The value of ultrasound parameters in predicting the efficacy of transabdominal ultrasound-guided suction curettage alone in the treatment of cesarean scar pregnancy.

OBJECTIVE: To investigate the value of ultrasound parameters in assessing the efficacy of transabdominal ultrasound (TAUS)-guided suction curettage alone for cesarean scar pregnancy (CSP). METHODS: Secondary retrospective analysis of a prospective study consisted of 137 women diagnosed with CSP who were performed TAUS-guided suction curettage alone for the first time at Maternity and Child Health Care of Guangxi Zhuang Autonomous Region in China. Prior to surgery, an ultrasound examination was conducted. Based on the need for secondary intervention, the patients were categorized into failure group and success group, and the predictive factors for failure of TAUS-guided suction curettage alone were analyzed. RESULTS: Multivariate logistic regression showed that maximum diameter of the gestational sac>29 mm (odds ratio [OR] = 4.043, 95% CI: 1.100-14.862), residual myometrium thickness ≤1.8 mm (OR = 3.719, 95% CI: 1.148-12.048) and chorionic villi thickness at the scar >4.7 mm (OR = 15.327, 95% CI: 4.617-50.881) were independent predictors of failure in TAUS-guided suction curettage alone for CSP. Furthermore, the logistic regression model that was jointly constructed by these three predictors demonstrated an area under the curve, sensitivity, specificity, and Youden index of 0.913, 0.912, 0.864, and 0.776, respectively. CONCLUSION: The maximum diameter of the gestational sac, residual myometrium thickness, and chorionic villi thickness at the scar has certain predictive efficacy of TAUS-guided suction curettage alone for CSP. Nevertheless, it is more valuable to apply the model of this study, composed of the three ultrasound parameters, for this prediction purpose.

Identification of highly effective inhibitors against SARS-CoV-2 main protease: From virtual screening to in vitro study.

Background and Objective: The public's safety has been significantly jeopardized by the pandemic of COVID-19, which is brought on by the highly virulent and contagious SARS-CoV-2 virus. Finding novel antiviral drugs is currently of utmost importance for the treatment of patients with COVID-19. Main protease (3CLpro) of SARS-CoV-2 is involved in replication of virus, so it is considered as a promising target. Using small molecules to inhibit SARS-CoV-2-3CLpro activity may be an effective way to prevent viral replication to fight COVID-19. Despite the fact that some SARS-CoV-2-3CLpro inhibitors have been described, only few of them have high levels of inhibition at nanomolar concentrations. In this study, we aimed to screen out effective SARS-CoV-2-3CLpro inhibitors. Methods: To identify highly effective SARS-CoV-2-3CLpro inhibitors, a pharmacophore mapping and multiple-conformation docking were efficiently applied to find novel hit compounds from a database. Then, the stability of the 3CLpro-hit complexes was validated by using molecular dynamics simulation. Finally, biological assay was used to assess the inhibition effects of hit compounds on SARS-CoV-2-3CLpro. Results: Four hit compounds were identified by using computer-assisted strategy. Molecular dynamics simulation suggested that these hits bound stably to the 3CLpro-active pocket. Bioassay showed that all the hits had potent inhibition against SARS-CoV-2-3CLpro with IC50 values in the range of 0.017-0.83 µM. Particularly, hit one was the best 3CLpro inhibitor and its inhibition effect of SARS-CoV-2-3CLpro (IC50 = 0.017 ± 0.003 µM) was about 236 times stronger than that of ML300 (IC50 = 4.01 ± 0.66 µM). Conclusion: These data indicate that hit one could be regarded as an anti-SARS-CoV-2 candidate worth exploring further for the treatment of COVID-19.

Potential of Black Phosphorus in Immune-Based Therapeutic Strategies.

Black phosphorus (BP) consists of phosphorus atoms, an essential element of bone and nucleic acid, which covalently bonds to three adjacent phosphorus atoms to form a puckered bilayer structure. With its anisotropy, band gap, biodegradability, and biocompatibility properties, BP is considered promising for cancer therapy. For example, BP under irradiation can convert near-infrared (NIR) light into heat and reactive oxygen species (ROS) to damage cancer cells, called photothermal therapy (PTT) and photodynamic therapy (PDT). Compared with PTT and PDT, the novel techniques of sonodynamic therapy (SDT) and photoacoustic therapy (PAT) exhibit amplified ROS generation and precise photoacoustic-shockwaves to enhance anticancer effect when BP receives ultrasound or NIR irradiation. Based on the prospective phototherapy, BP with irradiation can cause a "double-kill" to tumor cells, involving tumor-structure damage induced by heat, ROS, and shockwaves and a subsequent anticancer immune response induced by in situ vaccines construction in tumor site, which is referred to as photoimmunotherapy (PIT). In conclusion, BP shows promise in natural antitumor biological activity, biological imaging, drug delivery, PTT/PDT/SDT/PAT/PIT, nanovaccines, nanoadjuvants, and combination immunotherapy regimens.

The Discovery of Potential MDM2 Inhibitors: A Combination of Pharmacophore Modeling, Virtual Screening, Molecular Docking Studies, and in†vitro/in†vivo Biological Evaluation.

Small-molecule inhibitors of MDM2 that block the MDM2-p53 protein-protein interaction have been considered as potential therapeutic agents for the treatment of cancer. Here, we identify five highly potent inhibitors of MDM2 (termed as WY 1-5) that display significant inhibitory effects on MDM2-p53 interaction by using a combined strategy of pharmacophore modeling, virtual screening, and molecular docking studies. Among them, WY-5 is the most active MDM2 inhibitor with an IC50 value of 14.1±2.8 nM. Moreover, WY-5 significantly up-regulate the protein level of p53 in SK-Hep-1 cells harboring wild-type p53. In vitro anticancer study reveals that WY-5 markedly inhibits the survival of SK-Hep-1 cells. In vivo anticancer study suggests that WY-5 significantly inhibits the growth of SK-Hep-1 cells-derived xenograft in nude mice, with no observable toxicity. Our results demonstrate that WY-5 may be a promising candidate for the treatment of cancer harboring wild-type p53.