Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for 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 (3CL^pro) and papain-like protease (PL^pro) 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 3CL^pro and PL^pro 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 3CL^pro, and K157, E167 and A246 of PL^pro. 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.

Objective:To investigate the expression of syndecan-1 (SDC1) in human venous malformations and the effect of syndecan-1 (SDC1) silences on migration, invasion and angiogenesis of human umbilical vein endothelial cells (HUVECs).Methods:Pathological samples of venous malformation were selected from 20 patients with hemangioma surgically resected in the Third Affiliated Hospital of Zhengzhou University from December 2020 to June 2021 (10 males and 10 females, aged 1-57 years, median age 7 years ). HUVECs was purchased from American Type Culture Collection (ATCC ). Immunohistochemistry was used to detect the expression of SDC1 in venous malformations. The cytological experiments of HUVECs cultured in vitro were divided into two groups, transfected SDC1 small interfering RNA (siRNA) (si-SDC1 group) and control siRNA (control group), respectively. The siRNA with the best silencing effect was selected by real-time quantitative PCR and Western Blot method for follow-up experiments. Then the ability of HUVECs migration, invasion and angiogenesis was detected by scratch test, Transwell migration and invasion test and angiogenesis test, respectively.Results:SDC1 was positive in 13 of the 20 venous malformations and was mainly expressed in the cytoplasm of venous endothelial cells. Compared with HUVECs cells in NC group, the expression of SDC1 mRNA and protein in HUVECs cells in si-SDC1 group decreased, indicated that the synthesized siRNA targeting SDC1 could silence the expression of SDC1 , and the ability of HUVECs migration, invasion and angiogenesis were enhanced in si-SDC1 group.Conclusions:SDC1 was positively expressed in venous malformations. After silencing SDC1, the migration, invasion and tube formation ability of HUVECs were enhanced.

Objective:To investigate the expression of syndecan-1 (SDC1) in human venous malformations and the effect of SDC1 silencing on the migration, invasion and angiogenesis abilities of human umbilical vein endothelial cells (HUVECs).Methods:Twenty surgically resected samples of venous malformation were collected from 20 patients with hemangioma at the Third Affiliated Hospital of Zhengzhou University from December 2020 to June 2021 (10 males and 10 females, aged 1-57 years, median age 7 years). HUVECs were purchased from American Type Culture Collection (ATCC). Immunohistochemistry staining was used to detect the expression of SDC1 in venous malformations. HUVECs cultured in vitro were divided into two groups, and were transfected with SDC1 small interfering RNA (siRNA) (si-SDC1 group) or control siRNA (control group), respectively. The siRNA with the best silencing effect was screened and tested by real-time quantitative PCR and Western blotting for follow-up experiments. The migration, invasion and angiogenesis abilities of HUVECs were measured by scratch test, Transwell migration and invasion test, and angiogenesis test, respectively. Results:(1) SDC1 was positive in 13(65.0%) of the 20 venous malformations and was mainly expressed in the cytoplasm of venous endothelial cells. (2) Compared with HUVECs in the control group, the expression of SDC1 mRNA and protein in HUVECs cells in si-SDC1 group both decreased ( P<0.05), indicating the synthesized siRNA targeting SDC1 could silence the expression of SDC1. (3) The migration, invasion and angiogenesis abilities of HUVECs were enhanced in si-SDC1 group( P<0.05). Conclusions:SDC1 was expressed in most venous malformations. After silencing SDC1, the migration, invasion and tube formation abilities of HUVECs were enhanced.

Objective:To explore the application effect of situational case-based learning (CBL) teaching method in the surgical animal experiment course.Methods:The five-year clinical medicine students of the Batch 2016 teaching reform classes in Inner Mongolia Medical University were selected as the research objects. The teaching reform Class 1 was the control group, and the teaching reform Class 2 was the experimental group, with 36 students in each group. The control group adopted traditional teaching, while the experimental group introduced situational CBL teaching. The mid-term assessment of the course was carried out, using a multi-station examination including theory and skill operation. At the same time, a questionnaire survey of course satisfaction was carried out among the two groups of students. SPSS 22.0 was used for t-test and Chi-square test. Results:The theoretical performance of the experimental group (72.44 ±7.91) was significantly higher than that of the control group (60.49±8.23), and the performance of skill operation (77.69±7.13) was significantly higher than that of the control group (60.58±8.91). The course satisfaction of the experimental group was significantly higher than that of the control group.Conclusion:The introduction of situational CBL teaching could significantly improve the classroom teaching effect of surgical animal experiments, and be beneficial for medical students to master the basic skills of surgery and the related general theory knowledge of clinical medicine.

Objective:To investigate the effect of irradiation on the expression of miR-150-5p and miR-23a-3p in human peripheral blood serum by collecting peripheral blood of tumor patients before and after radiotherapy, so as to provide scientific basis for finding radiation biomarkers.Methods:A total of 63 tumor patients treated with radiotherapy from October 2021 to March 2022 were enrolled in this study. The relative expression levels of miR-150-5p and miR-23a-3p in peripheral blood serum in these patients were detected using the real-time fluorescence quantitative PCR (qPCR) before and after radiotherapy. The differential changes in the expression levels of the two miRNAs in the peripheral blood serum of the patients before and after radiotherapy were compared, and their relationships with factors such as cancer types were analyzed.Results:The relative expression levels of miR-150-5p and miR-23a-3p in peripheral blood serum of the patients after radiotherapy were significantly lower than those before radiotherapy ( t = 4.97, Z = -2.77, P < 0.05). Among different cancer types, the relative expression level of miR-150-5p in the patients with breast cancer, esophageal cancer, or other digestive tract cancer decreased after radiotherapy ( t = 3.47, 2.47, 2.87, P < 0.05), and the relative expression level of miR-23a-3p in the patients with digestive tract cancer decreased after radiotherapy ( Z = -1.99, P < 0.05). The changes in the expression level of miR-150-5p before and after radiotherapy were not affected by gender, age, chemotherapy, and cancer type ( P > 0.05). By contrast, the changes in the expression level of miR-23a-3p before and after radiotherapy were significantly affected by gender, age, and chemotherapy ( t=2.04, -3.34, -2.29, P<0.05). Conclusions:The expression of miR-150-5p in the serum of tumor patients may be affected by radiotherapy, which has the potential to be used as a biological indicator of radiation.

Objective:To investigate the expression of syndecan-1 (SDC1) in human venous malformations and the effect of syndecan-1 (SDC1) silences on migration, invasion and angiogenesis of human umbilical vein endothelial cells (HUVECs).Methods:Pathological samples of venous malformation were selected from 20 patients with hemangioma surgically resected in the Third Affiliated Hospital of Zhengzhou University from December 2020 to June 2021 (10 males and 10 females, aged 1-57 years, median age 7 years ). HUVECs was purchased from American Type Culture Collection (ATCC ). Immunohistochemistry was used to detect the expression of SDC1 in venous malformations. The cytological experiments of HUVECs cultured in vitro were divided into two groups, transfected SDC1 small interfering RNA (siRNA) (si-SDC1 group) and control siRNA (control group), respectively. The siRNA with the best silencing effect was selected by real-time quantitative PCR and Western Blot method for follow-up experiments. Then the ability of HUVECs migration, invasion and angiogenesis was detected by scratch test, Transwell migration and invasion test and angiogenesis test, respectively.Results:SDC1 was positive in 13 of the 20 venous malformations and was mainly expressed in the cytoplasm of venous endothelial cells. Compared with HUVECs cells in NC group, the expression of SDC1 mRNA and protein in HUVECs cells in si-SDC1 group decreased, indicated that the synthesized siRNA targeting SDC1 could silence the expression of SDC1 , and the ability of HUVECs migration, invasion and angiogenesis were enhanced in si-SDC1 group.Conclusions:SDC1 was positively expressed in venous malformations. After silencing SDC1, the migration, invasion and tube formation ability of HUVECs were enhanced.

Objective:To investigate the expression of syndecan-1 (SDC1) in human venous malformations and the effect of SDC1 silencing on the migration, invasion and angiogenesis abilities of human umbilical vein endothelial cells (HUVECs).Methods:Twenty surgically resected samples of venous malformation were collected from 20 patients with hemangioma at the Third Affiliated Hospital of Zhengzhou University from December 2020 to June 2021 (10 males and 10 females, aged 1-57 years, median age 7 years). HUVECs were purchased from American Type Culture Collection (ATCC). Immunohistochemistry staining was used to detect the expression of SDC1 in venous malformations. HUVECs cultured in vitro were divided into two groups, and were transfected with SDC1 small interfering RNA (siRNA) (si-SDC1 group) or control siRNA (control group), respectively. The siRNA with the best silencing effect was screened and tested by real-time quantitative PCR and Western blotting for follow-up experiments. The migration, invasion and angiogenesis abilities of HUVECs were measured by scratch test, Transwell migration and invasion test, and angiogenesis test, respectively. Results:(1) SDC1 was positive in 13(65.0%) of the 20 venous malformations and was mainly expressed in the cytoplasm of venous endothelial cells. (2) Compared with HUVECs in the control group, the expression of SDC1 mRNA and protein in HUVECs cells in si-SDC1 group both decreased ( P<0.05), indicating the synthesized siRNA targeting SDC1 could silence the expression of SDC1. (3) The migration, invasion and angiogenesis abilities of HUVECs were enhanced in si-SDC1 group( P<0.05). Conclusions:SDC1 was expressed in most venous malformations. After silencing SDC1, the migration, invasion and tube formation abilities of HUVECs were enhanced.

Objective:To evaluate the therapeutic effect of radiofrequency ablation in the treatment of severe hemangioma with thrombocytopenia and coagulation abnormality (Kasabach-Merritt phenomenon, KMP).Methods:From April 2018 to April 2021, 11 cases of KMP in our department were retrospectively analyzed. The patients underwent MRI, color ultrasound and hematology examination. Radiofrequency ablation was performed for all patients under general anesthesia. The comprehensive, multi-level and multi-point ablation was accurately implemented under the whole-process intraoperative monitoring of color ultrasound. Postoperative ice pad was applied for the treatment area, and dressing change was carried out every day.Results:All 11 cases of KMP were treated with radiofrequency ablation, including 5 males and 6 females, aged 1 d to 2 months, with a median age of 15 d. Intraoperative color Doppler ultrasound monitoring showed that the tumor was completely ablated in the single operation. All patients were followed up for 0.5 to 2 years. The tumor was cured without recurrence. The local function was unaffected. The local scar formation was mild and the appearance was satisfactory.Conclusions:Radiofrequency ablation has great clinical value in the treatment of KMP. It makes up the shortcomings and avoids the disadvantages of traditional surgery and other conservative treatment methods. Good clinical results can be achieved by radiofrequence ablation with satifactory function and appearance.

Objective:To investigate the outcomes of therapeutic radiofrequency ablation (RFA) in unilateral intra-articular venous malformations (IAVMs) of the knee.Methods:The clinical data of 15 patients with intravascular venous malformation in the Third Affiliated Hospital of Zhengzhou University from February 2018 to May 2019 were retrospectively analyzed. There were 7 males and 8 females with an average age of 16 years (range, 5—25 years). All patients had unilateral knee involvement, ranging from localized lesions to diffuse extensive lesions. The radiofrequency ablation electrode needle with a diameter of 0.5 mm was selected and the power was adjusted to 25 W. Under the guidance of color ultrasound monitoring, the whole operation was carried out. The RFA electrode needle was inserted into the deepest site of the lesion and extracted by 1-mm graded movements until a point 1 mm from the surface of the lesion. Each ablation point was ablated for 10 to 30 seconds and multi-point ablation was done until the lesions were completely eliminated. Patients were followed up for 6 months to 1 year. Treatment outcomes were evaluated by functional activity, including extension, flexion, abduction, and adduction at the knee joint, and MRI findings, including intensity, shape, boundary, and degree of aggressiveness in the intra- and extraarticular cavities.Results:Included 15 patients; 12 had VMs in the knee joint cavity, and 3 had VMs involving both the intraarticular and extraarticular cavities (1 from the joint cavity to the calf, 1 from the joint cavity to the lower femur, and 1 from the intraarticular to the extraarticular cavity). All subjects underwent RFA, and the lesions were completely ablated and eradicated in a single operation. No recurrence was reported in the 6 months to 1 year follow-up. The knee joint remained symmetrical with the contralateral knee joint, without scarring, after the RFA.Conclusions:Radiofrequency ablation for the treatment of intra-articular venous malformation of the knee joint is a valuable minimally invasive surgical method with complete ablation, no complications, good prognosis and aesthetic appearance.