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

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.

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 To explore the sleep quality and mental fatigue level in elderly patients with cerebrovascular small disease(CSVD).Methods A total of 222 patients aged over 65 years old hospitalized due to chronic diseases in Department of Neurology of the Affiliated Jiangning Hospi-tal of Nanjing Medical University from August 2022 to June 2024 were recruited prospectively and continuously.According to the CSVD score,they were divided into a CSVD group(CSVD score≥1,148 cases)and a non-CSVD group(CSVD score=0,74 cases).All the patients were evaluated by sleep quality,fatigue and neuropsychological scale when they were fully cooperated and in good condition.Subsequently,the patients in the CSVD group were further assigned into a good sleep subgroup(117 cases)and a poor sleep subgroup(31 patients).Results The CSVD group had significantly higher total score of Pittsburgh sleep quality index(PSQI),sleep quality score,sleep disturbance score,total score of self-rating fatigue,and mental fatigue score than the non-CSVD group(P＜0.01).The sleep quality score,sleep disturbance score,and mental fatigue score were risk factors for CSVD(P＜0.05).The mental fatigue score was significantly higher in the CSVD patients with poor sleep than those with good sleep(4.13±1.15 vs 2.50±1.92,P＜0.01).Conclusion Elderly CSVD patients were more likely to have decreased sleep quality and mental fatigue,and among them,those with poor sleep quality are prone to having mental fatigue than those with good sleep.

Objective:To observe the effect of moxibustion on angiogenesis-related indicators in knee joint synovial tissue of adjuvant arthritis model rats,and to explore the mechanism of moxibustion in inhibiting vascular endothelial growth factor(VEGF)expression in synovial tissue and further limiting the activation of Rho family proteins Rac1 and Cdc42,thereby inhibiting angiogenesis during rheumatoid arthritis(RA)treatment.Methods:Forty-eight male Sprague-Dawley rats were equally divided into a normal group,a model group,a moxibustion group,and a moxibustion+VEGF agonist group according to the random principle.The complete Freund's adjuvant method was used for modeling.On the 12th day after modeling,the moxibustion group and the moxibustion+VEGF agonist group were subjected to suspended moxibustion at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 20 min each time,once a day,for a total of 15 times.The moxibustion+VEGF agonist group received VEGF agonist(tirofiban hydrochloride hydrate)injection in the knee joint cavity at the same time.Hematoxylin-eosin staining was used to evaluate the pathological changes of rat synovial tissue in each group.Immunohistochemistry was used to observe the CD31 expression level in rat synovial tissue.Western blotting was used to detect the levels of VEGF,Rac1,and Cdc42 protein in rat synovial tissue,and polymerase chain reaction(PCR)was used to detect the VEGF mRNA expression.Results:Compared to the normal group,the expression levels of CD31 protein and VEGF mRNA and protein in rat synovial tissue in the model group increased significantly(P<0.01),and the expression levels of phospho-Rac1 and phospho-Cdc42 proteins also increased significantly(P<0.01).After moxibustion intervention,the expression levels of CD31 protein and VEGF mRNA and protein in the moxibustion group were significantly lower than those in the model group(P<0.01),while the differences in each indicator between the moxibustion+VEGF agonist group and the model group were not statistically significant(P>0.05).Compared to the moxibustion group,the expression levels of CD31 protein,VEGF mRNA and protein,phospho-Cdc42,and phospho-Rac1 in the moxibustion+VEGF agonist group increased significantly(P<0.01).Conclusion:Moxibustion improved synovial inflammation in RA by inhibiting angiogenesis.The mechanism may be to regulate angiogenesis-related VEGF,restrict the activation of Rac1 and Cdc42,and inhibit pseudopodia formation in vascular endothelial cells,thereby reducing angiogenesis.

Objective:To present the epidemiological characteristics of ≤28 days case fatality in both hemorrhagic stroke (HS) and ischemic stroke (IS) patients in national cardiovascular disease surveillance areas from 2015 to 2019.Methods:Data on all new patients with stroke and ≤28 days outcomes from 2015 to 2019 were from the China Registry of Cardiovascular Events, which was established in 2014, covering 100 counties (cities, districts) in 31 provinces in China. Poisson regression was used to analyze the annual trend of ≤28 days case fatality. The age-standardized case fatality was directly calculated based on all new stroke onset.Results:In total, 112 069 deaths in HS patients ≤28 days after the onset, as well as 94 373 in IS patients, were identified during the study period. In 2019, the ≤28 days case fatality rate in HS patients was 4.75 times that of IS patients (37.08% vs. 7.80%), as well as that 4.06 times in urban areas (30.13% vs. 7.43%) and 5.30 times in rural areas (42.63% vs. 8.05%), respectively. Thus, in rural areas, HS patients showed 41.49% higher ≤28 days case fatality rate than that in urban areas, as well as 8.34% higher in IS patients. Those ≤28 days case fatality in both stroke subtypes onset increased with age and reached the highest level in those aged 85 years and over. During the study period, HS and IS patients in each age group displayed significant decrease trend in ≤28 days case fatality rate (trend P<0.001). Compared with that in 2015, the age-standardized ≤28 days case-fatality in HS patients in 2019 decreased by 28.52%, which was more in urban areas (-34.27%) than that in rural areas (-23.19%). Meanwhile, IS patients experienced a 39.90% reduction in ≤28 days case fatality, which was much lower in urban areas (-31.62%) than in rural areas (-45.10%, all trend P<0.001). Conclusions:From 2015 to 2019, ≤28 days case fatality in both HS and IS patients decreased in China. Wide variations of ≤28 days case-fatality were evident in the level and trend in stroke subtype, age of patients, as well as urban and rural areas. More precise and comprehensive strategies for stroke prevention, treatment, and post-stroke management are urgently required in China.

Objective:To explore the surgical strategies and clinical efficacy of open partial nephrectomy in the treatment of renal angiomyolipoma (AML) with inferior vena cava tumor thrombus.Methods:A retrospective analysis was conducted on the clinical data of 5 patients with renal AML and inferior vena cava tumor thrombus who underwent partial nephrectomy at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to December 2022. There were 2 male and 3 female patients, with a median age of 37 years, ranged from 33 to 45 years. All patients were identified during routine physical examinations. Four patients presented with right-sided lesions, while one had a left-sided lesion. The diameter of the primary tumor within the kidney ranged from 3.0 to 7.0 cm, with a median diameter of 5.5 cm.The length of the tumor thrombus within the inferior vena cava ranged from 1.0 to 6.0 cm, with a median length of 1.5 cm. Among them, 2 patients underwent laparoscopic nephrectomy combined with extracorporeal workbench tumor resection and autologous kidney transplantation (the workbench surgery group), while 3 patients underwent open in-situ partial nephrectomy combined with removal of inferior vena cava tumor thrombus (the in-situ nephron-sparing surgery group). The surgical method of the workbench surgery group: The patients first underwent laparoscopic nephrectomy on the affected side combined with inferior vena cava tumor thrombus removal, then the incision was extended to remove the affected kidney, and table partial nephrectomy was performed. After completely removing the tumor and tumor thrombus within the affected kidney and renal vein, autologous kidney transplantation was performed in the iliac fossa. The surgical method of the in-situ kidney preservation surgery group: The affected kidney, renal artery and vein on the affected side, inferior vena cava, and contralateral renal vein were dissected and exposed. The distal end of the inferior vena cava, the contralateral renal vein, the proximal end of the inferior vena cava, and the renal artery on the affected side were blocked respectively. The venous wall was opened in the middle of the renal vein, and the tumor thrombus was gradually pulled out. According to the pre-marked tumor boundary, the tumor within the kidney was gradually removed by alternate blunt and sharp dissection combined with suction, and the wound surface was sutured layer by layer. The perioperative conditions, complications, and follow-up results of the patients were analyzed.Results:All 5 surgeries were successfully completed, with a median operation time of 100 to 450 minutes and a median operation time of 200 minutes. The intraoperative bleeding volume was 100 to 600 ml, with the median of 150 ml. In the in-situ nephron-sparing surgery group, the renal artery occlusion time was 28 to 41 minutes, and the median occlusion time was 34 minutes. All patients were discharged safely after surgery, and there were no serious perioperative complications. The postoperative pathology of all 5 patients was renal angiomyolipoma, without any epithelioid components. The patients were followed up for 12 to 90 months, with a median follow-up duration of 24 months. None of the 5 patients had tumor recurrence or metastasis, and no patient developed chronic kidney dysfunction during follow-ups.Conclusions:Renal AML with venous tumor thrombus is a challenging clinical problem. In situ open partial nephrectomy or the combined approach through the workbench and autologous kidney transplantation can effectively remove the tumor thrombus and maximize the protection of renal function. For cases of ① multiple or complex renal AML; ② complex vascular system structure within the renal sinus requiring precise anatomy; ③ renal AML with a previous history of hemorrhage, complex adhesions around, and difficult dissociation, table partial nephrectomy combined with inferior vena cava tumor thrombus removal and autologous kidney transplantation can be selected. For cases where the expected surgical operation is simple, in situ open partial nephrectomy can significantly shorten the operation time and reduce surgical trauma.

Objective:To analyze the characteristics and changes in incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents from 2015 to 2019.Methods:The incidence and mortality data of ischemic and hemorrhagic stroke from 2015 to 2019 were collected from the China Registry of Cardiovascular Events (China RACE), which was established in 2014 and covered 100 counties (cities and districts) in 31 provinces in China. The age-standardized incidence rate (ASIR) was calculated using the Seventh National Census data as the standard population. The ratio of the incidence rate of ischemic stroke to hemorrhagic stroke was calculated. The subtype-specific mortality-to-incidence ratio (M/I) was calculated by the ratio of the number of deaths to the reported incidence cases. The relative ratio (RR) of M/I for ischemic to hemorrhagic stroke was calculated. The Joinpoint model was used to analyze the annual percentage change (APC) and trend of the incidence rate of stroke.Results:From 2015 to 2019, a total of 1 354 614 new stroke cases were reported, including 1 077 244 (79.52%) ischemic stroke and 277 370 (20.48%) hemorrhagic stroke cases, respectively. A total of 248 620 stroke deaths were reported, including 119 819 (48.19%) ischemic stroke deaths and 128 801 (51.81%) hemorrhagic stroke deaths. The incidence ratio of ischemic/hemorrhagic stroke from 2015 to 2019 was 3.50∶1, 3.76∶1, 3.63∶1, 4.23∶1, and 4.35∶1, respectively. From 2015 to 2019, there was no statistically significant annual trend of ASIR of ischemic stroke in overall, urban and rural areas and males ( Ptrend>0.05), while there was a downward trend in females (APC=-1.02%, Ptrend=0.042). The incidence of hemorrhagic stroke in the whole population, rural areas, males and females showed a downward trend ( Ptrend<0.05). Patients aged 45-49 years had an upward trend in the incidence rate of ischemic stroke (APC=3.82%, Ptrend=0.011), while those aged 70-74 years (APC=-7.37%, Ptrend=0.034), 80-84 years (APC=-9.75%, Ptrend=0.001) and 85 years and over (APC=-11.22%, Ptrend=0.017) presented a downward trend in the incidence of hemorrhagic stroke. During the period, the overall relative ratio of M/I (RR) for ischemic to hemorrhagic stroke was 4.2∶1, which was lower in urban than in rural areas (3.8 vs. 4.3). The largest gap between urban and rural areas was in the 55-59 age group (6.8 vs. 9.3). Conclusion:The incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents are severe from 2015 to 2019, and there are regional and population differences.

Objectives:This study aimed to explore the association between perceived mental stress (MS), lymphocyte subset variations, and coronary lesion severity in patients with coronary artery disease (CAD).Methods:Patients with CAD were enrolled in this study from September 2023 to May 2024. Perceived Stress Scale-14 (PSS-14) was used to evaluate MS during the last 1 month. Lymphocyte subsets were analyzed, including the percentage and absolute counts of CD3 +, CD3 +CD4 +, CD3 +CD8 +, CD3 -CD19 +, CD3 -CD56 +16 +, and the Th/Ts ratio. Statistical analysis was conducted using SPSS 24.0. Results:This study recruited patients with 323 CAD, with an average age of 61 (56, 68) years, including 203 males and 120 females. According to the PSS-14, a score of 14-42 and 43-70 were categorized as normal and increased MS, respectively. Patients with CAD with increased MS had significantly higher Gensini scores than those with normal MS [37(19,64) vs. 28(12,50), Z=-2.19, P=0.029]. Male CAD patients with increased MS exhibited significantly higher Gensini scores [39(20, 58) vs. 26(12, 45), Z=-2.37, P=0.018], levels of CD3 +CD8 +%[28.3%(23.6%,36.6%) vs. 25.9%(21.0%,32.4%), Z=-2.05, P=0.041], and CD3 +CD8 +absolute value [485 (346, 675) vs. 396 (309, 510) cells/μl, Z=-2.55, P=0.011] than those with normal MS. In male patients with CAD, a positive correlation was observed between Gensini scores (correlation coefficient: 0.181, P=0.011), PSS-14 scores, and CD3 +CD8 +absolute value (correlation coefficient: 0.162, P=0.038). Conclusion:This study reveals a positive correlation between MS and coronary stenosis severity, with notable sex differences. In male patients with CAD, higher levels of MS are associated with more severe coronary stenosis. The potential underlying mechanism may involve the regulation of lymphocyte subsets .