The Influence of Online and Offline Mixed Teaching Mode Based on TPACK on the Theoretical Knowledge and Comprehensive Ability Level of Tumor Gynecology Postgraduates.

Aim: To explore the influence of online and offline mixed teaching modes based on TPACK on theoretical knowledge and comprehensive ability of tumor gynecology postgraduates. Methods: In this study, a prospective randomized controlled study model was used to select 60 masters of oncology and gynecology who were interned in the Affiliated Hospital of the First Affiliated Hospital of Bengbu Medical College from September 2019 to April 2022 as the research objects. They were divided into a study group and a control group by random number table, with 30 cases in each group. The control group adopted the traditional teaching mode, while the study group adopted the mixed online and offline teaching mode based on TPACK to implement the teaching. The knowledge mastery, problem analysis ability and total ability of the two groups were compared before and after the practice. Results: After the practice, the scores of theoretical knowledge, clinical operation skills and case analysis ability of both groups were improved compared with those before the practice, and the scores of the study group were higher than those of the control group (P < .05). After practice, the scores of problem analysis and clinical work competence in both groups were significantly higher than those before practice, and the study group was higher than the control group (P < .05). After practice, the scores of professional technical knowledge, doctor-patient communication ability, clinical operation skill, disease observation ability and clinical first-aid ability of both groups were improved compared with those before practice, and the scores of the study group were higher than those of the control group (P < .05). Conclusion: In clinical teaching, the online and offline mixed teaching mode based on TPACK has obvious effects on improving the theoretical and clinical operation level of tumor gynecology postgraduates and the total ability of medical staff.

The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81.

A single-nucleotide polymorphism (SNP) rs12252-C of interferon-induced transmembrane protein 3 (IFITM3), resulting in a truncated IFITM3 protein lacking 21 N-terminus amino acids, is associated with severe influenza infection in the Chinese population. However, the effect of IFITM3 rs12252-C on influenza vaccination and the underlying mechanism is poorly understood. Here, we constructed a mouse model with a deletion of 21 amino acids at the N-terminus (NΔ21) of IFITM3 and then compared the antibody response between Quadrivalent influenza vaccine (QIV) immunized wild-type (WT) mice and NΔ21 mice. Significantly higher levels of haemagglutination inhibition (HI) titre, neutralizing antibodies (NAb), and immunoglobulin G (IgG) to H1N1, H3N2, B/Victory, and B/Yamagata viruses were observed in NΔ21 mice compared to WT mice. Correspondingly, the numbers of splenic germinal centre (GC) B cells, plasma cells, memory B cells, QIV-specific IgG+ antibody-secreting cells (ASC), and T follicular helper cells (TFH) in NΔ21 mice were higher compared with WT mice. Moreover, the 21-amino-acid deletion caused IFITM3 translocation from the endocytosis compartment to the periphery of cells, which also prevented the degradation of a co-stimulatory molecule of B cell receptor (BCR) CD81 on the cell surface. More importantly, a more interaction was observed between NΔ21 protein and CD81 compared to the interaction between IFITM3 and CD81. Overall, our study revealed a potential mechanism of NΔ21 protein enhancing humoral immune response by relocation to prevent the degradation of CD81, providing insight into SNP affecting influenza vaccination.

An injectable hydrogel based on Bi2Se3 nanosheets and hyaluronic acid for chemo-photothermal synergistic therapy.

To resolve poor accumulation caused by systemic administration, injectable and responsive hydrogels are the prospective drug delivery systems for localized tumor treatment, owning to negligible invasiveness and accurate administration. Herein, an injectable hydrogel, based on dopamine (DA) crosslinked hyaluronic acid and Bi2Se3 nanosheets (NSs) loading with doxorubicin (DOX) coated with polydopamine (Bi2Se3-DOX@PDA), was developed for synergistic chem-photothermal cancer therapy. The ultrathin functional Bi2Se3-DOX@PDA NSs could be responsive to the weak acidic condition and photothermal effect under NIR laser irradiation, achieving controlled release of DOX. Moreover, nanocomposite hydrogel based on hyaluronic acid matrix could be precisely administrated through intratumoral injection since its injectability and self-healing capacity, remaining at injected sites for at least 12 days. Furthermore, the excellent therapeutics effect of Bi2Se3-DOX@PDA nanocomposite hydrogel was demonstrated on 4 T1 xenograft tumor with outstanding injectability and negligible systemic side-effect. In short, the construction of Bi2Se3-DOX@PDA nanocomposite hydrogel paves a prospective path for local treatment of cancers.

Multifunctional Nanoparticles Codelivering Doxorubicin and Amorphous Calcium Carbonate Preloaded with Indocyanine Green for Enhanced Chemo-Photothermal Cancer Therapy.

Background: Multifunctional stimuli-responsive nanoparticles with photothermal-chemotherapy provided a powerful tool for improving the accuracy and efficiency in the treatment of malignant tumors. Methods: Herein, photosensitizer indocyanine green (ICG)-loaded amorphous calcium-carbonate (ICG@) nanoparticle was prepared by a gas diffusion reaction. Doxorubicin (DOX) and ICG@ were simultaneously encapsulated into poly(lactic-co-glycolic acid)-ss-chondroitin sulfate A (PSC) nanoparticles by a film hydration method. The obtained PSC/ICG@+DOX hybrid nanoparticles were characterized and evaluated by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). The cellular uptake and cytotoxicity of PSC/ICG@+DOX nanoparticles were analyzed by confocal laser scanning microscopy (CLSM) and MTT assay in 4T1 cells. In vivo antitumor activity of the nanoparticles was evaluated in 4T1-bearing Balb/c mice. Results: PSC/ICG@+DOX nanoparticles were nearly spherical in shape by TEM observation, and the diameter was 407 nm determined by DLS. Owing to calcium carbonate and disulfide bond linked copolymer, PSC/ICG@+DOX nanoparticles exhibited pH and reduction-sensitive drug release. Further, PSC/ICG@+DOX nanoparticles showed an effective photothermal effect under near-infrared (NIR) laser irradiation, and improved cellular uptake and cytotoxicity in breast cancer 4T1 cells. Importantly, PSC/ICG@+DOX nanoparticles demonstrated the most effective suppression of tumor growth in orthotopic 4T1-bearing mice among the treatment groups. In contrast with single chemotherapy or photothermal therapy, chemo-photothermal treatment by PSC/ICG@+DOX nanoparticles synergistically inhibited the growth of 4T1 cells. Conclusion: This study demonstrated that PSC/ICG@+DOX nanoparticles with active targeting and stimuli-sensitivity would be a promising strategy to enhance chemo-photothermal cancer therapy.

Theaflavin-3,3'-Digallate Inhibits Erastin-Induced Chondrocytes Ferroptosis via the Nrf2/GPX4 Signaling Pathway in Osteoarthritis.

There is evidence that osteoarthritis (OA) is associated with ferroptosis which is a kind of lipid peroxidation-related cell death. Theaflavin-3,3'-digallate(TF3), a polyphenol compound extracted from black tea, possesses antioxidative and anti-inflammatory properties, but its effects on chondrocyte ferroptosis in osteoarthritis (OA) remain unclear. Our present study aims at exploring the protective role and underlying mechanisms of TF3 against erastin-induced chondrocyte ferroptosis in OA. In human primary chondrocytes treated with erastin alone or combined with different doses of TF3, cell viability was assessed by MTS. Ferroptosis-related proteins, including Gpx4, HO-1, and FTH1, were detected by western blot. The levels of lipid peroxidation and Fe2+ were determined by fluorescence staining. Meanwhile, the change of related proteins in the Nrf2/Gpx4 signaling pathway was determined by western blot. siRNA-mediated Nrf2 knockdown and the Gpx4 inhibitor RSL3 were used to explore molecular mechanisms for TF3-induced ferroptosis in OA chondrocyte. The magnetic resonance imaging (MRI), HE staining, Masson's staining, and immunohistochemistry were used to evaluate articular cartilage damages in the rat OA model. The results showed that Gpx4 expression was markedly downregulated in the chondrocytes of OA patients. TF3 reversed erastin-induced ferroptosis of human cultured chondrocytes, lipid ROS, and Fe2+ production in mitochondria. Moreover, the expression of Gpx4, HO-1, FTH1, and Nrf2 was markedly induced by TF3 in the erastin-treated chondrocytes. The antiferroptotic effect of TF3 was related to enhance Nrf2/Gpx4 signaling pathway. Finally, TF3 inhibited OA progression by alleviating in vivo cartilage damage related to chondrocyte ferroptosis. Thus, TF3 significantly inhibits chondrocyte ferroptosis by activating the Nrf2/Gpx4 signaling pathway, suggesting that TF3 serves as a potential therapeutic supplement for OA treatment.

Comparative study of UV/H2O2 and UV/PMS processes for treating pulp and paper wastewater.

Pulp and paper wastewater (PPWW) contains numerous refractory and harmful contaminants that require advanced treatment to meet the discharge criteria. This study compared the efficacy of two PPWW treatments: ultraviolet/peroxymonosulfate (UV/PMS) and ultraviolet/H2O2 (UV/H2O2) working under similar circumstances. The initial pH value, oxidant dosage, UV radiation intensity, and pseudo-first-order constant kobs were systematically studied in both systems. Optimally, the UV/PMS process produced an effluent of higher quality than the UV/H2O2, as measured by the removal efficiencies of chemical oxygen demand (COD) in 60 min, which were 48.2 and 64.3% for the respective UV/H2O2 and UV/PMS processes and corresponding kobs values of 0.0102 and 0.0159 min-1, respectively. Radical scavenging experiments demonstrated that •OH was the primary reactive oxygen species in UV/H2O2 process, and •OH and SO4-• in the UV/PMS process. Moreover, ultraviolet-visible spectroscopy and gas chromatography coupled mass spectroscopy analyses showed that deep treatment of petroleum hydrocarbons with carbon chain lengths greater than 18 and macromolecular semi-volatile organic compounds in paper wastewater is difficult, whereas the UV/PMS process can significantly improve the removal of amides, esters, phenols, and other aromatic compounds.

Polysaccharide from Angelica sinensis attenuates SNP-induced apoptosis in osteoarthritis chondrocytes by inducing autophagy via the ERK1/2 pathway.

OBJECTIVE: Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism. METHOD: Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP. RESULTS: The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway. CONCLUSION: ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.

Discovery of potentially biased agonists of mu-opioid receptor (MOR) through molecular docking, pharmacophore modeling, and MD simulation.

Opioids are well known for their potent analgesic efficacy and severe side effects. Studies have shown that analgesic effects are mediated by the downstream G-protein-dependent pathway of the µ-opioid receptor (MOR), and another ß-arrestin-dependent pathway mediates side effects such as respiratory depression, constipation and tolerance etc. TRV130 is a biased ligand for G-protein-dependent pathway, which has high analgesia and has fewer side effects than morphine. In this study, the structure similarity search was performed on the IBSSC database using Oliceridine (TRV130) and PZM21 as templates. The 3D structure-based pharmacophore model was built and combined molecular docking prediction mode was selected to filter out small molecules, Finally, based on affinity prediction, four candidate molecules were obtained. Molecular dynamics simulations explored the detailed interaction mechanism of proteins with small molecules under dynamics. These results suggest that these candidate molecules are potential MOR agonists.

The discovery, design and synthesis of potent agonists of adenylyl cyclase type 2 by virtual screening combining biological evaluation.

Adenylate cyclases (ACs), play a critical role in the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP). Studies have indicated that adenylyl cyclase type 2 (AC2) is potential drug target for many diseases, however, up to now, there is no AC2-selective agonist reported. In this research, docking-based virtual screening with the combination of cell-based biological assays have been performed for discovering novel potent and selective AC2 agonists. Virtual screening disclosed a novel hit compound 8 as an AC2 agonist with EC50 value of 8.10 µM on recombinant human hAC2 + HEK293 cells. The SAR (structure activity relationship) based on the derivatives of compound 8 was further explored on recombinant AC2 cells and compound 73 was found to be the most active agonist with the EC50 of 90 nM, which is 160-fold more potent than the reported agonist Forskolin and could selectively activate AC2 to inhibit the expression of Interleukin-6. The discovery of a new class of AC2-selective agonists would provide a novel chemical probe to study the physiological function of AC2.

Identification of potential AMPK activator by pharmacophore modeling, molecular docking and QSAR study.

AMP-activated protein kinase (AMPK) plays a major role in maintaining cellular energy homeostasis by sensing and responding to AMP/ADP concentrations relative to ATP. AMPK has attracted widespread attention as a potential therapeutic target for metabolic diseases such as cancer and cardiovascular diseases. The structure-based 3D pharmacophore model was developed based on the training set. The best pharmacophore model Hypo5 was proposed and validated using a decoy set, an external test set. Hypo5, with the correlation coefficient value of 0.936, cost difference value of 112.08 and low RMS value of 1.63, includes a ionizable positive, a hydrogen bond donor, a hydrogen bond acceptor and two hydrophobic features, which showed a high goodness of fit and enrichment factor. Thus it was used as a 3D query to find potential activator from the SPECS Database. Then the ADMET descriptors were used to filter all of 158 screening molecules. The 41 filtering compounds were subsequently subjected to molecular docking and Quantitative structure-activity relationship (QSAR) analysis. Finally, the compound H2 was picked out from those filtering compounds based on the receptor-ligand interaction analysis and the prediction of the QSAR models. And then it was submitted for molecular dynamics (MD) simulations to explore the stability of complex. The result indicates that the candidate could be considered a potential AMPK activator.

Synthesis of Magnetic-Nanoparticle/Ansamitocin Conjugates-Inductive Heating Leads to Decreased Cell Proliferation In Vitro and Attenuation Of Tumour Growth In Vivo.

Conjugates based on nanostructured, superparamagnetic particles, a thermolabile linker and a cytotoxic maytansinoid were developed to serve as a model for tumour-selective drug delivery and release. It combines chemo- with thermal therapy. The linker-modified toxin was prepared by a combination of biotechnology and semisynthesis. Drug release was achieved by hyperthermia through an external oscillating electromagnetic field that induces heat inside the particles. Efficacy of this release concept was demonstrated both for cancer cell proliferation in vitro, and for tumour growth in vivo, in a xenograft mouse model. Biocompatibility studies for these magnetic-nanoparticle/ansamitocin conjugates complement this work.

[Effect of Sinusitis Mixture on Mucosa Cells after Functional Endoscopic Sinus Surgery].

OBJECTIVE: To explore the application of sinusitis mixture (SM) in endoscopic sinussurgery, thereby improving clinical curative rate of chronic sinusitis and nasal polyps. METHODS: A totalof 50 chronic sinusitis patients were equally assigned to the experimental group (nasal douching by SM)and the control group (nasal douching by Compound Sodium Chloride Injection). Mucosa tissue 0.1 cmbefore natural opening was collected before surgery, at week 4, 12, and 24 after surgery. Changes ofmucosa cilia cells, goblet cells, stroma of mucosal membrane, inflammatory cells, and mucous glandwere observed. The numbers of goblet cells in the upper epithelia and ciliated cells, as well as their ratioswere calculated. RESULTS: There was statistical difference in cavity cleaning time, cavity mucosal epithelization time, numbers of goblet cells in the upper epithelia and ciliated cells, as well as their ratio between the two groups (t = -2.342, -2.015, -2.145, respectively; P < 0.05). CONCLUSION: SM could effectively promote and accelerate cleaning and mucosal epithelization of functional endoscopic sinus surgery, and significantly promote mucosal ciliary structure and function recovery of ostium-meatus nasicomplex.

Icariin attenuates titanium-particle inhibition of bone formation by activating the Wnt/ß-catenin signaling pathway in vivo and in vitro.

Wear-debris-induced periprosthetic osteolysis (PIO) is a common clinical condition following total joint arthroplasty, which can cause implant instability and failure. The host response to wear debris promotes bone resorption and impairs bone formation. We previously demonstrated that icariin suppressed wear-debris-induced osteoclastogenesis and attenuated particle-induced osteolysis in vivo. Whether icariin promotes bone formation in a wear-debris-induced osteolytic site remains unclear. Here, we demonstrated that icariin significantly attenuated titanium-particle inhibition of osteogenic differentiation of mesenchymal stem cells (MSCs). Additionally, icariin increased bone mass and decreased bone loss in titanium-particle-induced osteolytic sites. Mechanistically, icariin inhibited decreased ß-catenin stability induced by titanium particles in vivo and in vitro. To confirm icariin mediated its bone-protective effects via the Wnt/ß-catenin signaling pathway, we demonstrated that ICG-001, a selective Wnt/ß-catenin inhibitor, attenuated the effects of icariin on MSC mineralization in vitro and bone formation in vivo. Therefore, icariin could induce osteogenic differentiation of MSCs and promote new bone formation at a titanium-particle-induced osteolytic site via activation of the Wnt/ß-catenin signaling pathway. These results further support the protective effects of icariin on particle-induced bone loss and provide novel mechanistic insights into the recognized bone-anabolic effects of icariin and an evidence-based rationale for its use in PIO treatment.

[The effects of Shadu Cao Mixture on immune functions of immunosuppression mice].

OBJECTIVE: To investigate the effects of Shadu Cao Mixture (SDCM, traditional Chinese medicine) on immune functions of immunosuppression mice. METHODS: Fifty BALB/C mice were randomly divided into blank control group, model group, SDCM low-dose, middle-dose and high-dose group. Except the blank control group, other groups were intraperitoneal injected with cyclophosphamide (40 mg/kg) to establish immunosuppression mice model. The blank control group and model group received gavage administration with nonnal saline, while the other groups received gavage administration with different doses of SDCM (10, 20, 40 m/kg for 15 days) respectively. The number of leukocytes and serum levels of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in peripheral blood, spleen index, and the function of NK cells were measured. RESULTS: Compared with the model group , SDCM increased the number of leukocytes and serum concentrations of IL-2, TNF-α and IFN-γ in peripheral blood and improved the spleen index and the function of NK cells significantly (P < 0.05-0.01). CONCLUSION: SDCM could remarkably enhance the immune functions of immunosuppression mice induced by cyclophosphamide.