BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

BackgroundThe professional self-concept of nurses is a crucial indicator for their personal growth， development and career planning. Previous studies have shown that work stressors during the internship period may lead to a decrease in the level of professional self-concept among nursing students. Given the existing differences in social roles between nursing students and clinical nurses， the influencing factors of professional self-concept in clinical nurses and its relationship with work stressors require further research. ObjectiveTo explore the relationship between work stressors and professional self-concept among nurses， so as to provide references for improving the level of professional self-concept of clinical nurses. MethodsFrom December 2022 to February 2023， a stratified random sampling method was employed to select 260 in-service nurses from Mianyang Hospital of Traditional Chinese Medicine as the study subjects. Chinese Nurses Stressor Scale （CNSS） and Professional Self-concept of Nurses Instrument （PSCNI） were used for assessment. Pearson correlation analysis was conducted to examine the correlation between CNSS scores and PSCNI scores of nurses. Multiple linear regression analysis was utilized to explore the factors influencing the professional self-concept of nurses. ResultsA total of 238 nurses （91.54%） completed valid questionnaires. PSCNI total score yielded a statistical difference among nurses with different marital statuses （F=8.947， P<0.05）. PSCNI total scores were significantly higher in nurses with emergency medical service experience than those without such experience （t=2.208， P<0.05）， and were significantly lower in nurses with abnormal physical examination findings in the past year than those without abnormal findings （t=-2.584， P<0.05）. Correlation analysis revealed that CNSS total score and subscale scores were negatively correlated with PSCNI total score （r=-0.275~-0.169， P<0.01）. Multiple linear regression analysis indicated that work expectation-related stressors， marital status and emergency medical service experience might be influencing factors of their professional self-concept （β=-0.350， 0.345， 0.183， P<0.01）. ConclusionNurses' work stressors are closely correlated with their professional self-concept， and high levels of stressors related to nurses' expectations may lead to a decrease in their professional self-concept levels. ［Funded by 2021 Research Project of Mianyang Municipal Health Commission （number， 202154）］

Objective This study aims to explore the efficacy and complication rates of the transcranial approach(TCA)and extended endoscopic endonasal approach(EEEA)for the treatment of craniopharyngiomas based on the QST classification,providing a scientific reference for clinical decision-making on surgical approach.Methods A total of 151 patients who underwent craniopharyngioma surgery at our center from January 2018 to December 2023 were enrolled.The patients were categorized into Q-CP(suprasellar type),S-CP(infundibular type),and T-CP(tuberal type)according to the QST classification.Systematic collection and analysis were performed on the outcomes of TCA and EEEA treatments,respectively.The differences in effectiveness between the two approaches were evaluated based on the QST classification.Results The improvement rate of visual symptoms was overall higher in the EEEA group than in the TCA group(59.1%vs.36.5%,P=0.006),and the visual deterioration rate was lower(3.0%vs.14.1%,P=0.006).However,the incidence of cerebrospinal fluid leakage was higher in the EEEA group(15.2%vs.3.5%,χ2=4.986,P=0.026).The incidence of postoperative seizures(8.2%vs.0,P=0.019),brain contusions(10.6%vs.0,P=0.005),and subdural hematoma(9.4%vs.0%,P=0.01)was higher in the TCA group.For patients with Q-CP type,the EEEA group had a higher rate of total tumor resection(92.9%vs.65.2%,P=0.025)and a lower recurrence rate(3.6%vs.21.7%,P=0.047),with shorter hospital stays and lower postoperative costs.The TCA group had higher intraoperative blood loss in this type(300 mL vs.200 mL,Z=-2.261,P=0.024).For S-CP type patients,the EEEA group showed a higher rate of total tumor resection(91.3%vs.74.2%)and a lower recurrence rate(0 vs.12.9%,P=0.031),with lower postoperative hospital costs.In T-CP type,due to the deeper location,EEEA showed limitations in protecting hypothalamic function and the TCA group had a better postoperative hypothalamic function score(P=0.035).Conclusion Based on QST classification,EEEA has advantages in Q-CP and S-CP types and is recommended as the preferred surgical procedure;In the T-CP type,TCA surgery is more helpful in protecting hypothalamic function.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which seriously threatens the vision of patients. The pathogenesis of DR Is complex and involves many pathophysiological processes. At present, the treatment methods for DR Mainly include panretinal laser photocoagulation, vitrectomy and vitreous cavity injection, etc. However, each treatment method has certain limitations. In recent years, remarkable progress has been made in the field of drug treatment of DR, especially in anti-vascular endothelial growth factor drugs, anti-inflammatory drugs, anti-oxidative stress damage drugs, neuroprotective agents, gene therapy and stem cell therapy. These drugs not only improve the effectiveness of treatment, but also expand the range of treatment options. In addition, by carrying DR Treatment drugs on carriers such as nanoparticles, hydrogels and photosensitive materials, continuous and efficient release of drugs in the eye is achieved, thereby extending the time interval of administration and reducing the need for frequent treatment of patients. In the future, based on biomarker detection technology, it is expected to promote the development of personalized and precise treatment, which can develop more accurate treatment plans for patients and improve the efficacy.

Objective:To investigate the clinical efficacy and factors influencing treatment of pediatric noninfectious uveitis with Adalimumab (ADA).Methods:A retrospective clinical study. A total of 86 pediatric patients with non-infectious uveitis, diagnosed and treated with ADA at Department of Uveitis Specialist of Xi'an People's Hospital (Xi' an Fourth Hospital) from January 1, 2021 to December 31, 2023, were included in this study. The age of all patients was ≤16 years. Among them, 55 (63.95%, 55/86) patients received ADA combined with one immunosuppressive agent, 28 (32.56%, 28/86) patients received ADA combined with ≥2 immunosuppressive agents, and 3 (3.49%, 3/86) patients received ADA alone without any immunosuppressive agents. All patients underwent best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. The thickness of the retinal nerve fiber layer (RNFL) in the macular region was measured using an OCT device. The cumulative treatment effectiveness rate at 12 months post-treatment was evaluated using the Kaplan-Meier survival analysis. Multivariate analysis was performed using the Cox proportional hazards regression model, and the optimal predictive model was selected based on the Bayesian information criterion. The association between different treatment regimens and various clinical outcomes was assessed.Results:Among the 86 pediatric patients, 42 were male and 44 were female, with a mean age of (10.47±3.23) years. The distribution of uveitis types was as follows: anterior uveitis in 37 cases, intermediate uveitis in 15 cases, posterior uveitis in 10 cases, and panuveitis in 24 cases. Anterior chamber cells (ACC), keratic precipitates, and synechiae were present in 66, 55, and 38 cases, respectively. The cumulative treatment effectiveness at 12 months was 85.1% [95% confidence interval ( CI) 71.9-92.2], with a median time to treatment effectiveness of 3 months. Compared with baseline, after 6 months of treatment, the BCVA, RNFL thickness ( Z=?6.323, ?8.017), and the grading of ACC and vitreous haze ( χ2= ?6.917, ?5.027) showed significant improvement, with statistically significant differences ( P<0.05). Multivariate analysis revealed that ACC (hazard ratio=22.31, 95% CI 2.43-204.68) and anterior uveitis (hazard ratio=3.88, 95% CI 2.03-7.42) were significantly associated with treatment effectiveness ( P<0.05). Patients with ACC had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 95.5% (95% CI 86.3-98.5). Patients with anterior uveitis had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 97.3% (95% CI 81.3-99.6). Patients without anterior uveitis had a median time to treatment effectiveness of 5 months, with a 12-month cumulative treatment effectiveness of 76.7% (95% CI 54.1-88.2). The cumulative recurrence risk at 12 months was 15.6% (95% CI 6.2-24.1). Conclusion:ADA is safe and effective in treating pediatric non-infectious uveitis, and ACC and anterior uveitis are associated with response rate.

BACKGROUND:Vital pulp therapy is one of the main treatments for common oral diseases such as deep caries.The antibacterial properties of pulp-capping materials are crucial to the efficacy of the treatment.Currently,commonly used pulp-capping material has weak antibacterial properties and may induce a certain degree of inflammatory response in the pulp tissue,leading to treatment failure.OBJECTIVE:To investigate the antibacterial effects of nanosilver-reduced graphene oxide/polydopamine/methacrylated gelatin@Gap19(AgNPs-rGO/PDA/GelMA@Gap19)hydrogel material.METHODS:Nanosilver-reduced graphene oxide was prepared.Human dental pulp stem cells were cultured in complete medium containing different mass concentrations of nanosilver-reduced graphene oxide.Cell proliferation was detected by CCK-8 assay.The inhibition zone assay was used to detect the inhibitory effect of different mass concentrations of nanosilver-reduced graphene oxide on Staphylococcus aureus.The nanosilver-reduced graphene oxide mass concentration with the most obvious cell proliferation and antibacterial effects was screened by the results of CCK-8 and inhibition zone assays,and loaded into hydrogels.Human dental pulp stem cells were cultured in complete medium containing different concentrations of Gap19(a specific inhibitor of connexin 43 hemichannels),and cell proliferation was detected by CCK-8 assay.The Gap19 concentration with the most obvious cell proliferation effect was screened and loaded into hydrogels.AgNPs-rGO/PDA/GelMA@Gap19 hydrogel was prepared,and the physicochemical properties of the hydrogel material were characterized.The suspension of Staphylococcus aureus(or Escherichia coli,Streptococcus mutans,Lactobacillus)was co-cultured with mineral trioxide aggregates,polydopamine/methacrylated gelatin hydrogel,nanosilver-reduced graphene oxide/polydopamine/methacrylated gelatin hydrogel and AgNPs-rGO/PDA/GelMA@Gap19 hydrogel.The bacterial suspension cultured alone was used as the blank control group to detect the antibacterial rate of each group of hydrogels.RESULTS AND CONCLUSION:(1)The optimal mass concentration of nanosilver-reduced graphene oxide was determined to be 12.5 μg/mL by CCK-8 assay and inhibition zone test results,and the optimal concentration of Gap19 was determined to be 20 μmol/L by CCK-8 assay.(2)Scanning electron microscopy showed that AgNPs-rGO/PDA/GelMA@Gap19 hydrogel was wrinkled and porous,and nanosilver was loaded on the surface and inside of the hydrogel.Energy spectrum analysis results showed that nanosilver-reduced graphene oxide and Gap19 were successfully loaded on the hydrogel.(3)The four hydrogels had obvious inhibitory effects on Staphylococcus aureus,Escherichia coli,Streptococcus mutans,and Lactobacillus,and the antibacterial effects of nanosilver-reduced graphene oxide/polydopamine/methacryloyl gelatin hydrogel and AgNPs-rGO/PDA/GelMA@Gap19 hydrogel were the most significant,indicating that AgNPs-rGO/PDA/GelMA@Gap19 hydrogel,as a new type of pulp capping material,has an obvious antibacterial effect.

Objective This study aims to explore the efficacy and complication rates of the transcranial approach(TCA)and extended endoscopic endonasal approach(EEEA)for the treatment of craniopharyngiomas based on the QST classification,providing a scientific reference for clinical decision-making on surgical approach.Methods A total of 151 patients who underwent craniopharyngioma surgery at our center from January 2018 to December 2023 were enrolled.The patients were categorized into Q-CP(suprasellar type),S-CP(infundibular type),and T-CP(tuberal type)according to the QST classification.Systematic collection and analysis were performed on the outcomes of TCA and EEEA treatments,respectively.The differences in effectiveness between the two approaches were evaluated based on the QST classification.Results The improvement rate of visual symptoms was overall higher in the EEEA group than in the TCA group(59.1%vs.36.5%,P=0.006),and the visual deterioration rate was lower(3.0%vs.14.1%,P=0.006).However,the incidence of cerebrospinal fluid leakage was higher in the EEEA group(15.2%vs.3.5%,χ2=4.986,P=0.026).The incidence of postoperative seizures(8.2%vs.0,P=0.019),brain contusions(10.6%vs.0,P=0.005),and subdural hematoma(9.4%vs.0%,P=0.01)was higher in the TCA group.For patients with Q-CP type,the EEEA group had a higher rate of total tumor resection(92.9%vs.65.2%,P=0.025)and a lower recurrence rate(3.6%vs.21.7%,P=0.047),with shorter hospital stays and lower postoperative costs.The TCA group had higher intraoperative blood loss in this type(300 mL vs.200 mL,Z=-2.261,P=0.024).For S-CP type patients,the EEEA group showed a higher rate of total tumor resection(91.3%vs.74.2%)and a lower recurrence rate(0 vs.12.9%,P=0.031),with lower postoperative hospital costs.In T-CP type,due to the deeper location,EEEA showed limitations in protecting hypothalamic function and the TCA group had a better postoperative hypothalamic function score(P=0.035).Conclusion Based on QST classification,EEEA has advantages in Q-CP and S-CP types and is recommended as the preferred surgical procedure;In the T-CP type,TCA surgery is more helpful in protecting hypothalamic function.

BACKGROUND:Titanium surface micro-nano structure modification is a hot research field in titanium implant surface treatment.The diabetic hyperglycemia environment will affect the stable bonding between titanium implant and bone tissue,so it is necessary to explore the surface micro-nano structure modification to improve the osteogenic activity of titanium implant in high glucose environment.OBJECTIVE:To investigate the effect of gold nanoparticle@mesoporous silica nanoparticles(AuNPs@MSNs)coating on osteogenic activity of osteoblasts under high glucose in vitro.METHODS:Gold nanoparticle suspension and mesoporous silica were prepared respectively,and the two were mixed in deionized water in a certain proportion to prepare gold nanoparticle@mesoporous silica suspension.Titanium sheets were taken and divided into three groups for treatment:the smooth group was treated with water sandpaper;the nanotube group was treated with water sandpaper and then anodized to prepare titanium dioxide nanotube coating,and the experimental group prepared titanium dioxide nanotube coating and then immersed in gold nanoparticle@mesoporous silica suspension to prepare gold nanoparticle@mesoporous silica nanoparticles coating.The microscopic morphology and hydrophilicity of the surface of the three groups of titanium sheets were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets.Cell proliferation was detected by cell live/dead fluorescence staining and CCK-8 assay.Cell adhesion was detected by DAPI/phalloidin staining.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets,and high-glucose osteogenic induction medium was added for culture.Osteogenic differentiation was detected by alkaline phosphatase and Alizarin Red S staining.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the titanium sheet in the smooth group was uniform and flat.The titanium dioxide nanotube arrays in the nanotube group were closely arranged on the surface,and the titanium sheet in the experimental group was loaded with gold nanoparticle@mesoporous silica on the surface and inside of the titanium dioxide nanotubes.The hydrophilicity of the titanium sheets in the nanotube group and the experimental group was better than that in the smooth group.(2)The results of cell live/dead fluorescence staining exhibited that the cell viability on the surface of the three groups of titanium sheets was higher than 90%.The results of CCK-8 assay show that the cell proliferation rate in the experimental group was higher than that in the smooth group and the nanotube group.The results of DAPI/phalloidin staining showed that the titanium dioxide nanotube coating and the gold nanoparticle@mesoporous silica nanoparticles coating were more conducive to cell adhesion.(3)The results of alkaline phosphatase and Alizarin Red S staining showed that the alkaline phosphatase activity and extracellular matrix mineralization of the cells on the titanium sheet surface in the experimental group were higher than those in the smooth group and the nanotube group.(4)The results show that the gold nanoparticle@mesoporous silica nanoparticles coating can enhance the biological activity of the titanium surface and promote osteogenic differentiation in a high glucose environment.