Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

Objective:To explore the association between changes in brain structural network during the early stage of stroke recovery and the onset of post-stroke depression (PSD).Methods:A total of 87 acute ischemic stroke patients scheduled for discharge, who were admitted to the Yixing Hospital Affiliated to Jiangsu University from March 2020 to May 2021, were prospectively collected. During the same period, 34 healthy control subjects matched with the stroke patients were also collected. All participants underwent systematic magnetic resonance imaging scans and scale assessments, and were followed up longitudinally for 2 years. Based on the occurrence of depression during follow-up, the stroke patients were divided into PSD group and post-stroke non-depression (PSND) group. Graph theoretical analysis was used to analyze the topological characteristics of brain structural network. Analysis of variance was used to explore the differences in brain structural network attributes among groups. Logistic regression model was used to analyze the predictive power of differential brain network attributes for PSD. Linear regression analysis was conducted to investigate the relationship between the synergism of non-rich-club regions and changes in rich-club connectivity.Results:The rich-club connectivity and synergism of the non-rich-club regions were significantly lower in the PSD group than in the PSND group (rich-club connectivity, P<0.01; synergism of feeder/local, P<0.001). The regression model demonstrated that the synergism of non-rich-club regions had a good predictive power for the occurrence of PSD ( OR=1.195, 95%CI 1.073-1.471, P<0.001). Furthermore, linear regression analysis revealed a significant correlation between the synergism of non-rich-club regions and Δrich-club connectivity ( r=-0.691, P<0.001). Conclusion:The good synergism of non-rich-club regions during the early stage of stroke recovery promotes the repair of rich-club connectivity and inhibits the onset of PSD.

Nerve dysfunction is a common postoperative complication of dental extractions. In dental extraction, the nerves involved mainly include the inferior alveolar nerve, lingual nerve, buccal nerve, chin nerve and nasopalatine nerve. Nerve dysfunction will seriously affect the patient′s quality of life and may lead to medical disputes. This review firstly summarizes the clinical manifestations and pathological mechanisms of post-dental extraction nerve dysfunction, then summarizes its clinical risk factors and preventive strategies, then analyzes the clinical characteristics and physiological mechanisms of natural sensory recovery after dental extraction nerve dysfunction, and finally summarizes the cutting-edge therapeutic tools and research directions in the treatment of post-dental extraction nerve dysfunction in recent years. The aim of this article is to comprehensively review the cutting-edge advances in post-dental extraction nerve dysfunction from clinical to molecular mechanisms, and from pathogenesis to prevention and treatment strategies, and seeks to provide reference for oral surgeons in preventing and responding to the treatment of nerve dysfunction after dental extraction.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

Objective To investigate the optimal gamma passing rate of intensity-modulated radiotherapy (IMRT) dosimetric verification in the treatment of esophageal cancer using a three-dimensional dose verification system EDoseTM.Methods Twenty five esophageal cancer patients treated by 7-field IMRT were retrospectively reviewed.Measured dose distribution were reconstructed on CT image and evaluated by gamma analysis and DVH metrics using the EDoseTM system.Plans with DVH metrics dose difference ＜ 5％ or with gamma passing ＞ 90％ under 3％/3 mm criteria were accepted.The optimal gamma passing rate for criteria of 5％/3 mm,3％/3 mm,2％/2 mm were investigated by drawing the receiver operating characteristic (ROC) curves and calculating the Youden Index.The sensitivity and specificity of the these optimal thresholds in the plan verification were also analyzed.Results The optimal thresholds for global gamma indices with 5％/3 mm,3％/3 mm,2％/2 mm were 98.66％,94.84％,78.56％,respectively.In the 90％ common threshold,The sensitivity and specificity for common 90％ threshold and optimal threshold under 3％/3 mm criteria were 0.17 vs.0.85 and t 0.84 vs.0.27,respectively.The sensitivity and specificity were 0.89,0.65 and 0.23,0.47 for optimal thresholds under 5％/3 mm and 2％/2 mm criteria,respectively.Conclusions The sensitivity of optimal threshold gamma passing rate improved significantly compared with the common threshold (90％) at 3％/3 mm criteria.,The sensitivity and the specificity were more balanced at the 2％/2 mm criteria compared with those at 3％/3 mm criteria.

OBJECTIVE: To investigate the surgical method of plerosising intra-orbital wall blow-out fracture through ethmoid sinuses under trans-nasal endoscopy with the graft of nasal septal cartilage. METHOD: Eighteen patients who encounter the intra-orbital wall blow-out fracture were plerosised under trans-nasal endoscopy through ethmoid sinuses. As a part of the surgical method, the nasal septal cartilage was taken as the graft. We analyzed the curative effect of the method. RESULT: The follow-up was from half a year to one year, all of the 18 patients met the cure standards without the graft prolapsus. CONCLUSION It is a feasible surgical method to plerosis intra-orbital wall blow-out fracture under the endoscopic transnasal with the graft of nasal septal cartilage through ethmoid sinuses, which is direct-viewing,micro- trauma, well-histocompatibility and so on.
Adolescent ; Adult ; Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Nasal Cartilages ; surgery ; Nasal Septum ; surgery ; Orbital Fractures ; surgery ; Young Adult