Diabetic kidney disease （DKD）， a common complication of diabetes mellitus， is a leading global cause of end-stage renal disease （ESRD）. Current therapeutic strategies primarily focus on symptomatic management but exhibit limited efficacy in halting disease progression to ESRD， and some drugs carry non-negligible toxic side effects. Traditional Chinese medicine （TCM） has a long history in treating DKD， with single TCM and TCM compounds demonstrating unique advantages in multi-target， multi-pathway， and multi-effect therapeutic interventions. Tripterygium wilfordii （TW）， known for its effects in promoting blood circulation， dredging collaterals， dispelling wind， removing dampness， reducing swelling， and alleviating pain， contains bioactive components such as Tripterygium glycosides （TWG）， triptolide （TPL）， tripdiolide （TPD）， and celastrol （CEL）. The active ingredients possess various functions， including regulating immune-inflammatory balance， ameliorating renal fibrosis and glomerulosclerosis， combating oxidative stress， protecting podocytes， and improving glucose and lipid metabolism， all of which play a significant role in the treatment of DKD. This review summarized the mechanisms underlying the therapeutic effects of T. wilfordii and its active ingredients on DKD， aiming to provide insights for clinical management and novel drug development of DKD.

Palliative care is a way to help end-of-life populations improve their quality of life， and its development in practice cannot be separated from the level of education in palliative care. At present， some medical schools in palliative care education compared with western developed countries have problems such as imperfect construction of hospice curriculum system， lack of medical students’ hospice knowledge； insufficient interdisciplinary teaching faculty， weak palliative care awareness of medical students； single teaching evaluation mode； weak palliative care practice teaching links. To this end， it is necessary to improve the palliative care curriculum system， explore rich and diverse teaching methods； strengthen interdisciplinary teaching and faculty development， enhancing the awareness of palliative care among medical students；establish a scientific and effective evaluation method， carry out multi-dimensional dynamic assessment； expand the palliative care practice teaching base， and accurately improve the practical skills of medical students in palliative care， and other countermeasures to improve the level of palliative care education， and to help the strategy of Healthy China.

Immunoglobulin A nephropathy （IgAN） is a common primary glomerular disease and a frequent cause of chronic renal failure. Tripterygium wilfordii is a traditional Chinese herbal medicine， which possesses the effects of promoting blood circulation， relieving swelling and pain， and dispelling wind and dampness. Modern pharmacological studies have shown that T. wilfordii multiglucoside exhibit anti-inflammatory and immunomodulatory effects， inhibit mesangial cell proliferation， protect podocytes， ameliorate endothelial cell injury， and regulate gut microbiota disturbances. Triptolide also possesses anti-inflammatory and immunomodulatory properties， suppresses mesangial cell proliferation， and protects podocytes. Celastrol demonstrates anti- inflammatory and immunomodulatory functions as well as the ability to improve endothelial cell damage. Through these mechanisms， T. wilfordii and its active components can play a role in alleviating clinical symptoms and delaying disease progression in the treatment of IgAN. Future research should focus on in-depth analysis and mechanistic investigation of these active ingredients， promote high-quality clinical studies， systematically evaluate the synergistic effects among them， and emphasize strategies for reducing toxicity and enhancing efficacy， thereby providing more comprehensive and reliable evidence-based foundations for the clinical treatment of IgAN.

Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

Chronic wounds, defined as persistent failure to heal due to specific etiological factors, remain a major clinical challenge. Current standard interventions such as negative pressure wound therapy are limited by complications like hypergranulation and poor patient compliance, while emerging stem cell-based therapies carry potential tumorigenic risks. Consequently, identifying strategies to safely and effectively accelerate wound healing continues to be a critical focus in contemporary clinical research. Platelet-rich plasma derived extracellular vesicles (PRP-EVs) are extracellular vesicles released by platelets after activation. They have the characteristics of autologous origin, higher safety, and more mild and convenient clinical application. Studies have shown that PRP-EVs are rich in bioactive molecules such as lipids, proteins and RNA, which have outstanding performance in regulating wound inflammation, promoting angiogenesis, enhancing cell migration and proliferation, and are expected to become an effective tool for the treatment of chronic wounds. This review discusses the methods, mechanisms of action, and challenges associated with the use of PRP-EVs in chronic wound management, providing a foundation for future research and clinical applications in this field.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective To prepare neutrophil-responsive luminescent nanomicelles based on self-luminating compound,luminol,and investigate their imaging capability for a mouse burn model at early stage of inflammation.Methods Hexachlorotripolyphosphazene(HCCP)was utilized as the skeleton material to synthesize amphiphilic LHP luminescence materials through chemical synthesis of luminol and polyethylene glycol(PEG).The chemical structure of LHP was characterized using infrared spectrum and nuclear magnetic hydrogen spectrum.Nanomicelle LHP NM was formed by self-assembly of LHP in deionized water,and then its particle size and potential were measured.Transmission electron microscopy(TEM)was applied to observe the morphology of nanomicelles.Optical fiber spectrometer,weak luminescence measuring instrument,and small animal living imager were employed to evaluate the spectroscopic properties,chemiluminescence rules,and in vitro luminescence imaging ability of the nanomicelles.After that,female Balb/c mice were subjected to scalding with hot water at temperatures of 70℃,80℃,and 90℃,respectively to establish a mouse burn model ranging from degree Ⅰ to degree Ⅱ burns.The depth of skin scalds in the model mice was determined through HE staining,while the expression levels of TNF-α,IL-1β,IL-6 and myeloperoxidase(MPO)in the scalded skin tissues were assessed with fluorescence quantitative qPCR.The changes in reactive oxygen species(ROS)levels over time and burn depth in the skin tissues were determined with ROS detection kit.Additionally,the neutrophils within the skin tissues of model mice were labeled with FITC-Ly6G antibody to count the neutrophil number.Finally,a small animal imaging system was utilized to examine the imaging capability of nanomicelle LHP NM in a mouse burn model to analyze the correlation between luminous intensity and number of recruited neutrophil in order to evaluate the effectiveness of luminous nanomicelles for monitoring early inflammatory response and diagnosing burn depth in a mouse burn model.Results Nuclear magnetic resonance(NMR)spectroscopy confirmed the bonding of approximately 5 luminol units and a polyethylene glycol(PEG)chain to 1 HCCP molecule.TEM and particle size determination results demonstrated that the prepared nanomicelles were spherical,hollow structures in a diameter of around 120 nm.In vitro luminescence experiments revealed that the nanomicelles exhibited high brightness and sustained chemiluminescence under varying concentrations of ROS and MPO levels,with luminescence intensity dependent on both ROS level and nanomicelle concentration.The in vitro cellular experiments demonstrated that the nanomicelles exhibited neutrophil-responsive imaging capability.The luminescence intensity was positively correlated with both the number of neutrophils and the dose of LHP NM,with a linear correlation coefficient(r)of 0.98 and 0.99,respectively.In vivo animal study revealed a significant increase(P<0.05)in the count of neutrophils and ROS level in the skin tissue of burned and scalded mice.Notably,at the time point of 24 h,compared to the 80℃and 70℃treatment groups,the number of recruited neutrophils was increased by 86.4％,and the luminescent imaging intensity rose by 71.5％.These findings indicated that the severity of burns was correlated with the extent of neutrophil recruitment in the injured area,and LHP NM could effectively achieve neutrophil-responsive imaging in model mice.The changes in imaging intensity were closely associated with the number of neutrophils and the level of ROS in the injured skin tissue.Conclusion The neutrophil-responsive luminescent nanomicelle LHP NM is successful prepared,and the nanomicelles enable responsive imaging of skin damage in mouse burn model.The luminescence intensity accurately reflects the neutrophil infiltration and ROS level,allowing for real-time monitoring of early inflammatory responses in mouse burn model.Additionally,this study provides methods and strategies for diagnosing burn depth.