Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Objective To compare the clinical efficacy between bone cement-augmented pedicle screw fixation and bone filling vertebroplasty for stable osteoporotic thoracolumbar burst fracture (TBF).Methods From August 2014 to August 2017,48 patients with stable osteoporotic TBF but no neurological symptoms were treated at Department of Orthopedics,The First Affiliated Hospital to Chongqing Medical University.Those undergoing bone cement-augmented pedicle screw fixation were assigned into Group A while those undergoing bone filling vertebroplasty into Group B.The clinical efficacy was evaluated by comparing visual analogue scale (VAS) for pain assessment,Oswestry disability index (ODI),compression ratio of anterior vertebral height,and cobb kyphotic angle between preoperation and postoperation.The 2 groups were compared in terms of operation time,bone cement consumption,blood loss,hospital stay and relative medical costs.Results Of the 48 patients included in this study,27 were in Group A and 21 in Group B.The 2 groups were comparable as their baseline characteristics were insignificantly different (P ＞ 0.05).At 3 days after operation,the VAS (2.8 ± 1.0) and ODI (26.0 ±3.5) scores for group B were significantly lower than those for group A (4.6 ± 1.3 and 34.3 ± 2.9) (P ＜ 0.05).In group A at 3 months after operation and final follow-up,the VAS (2.9 ±0.9 and 2.3 ±0.7) and ODI (24.7 ±3.1 and 23.1 ±4.6) scores were significantly lower than those at 3 days after operation (4.6 ± 1.3 and 34.3 ± 2.9) (P ＜ 0.05).In group B at 3 months after operation and final follow-up,the VAS (2.8 ±0.9 and 2.3 ± 1.0) and ODI (23.8 ±3.7 and 22.8 ± 5.6) scores were insignificantly better than those at 3 days after operation (2.8 ± 1.0 and 26.0 ± 3.5) (P ＞ 0.05).At 3 days and 3 months after operation and final follow-up,group B had significantly smaller compression ratios of anterior vertebral height (81.1％ ± 3.7％,81.1％ ± 3.4％ and 75.6％ ± 5.8％) than group A did (91.4％ ±4.4％,90.1％ ±2.9％ and 83.5％ ±4.4％) but significantly larger cobb kyphotic angles (17.0° ± 4.0°,18.0° ± 3.5 ° and 22.1 ° ± 3.6°) than group A (14.0° ± 3.2°,14.3° ± 5.5° and 19.2° ± 3.2°) (P ＜ 0.05).The compression ratio of anterior vertebral height and cobb kyphotic angle at the final follow-up in all the patients were significantly improved compared with those at 3 days and 3 months after operation (P ＜ 0.05).Group B had significantly less operation time (51.5 ±7.3 min),blood loss (16.0 ± 8.2 mL),hospital stay (3.4 ±0.9 d) and medical costs per person (34,000 ±4,000 RMB yuan) than group A (91.5 ± 9.8 min,77.4 ± 16.5 mL,8.7 ± 2.2 d and 55,000 ± 9,000 RMB yuan),but significantly larger bone cement consumption (5.1 ± 0.7 mL) than group A (1.9 ± 0.7 mL) (P ＜ 0.05).Conclusion For patients with stable osteoporotic TBF,both bone cement-augmented pedicle screw fixation and bone filling vertebroplasty can lead to similar clinical outcomes,but the latter may have advantages of less invasion,faster recovery and lower medical costs.

Objective: To investigate the feasibility and value of interphase fluorescence in situ hybridization (FISH) in the pathological diagnosis, differential diagnosis and therapeutic assessment of B-cell lymphomas. Methods: The cohort included 604 cases of B-cell lymphoma which were collected at West China Hospital from May 2010 to December 2016.And all were subjected to interphase FISH using 11 break apart or fusion probes (MYC, bcl-2, bcl-6, IRF4, MYC/IgH, bcl-2/IgH, CCND1/IgH, IgH, API2/MALT1, p53/ATM, and D13S319/CEP12). Results: The median age of the 604 B-cell lymphoma patients was 47.7 (aged 2-90) years including 372 men and 232 women. All the cases was divided into 463 large B cell lymphomas(LBL) and 141 small B cell lymphomas, and the total interphase FISH positive rate was 59.8% (361/604). Among the 463 LBL, 12.5% (58/463), 9.5% (44/463) and 2.2% (10/463) of cases showed MYC, bcl-6 and bcl-2 gene rearrangements respectively; and 363 diffuse large B cell lymphoma (DLBCLs) were reclassified as germinal center B-cell (GCB) subtype (38.6%, 140/363) and non-GCB subtype (61.4%, 223/363) by Hans algorithm. The rearrangement rates in GCB and non-GCB DLBCL were 45.7%(64/140)and 21.5%(48/223; P=0.001), respectively. Compared to the non-GCB DLBCL, GCB DLBCL showed higher MYC and bcl-2 gene rearrangements (P=0.001). Eleven (2.4%, 11/463) cases had MYC and bcl-6 or bcl-2 gene rearrangement (double-hit lymphoma); one (0.2%, 1/463) case had MYC, bcl-6 and bcl-2 gene rearrangements (triple-hit lymphoma); two (0.4%, 2/463) cases had bcl-2 and bcl-6 gene rearrangements. MYC translocation and MYC/IgH fusion were detected in 94.2%(81/86) and 83.7%(72/86) cases of Burkitt lymphomas. IRF4 rearrangement was detected in two cases of IRF4+ LBCL. Genetic abnormalities were detected in 9/19, 100%(29/29), 30.8%(12/39) and 68.5%(37/54) cases of follicular lymphoma, mantle cell lymphoma, MALT lymphoma and chronic lymphocytic leukemia, respectively. Conclusions Interphase FISH can rapidly and accurately detect the genetic changes in B-cell lymphomas. Different genetic changes are specifically valuable to the diagnosis, differential diagnosis, prognosis evaluation and treatment guidance of various B-cell lymphomas.