) approach and the anteromedial (AM) approach in the setting of anterior cruciate ligament (ACL) reconstructionMethods From September 2020 to December 2021, prospectively, 86 consecutive patients who met the criteria for ACL reconstruction were prospectively included in this study. The patients were randomly divided into two groups, TT group and am group, according to the computer-generated sequence. Finally, a total of 45 patients were included in the TT group and 41 patients in the AM group. All patients were assessed for knee clinical function using the Lysholm score, International Knee Documentation Committee (IKDC) score preoperatively, 6 months postoperatively, and at last follow-up. Anteroposterior and rotational stability of the knee were assessed by the Lachman test, axial shift test, and rotarod. The location of the femoral tunnel was evaluated within 1 week postoperatively using CT three-dimensional reconstruction combined with the Bernard quadrant method. Magnetic resonance imaging (MRI) MRI of the knee was performed 1 year after surgery to assess graft tone, morphology, and signal and was graded. The angle between the graft and the joint line was measured.Results Follow up ranged from 15 to 36 months with a mean (SD) of 23.76 ± 5.63. Both procedures resulted in satisfactory clinical outcomes after ACL reconstruction, and no patients in either group developed intra-articular infection, graft fracture, and joint stiffness during follow-up. At the last follow-up, the Lysholm, IKDC, Lachman and pivot shift tests were significantly improved (P < 0.05) compared to their preoperative values in both groups, and there was no significant difference between them (P > 0.05). The JGS and JGC angles in the TT group were significantly larger than those in the AM group (P < 0.05). CT three-dimensional reconstruction showed that the femoral tunnel center position of the AM approach was lower and deeper than that of the TT approach, and the difference was statistically significant (P < 0.05). Graft MRI grade after TT approach was superior to am approach (P < 0.05).Conclusion There were no significant differences between the AM approach and the TT approach in terms of knee clinical function and stability, but the femoral tunnels of the AM approach were located deeper and lower, and closer to the femoral anatomic foot print area of the anterior cruciate ligament. The TT approach was superior to the AM approach in postoperative radiographic grading of grafts.