辽宁医学院

5522 Background: Enlonstobart is a PD-1 inhibitor that has demonstrated durable anti-tumor activity and acceptable safety in patients with PD-L1 positive recurrent/metastatic cervical cancer in a multicenter, single-arm, open-label, phase II study. At primary cutoff date (May 27, 2023), the overall survival (OS) was not reached. Here, we report results from a pre-planned further follow-up (August 20, 2024). Methods: Eligible patients were ≥18 years old with PD-L1-positive (combined positive score ≥ 1) cervical cancer who had progression during or after or intolerance to the first-line platinum-based therapy. A total of 107 patients received enlonstobart 240 mg every two weeks for up to 24 months or until disease progression, intolerable toxicities, or other study discontinuation criteria were met. At the updated cutoff date, analyses of progression-free survival (PFS) and OS in the full analysis set (FAS), which consisted of all patients who had received at least one dose of enlonstobart treatment, and the per protocol set (PPS), which consisted of all patients in the FAS who had at least one available postbaseline tumor assessment were conducted. Results: At the cutoff date of August 20 2024, the median follow-up time was 15.84 months (range 0.4 ~ 35.6 months). In FAS, the median PFS was 3.06 (95 % CI 2.23–6.90) months. The median OS was 19.38 (95 % CI 14.95–25.40) months and the estimated OS rate was 68.14 % (95 %CI 58.20–76.19) at 12 months, 50.78 % (95 % CI 40.46–60.20) at 18 months, and 42.84 % (95 % CI 32.76–52.53) at 24 months. In PPS, the median PFS was 3.81 (95 % CI 2.63–7.49) months. The median OS was 21.26 (95 % CI 15.44–27.66) months and the estimated OS rate was 71.53 % (95 %CI 61.48–79.40) at 12 months, 53.32 % (95 % CI 42.64–62.87) at 18 months, and 44.98 % (95 % CI 34.50–54.89) at 24 months. Conclusions: Enlonstobart monotherapy showed a promising survival in patients with PD-L1 positive recurrent/metastatic cervical cancer, whose disease experienced progression after first-line platinum-based therapy. Clinical trial information: NCT04886700 .

Light is an efficient technique that has a significant influence on contemporary medicine. Photodynamic therapy (PDT), which involves the combined action of photosensitizers (PSs), oxygen, and light, has emerged as a therapeutically promising method for treating a broad variety of solid tumors and infectious diseases. Photodynamic therapy is minimally invasive, has few side effects, lightens scars, and reduces tissue loss while preserving organ structure and function. In particular, PDT has a high healing potential for wounds (PDT stimulates wound healing by enhancing re-epithelialization, promoting angiogenesis as well as modulating skin homeostasis). Wound healing involves interactions between many different processes, including coagulation, inflammation, angiogenesis, cellular migration, and proliferation. Poor wound healing with diabetes or extensive burns remains a difficult challenge. This review emphasizes PDT as a potential research field and summarizes PDT's role in wound healing, including normal wounds, chronic wounds, and aging wounds.

Background: Bladder urothelial carcinoma (BUC) is a type of malignant urinary system. Although several strategies have been applied in the treatment of BUC, its survival remains unsatisfactory, especially in the patients with advanced BUC. Vitexin, a natural flavonoid has exhibited the inhibitory effect on various tumors, however, its effect on BUC is still unclear. Objective: This study aimed to explore the effect of vitexin on the progression of BUC. Methods: The toxicity of vitexin on T24 and 5637 cells was detected by cell counting kit-8 (CCK-8). The effects of vitexin on proliferation, apoptosis, invasion, epithelial-mesenchymal transition (EMT) and ferroptosis in BUC cells were determined by CCK-8, flow cytometry, western blot, transwell and immunofluorescence assays. Additionally, the related mechanism was explored by examining the expression of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)-nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway. Besides, in vivo validation was performed in the xenografted mice. Results: Vitexin reduced the BUC cell viability and enhanced the apoptosis rate and the relative protein expression of p53 and cleaved-caspase3. Also, vitexin decreased the invasion number, and increased the relative protein expression of E-cadherin with the decreased N-cadherin protein level in T24 and 5637 cells. Besides, vitexin promoted the levels of ROS and MDA, while reduced the GSH level. Vitexin also increased the level of iron, but decreased the relative protein expression of xCT and GPX4. Erastin further increased the vitexin-induced iron levels, whereas inverse outcomes were observed in the application of ferrostatin-1. Additionally, vitexin decreased the relative protein levels of PI3K, p-AKT/AKT, and nuclear Nrf2, while increased the relative protein level of cytoplasmic Nrf2. Overexpression of PI3K notably inverted the effect of vitexin on cell viability, apoptosis, invasion, level of ROS and iron. Furthermore, vitexin reduced the tumor volume and weight of xenografted mice. Vitexin decreased the protein level of N-cadherin, while increased apoptosis rate of xenografted mice. In addition, vitexin reduced the relative protein levels of PI3K, p-AKT/AKT, and nuclear Nrf2 with the enhanced relative protein expression of cytoplasmic Nrf2 in xenografted mice. Moreover, vitexin decreased the relative protein expression of xCT and GPX4 and the GSH level, whereas increased the MDA level in xenografted mice. Conclusion: Vitexin suppressed malignant proliferation and invasion and induced apoptosis and ferroptosis of BUC involving in PI3K/AKT-Nrf2 pathway.

Osteoarthritis (OA) is a multifaceted disease characterized by imbalances in extracellular matrix metabolism, chondrocyte and synoviocyte senescence, as well as inflammatory responses mediated by macrophages. Although there have been notable advancements in pharmacological and surgical interventions, achieving complete remission of OA remains a formidable challenge, oftentimes accompanied by significant side effects. Mesenchymal stem cells (MSCs) have emerged as a promising avenue for OA treatment, given their ability to differentiate into chondrocytes and facilitate cartilage repair, thereby mitigating the impact of an inflammatory microenvironment induced by macrophages. This comprehensive review aims to provide a concise overview of the diverse roles played by MSCs in the treatment of OA, while elucidating the underlying mechanisms behind these contributions. Specifically, the roles include: (a) Promotion of chondrocyte and synoviocyte regeneration; (b) Inhibition of extracellular matrix degradation; (c) Attenuating the macrophage-induced inflammatory microenvironment; (d) Alleviation of pain. Understanding the multifaceted roles played by MSCs in OA treatment is paramount for developing novel therapeutic strategies. By harnessing the regenerative potential and immunomodulatory properties of MSCs, it may be possible to devise more effective and safer approaches for managing OA. Further research and clinical studies are warranted to optimize the utilization of MSCs and realize their full potential in the field of OA therapeutics.

Neonatal clinical sepsis is recognized as a significant health problem, This study sought to identify a predictive model of risk factors for clinical neonatal sepsis. A retrospective study was conducted from 1 October 2018 to 31 March 2023 in a large tertiary hospital in China. Neonates were divided into patients and controls based on the occurrence of neonatal sepsis. A multivariable model was used to determine risk factors and construct models.The utilization and assessment of model presentation were conducted using Norman charts and web calculators, with a focus on model differentiation, calibration, and clinical applicability (DCA). Furthermore, the hospital’s data from 1 April 2023 to 1 January 2024 was utilized for internal validation. In the modelling dataset, a total of 339 pairs of mothers and their newborns were included in the study and divided into two groups: patients (n = 84, 24.78%) and controls (n = 255, 75.22%). Logistic regression analysis was performed to examine the relationship between various factors and outcome. The results showed that maternal age < 26 years (odds ratio [OR] = 2.16, 95% confidence interval [CI] 1.06–4.42, p = 0.034), maternal gestational diabetes (OR = 2.17, 95% CI 1.11–4.27, p = 0.024), forceps assisted delivery (OR = 3.76, 95% CI 1.72–5.21, p = 0.032), umbilical cord winding (OR = 1.75, 95% CI 1.32–2.67, p = 0.041) and male neonatal sex (OR = 1.59, 95% CI 1.00–2.62, p = 0.050) were identified as independent factors influencing the outcome of neonatal clinical sepsis. A main effects model was developed incorporating these five significant factors, resulting in an area under the curve (AUC) value of 0.713 (95% CI 0.635–0.773) for predicting the occurrence of neonatal clinical sepsis. In the internal validation cohort, the AUC value of the model was 0.711, with a 95% CI of 0.592–0.808. A main effects model incorporating the five significant factors was constructed to help healthcare professionals make informed decisions and improve clinical outcomes.