Comparing the role of different treatment modalities in locoregionally advanced olfactory neuroblastoma: The 20-year clinical experience of a single institution.

BACKGROUND: The clinical value of different treatment modalities, especially systemic chemotherapy (CT) in patients with locoregionally advanced olfactory neuroblastoma (LA ONB) remains unclear. METHODS: Patients with LA ONB from 2000 to 2020 at our center were collected retrospectively. The entire cohort was divided into combined systemic and local therapy (CSLT) versus local therapy (LT) groups (grouping method 1), and the same cohort was divided into neoadjuvant chemotherapy (NAC) versus non-NAC groups (grouping method 2). CSLT group included patients treated with CT + LT. LT group included patients treated with surgery (SG), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or any combination of the above methods. LT group was further divided into mono-modality local therapy (MOLT) group and multi-modality local therapy (MULT) group. MOLT group included patients treated with RT alone or SG alone. MULT group included patients treated with SG + RT/CCRT, or CCRT alone. NAC group included patients treated with NAC + LT ± adjuvant chemotherapy (ADC). Non-NAC group included patients who received LT ± ADC. RESULTS: A total of 111 patients with LA ONB were included. The median follow-up was 80.2 months (range, 2.1-254.9). The 5- and 10-year OS rates were 70.2% and 61.3%, respectively. In univariate analysis, patients treated with NAC (n = 43) had significantly better overall survival (OS) compared with those without NAC (n = 68) (p = 0.041). Patients in MULT group (n = 45) had significantly improved OS (p = 0.004) and PFS (p = 0.003) compared with those in MOLT group (n = 15). Multivariate analysis identified NAC and CSLT (n = 51) were independent prognostic factors for superior OS (p = 0.020, p = 0.046). CONCLUSIONS: Our study suggested that CSLT, especially a combination of NAC and LT, improved the survival of patients with LA ONB. Multiple treatment modalities yielded better PFS and OS compared to single-modality treatment.

A Prospective, Randomized, Placebo-Controlled Study Assessing the Efficacy of Chinese Herbal Medicine (Huangqi Guizhi Wuwu Decoction) in the Treatment of Albumin-Bound Paclitaxel-Induced Peripheral Neuropathy.

Objective: This study aimed to evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction (HGWD), which is composed of five crude drugs (Astragali Radix, Cinnamomi Ramulus, Paeoniae Radix Alba, Zingiberis Rhizoma Recens, and Jujubae Fructus), in the treatment of albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy (PN) in Chinese patients with breast cancer (BC). Methods: This trial was conducted at the National Cancer Center in China from January 2020 to June 2022. The eligible participants were assigned randomly in a 1:1 ratio to an HGWD group or a control group. The outcome measure was EORTC QLQ-CIPN20 questionnaire. Results: 92 patients diagnosed with BC were enrolled and randomized to either HGWD group (n = 46) or control group (n = 46). There were no significant differences in baseline characteristics between the two groups (p > 0.05). A statistical analysis of the sensory and motor functions of the EORTC QLQ-CIPN20 scores showed that patients in the HGWD group reported a larger decrease in CIPN sensory scores than those in the control group (p < 0.001). The EORTC QLQ-CIPN20 autonomic scores showed no statistical significance between the two groups (p > 0.05). Conclusions: HGWD packs could significantly improve patients' nab-PTX-induced PN, increase the tolerance for nab-PTX-containing chemotherapy, and further improve the quality of life of patients with BC.

Schaftoside inhibits 3CLpro and PLpro of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CLpro and PLpro with IC50 values of 1.73 ± 0.22 and 3.91 ± 0.19 µmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC50 of 11.83 ± 3.23 µmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

A network pharmacology-based strategy to explore the pharmacological mechanisms of Antrodia camphorata and antcin K for treating type II diabetes mellitus.

BACKGROUND: Diabetes mellitus is a chronic carbohydrate metabolism disorder, which could develop a series of complications and thus lead to poor quality of life or even mortality. Antrodia camphorata is a rare parasitic fungus and has been proven to be effective for treating type II diabetes. PURPOSE: This study aims to evaluate the anti-diabetic activities of A. camphorata and its main compound antcin K, as well as to demonstrate the mechanisms. STUDY DESIGN AND METHODS: Network pharmacology was used to explore the potential targets of 12 major compounds of A. camphorata on diabetes. The core targets were analyzed by protein-protein interactions and the key pathways were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG). The anti-diabetic effects of A. camphorata and antcin K were evaluated using a high-fat diet (HFD)-induced diabetic mice model and oral glucose tolerance test (OGTT). The mRNA expressions were assessed using qPCR. RESULTS: Network pharmacology revealed 17 core targets between the 12 compounds and diabetes. The insulin resistance and NF-κB signaling pathways were enriched using KEGG. Five insulin resistance-related targets were focused on and antcin K (1/2) was discovered in the compound-target-pathway network. In vivo studies exhibited that A. camphorata and antcin K could dose-dependently reduce blood levels of glucose and lipids, decrease serum levels of insulin and leptin, and increase serum levels of adiponectin in HFD mice (p < 0.05). The mechanism could be through modulating the expressions of Tnfα, Il6, and Pparγ. The OGTT test also showed the down-regulatory effects of A. camphorata and antcin K on blood glucose. CONCLUSION: This study demonstrates that A. camphorata and its major compound antcin K possess potent anti-diabetic effects. The mechanism may be through the insulin resistance pathway.

Glabrone as a specific UGT1A9 probe substrate and its application in discovering the inhibitor glycycoumarin.

UDP-glucuronosyltransferase 1A9 (UGT1A9) is one of the most important UGT isoforms, and plays an important role in the metabolic elimination of therapeutic drugs via glucuronidation. Herbal medicines affecting the activity of UGT1A9 may influence the metabolism of related drugs, thus causing herb-drug interactions and even adverse effects. However, few methods are available to evaluate the activity of UGT1A9. In this study, a natural product glabrone was discovered as an isoform-specific probe substrate for UGT1A9. The Vmax and Km values of glabrone were 362.6 nmol/min/mg protein and 17.2 µM for human liver microsomes (HLMs), and 382.3 nmol/min/mg protein and 16.6 µM for recombinant human UGT1A9, respectively. Glabrone 7-O-glucuronide, the UGT1A9 metabolite of glabrone, was prepared by using a plant glucuronosyltransferase UGT88D1, and the structure was identified by NMR spectroscopy. Using glabrone as a probe, we established a rapid HPLC method to screen UGT1A9 inhibitors from 54 natural products isolated from the Chinese herbal medicine licorice. Among them, glycycoumarin was found as a potent UGT1A9 inhibitor with an IC50 value of 6.04 µM. In rats, the pretreatment of glycycoumarin (4 mg/kg, i.p.) for 3 days could remarkably increase the plasma concentrations of dapagliflozin while decrease the concentrations of dapagliflozin-O-glucuronide after administration of dapagliflozin (1 mg/kg, i.v.), which is mainly metabolized by UGT1A9. The results indicated the potential risk of herb-drug interactions between licorice and UGT1A9-metabolizing drugs.