GELATIN-BASED BIOMATERIALS FOR DRUG AND CELL DELIVERY

Ph.DDOCTOR OF PHILOSOPH

The Emergence of Complexity: Lessons from DNA

The same molecular qualities that endowed DNA with its capacity to carry hereditary information make it a powerful tool to explore the self-assembly of complex nanostructure

Formation and characteristic corrosion behavior of alternately lamellar arranged α and β in as-cast AZ91 Mg alloy

Formation and characteristic corrosion resistance of alternately lamellar arranged α and β in as-cast AZ91 Mg alloy were investigated as an independent micro-constituent identity. As-cast AZ91 presented three microstructural entities, i.e. α-Mg grain, (α+β) lamellae and coarse β particle, and each had its own Al content and microstructural morphology. The lamellae occurrence was due to the precipitation of β particle from the divorced eutectic Al-rich-α phase during solidification, because the Al composition can not exceed its maximum solubility. The evidences that were obtained from electrochemical tests, micro-corrosion morphology and hydrogen evolution rate certified that the (α+β) lamellae was beneficial to corrosion resistance, which was different from the reported deleterious influence for its original eutectic Al-rich-α phase. This different corrosion behavior was explained to be ascribed to the changes in fine structure and local composition that resulted in combined electrochemical effects of the changes in α and β phases on the corrosion

Cytomegalovirus Infection May Trigger Adult-Onset Still's Disease Onset or Relapses

Previous studies have revealed that several micro-organisms, especially DNA viruses, have been associated with adult-onset Still's disease (AOSD). However, there are no studies on the relationship between the presence of viral infections in AOSD patients with disease occurrence and reactivation. In the present study, we aimed to investigate the presence of antibodies against virus, virus DNA load and nucleic acid sensors in AOSD patients. Anti-viral antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples from 100 AOSD patients and 70 healthy controls (HCs). The copy number of cytomegalovirus (CMV) DNA in 100 AOSD patients was detected by PCR. The expression levels of nucleic acid sensors interferon gamma-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) in peripheral blood mononuclear cell (PBMC) and skin from AOSD patients and HCs were analyzed by PCR and immunohistochemistry. The levels of antibodies against CMV were significantly higher in AOSD patients compared to HCs. Moreover, the level of anti-CMV IgM antibody was significantly increased in patients with fever, sore throat, arthralgia and rash. CMV DNA was found in plasma of AOSD patients with disease new-onset and relapse. Furthermore, the copy number of CMV DNA significantly increased in patients with fever, sore throat, arthralgia and rash. And the significant associations of the CMV DNA level with the levels of leukocytes, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were observed. Moreover, we found an upregulation of cytoplasmic DNA-sensing receptor IFI16 and AIM2 in PBMC and skin from AOSD patients. In conclusion, our results showed that CMV infection may play a role in the initiation or amplification of inflammatory responses in AOSD

Plasma microRNA Profiles as a Potential Biomarker in Differentiating Adult-Onset Still's Disease From Sepsis

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by cytokine storm. However, a diagnostic test for AOSD in clinical use is yet to be validated. The aim of our study was to identify non-invasive biomarkers with high specificity and sensitivity to diagnosis of AOSD. MicroRNA (miRNA) profiles in PBMC from new-onset AOSD patients without any treatment and healthy controls (HCs) were analyzed by miRNA deep sequencing. Plasma samples from 100 AOSD patients and 60 HCs were used to validated the expression levels of miRNA by qRT-PCR. The correlations between expression levels of miRNAs and clinical manifestations were analyzed using advanced statistical models. We found that plasma samples from AOSD patients showed a distinct miRNA expression profile. Five miRNAs (miR-142-5p, miR-101-3p, miR-29a-3p, miR-29c-3p, and miR-141-3p) were significantly upregulated in plasma of AOSD patients compared with HCs both in training and validation sets. We discovered a panel including 3 miRNAs (miR-142-5p, miR-101-3p, and miR-29a-3p) that can predict the probability of AOSD with an area under the receiver operating characteristic (ROC) curve of 0.8250 in training and validation sets. Moreover, the expression levels of 5 miRNAs were significantly higher in active AOSD patients compared with those in inactive patients. In addition, elevated level of miR-101-3p was found in AOSD patients with fever, sore throat and arthralgia symptoms; the miR-101-3p was also positively correlated with the levels of IL-6 and TNF-α in serum. Furthermore, five miRNAs (miR-142-5p, miR-101-3p, miR-29c-3p, miR-29a-3p, and miR-141-3p) expressed in plasma were significantly higher in AOSD patients than in sepsis patients (P < 0.05). The AUC value of 4-miRNA panel (miR-142-5p, miR-101-3p, miR-29c-3p, and miR-141-3p) for AOSD diagnosis from sepsis was 0.8448, revealing the potentially diagnostic value to distinguish AOSD patients from sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as a potential non-invasive biomarker for diagnosis of AOSD and monitoring disease activity

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Improving Hydrophilicity and Inducing Bone-Like Apatite Formation on PPBES by Polydopamine Coating for Biomedical Application

Copoly(phthalazinone biphenyl ether sulfone) (PPBES) as a commercially available polyarylether is a promising orthopaedic implant material because its mechanical properties are similar to bone. However, the bioinert surface of polyarylether causes some clinical problems after implantation, which limits its application as an implant material. In this study, the surface of PPBES was modified by a biomineralization method of polydopamine-assisted hydroxyapatite formation (pHAF) to enhance its cytocompatibility. Polydopamine (PDA) coating, inspired by the adhesion mechanism of mussels, can readily endow PPBES with high hydrophilicity and the ability to integrate via the bone-like apatite coating. PPBES and PDA-coated PPBES were evaluated by scanning electronic microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. The water contact angles were reduced significantly after coating with PDA. PDA was successfully synthesized on PPBES and more PDA was obtained by increasing the temperature. Bone-like apatite on PPBES (apatite-coated PPBES) was confirmed by SEM and transmission electron microscopy (TEM). The cytotoxicity of pristine PPBES and apatite-coated PPBES were characterized by culturing of NIH-3T3 cells. Bone-like apatite synthesized by pHAF could further enhance cytocompatibility in vitro. This study provides a promising alternative for biofunctionalized PPBES with improved cytocompatibility for bone implant application