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

Objective:To conduct a systematic review of reported cases of autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by uromodulin ( UMOD) gene mutations (ADTKD- UMOD) in China, summarize the clinical, pathological and genetic variation characteristics, and analyze the genotype-phenotype correlation. Methods:It was a retrospective systematic analysis study. The search terms "UMOD", "ADTKD-UMOD", "uric acid kidney disease (UAKD)", "medullary cystic kidney disease type 2 (MCKD2)", and "familial juvenile hyperuricemic nephropathy type 1 (FJHN1)" were used, and relevant literature on ADTKD- UMOD cases in China were retrieved from PubMed, CNKI, Wanfang Data and Chinese Medical Journal Full-text Database. The data of the cases involved in the literature were collected and summarized, and the clinical and pathological characteristics and genetic variation features of Chinese ADTKD- UMOD patients were analyzed. The patients were divided into exon 3 mutation group and non-exon 3 mutation group based on the mutation sites, and the differences of clinical phenotypes between the two groups were compared. The patients were also divided into domain 8 cysteine (D8C) mutation group and non-D8C mutation group based on the mutation regions, and the differences of clinical phenotypes between the two groups were compared. Results:A total of 17 relevant articles on ADTKD- UMOD cases in China were retrieved, involving 57 patients from 34 families. The age at first diagnosis was 24.0 (20.0, 39.5) years. Fifty-three patients (93.0%) had a family history of nephropathy or hyperuricemia. Among the 48 patients with recorded blood uric acid levels, 36 patients (75.0%) had hyperuricemia, with age of 24.0 (20.3, 37.3) years. Fifty-four patients had chronic kidney disease assessment records, among which 46 patients (85.2%) developed chronic kidney disease, and 21 patients (38.9%) developed end-stage renal disease. The age of end-stage renal disease was 39.0 (24.0, 46.0) years, with age of 33.0 (21.0, 46.5) years in males and 39.5 (25.5, 45.5) years in females ( Z=-0.649, P=0.516). Twenty patients underwent renal biopsies, and 19/20 patients had tubular or interstitial lesions, and 9/20 patients had glomerular lesions, mainly manifested as focal segmental or global glomerulosclerosis. Forty patients had renal ultrasound examination records, among which 36 patients (90.0%) had abnormal results, with renal cysts being the most common type (12 patients, 30.0%). Among the 34 family cases, no ADTKD- UMOD hotspot mutation was found in the UMOD gene mutations. Thirty-two families (94.1%) were missense mutations, 26 families (76.5%) had mutation sites in exon 3, and 16 families (47.1%) had mutation regions in D8C. The proportion of hypertension in the non-exon 3 mutation group was higher than that in the exon 3 mutation group ( χ2=9.84, P=0.002). The proportion of males in the non-D8C mutation group was higher than that in the D8C mutation group ( χ2=4.97, P=0.026). Conclusions:The main clinical manifestations of Chinese ADTKD- UMOD patients are hyperuricemia, and the main renal histopathological changes are tubular and interstitial lesions. Some patients have glomerular lesions, which need to be differentiated from focal segmental glomerulosclerosis. Renal cysts detected by renal ultrasound can suggest the diagnosis of the disease. Missense mutation is the main type of UMOD gene mutations. The gene mutation region may be correlated with hypertension and gender.

Objective:To define the concept of proactive health behavior.Methods:Literature related to proactive health behavior was retrieved from China National Knowledge Infrastructure, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Embase, and Ovid databases, with a retrieval time frame from database inception to March 1, 2025. Walker and Avant's concept analysis method was used to analyze the concept of proactive health behavior.Results:A total of 46 articles related to proactive health behavior were included. Proactive health behavior encompasses five key attributes: self-initiation, long-term persistence, multidimensional integration, future orientation, and overcoming barriers. Antecedents include individual factors, supportive factors, and environmental factors. Outcomes include promoting individual health and improving quality of life, enhancing personal health literacy, reducing disease burden, and fostering a proactive health atmosphere.Conclusions:The concept attributes of proactive health behavior were clarified through concept analysis. Future researchers may develop proactive health behavior assessment tools and construct intervention strategies based on their connotation.

Objective:To investigate the association of monocyte-to-high-density lipoprotein cholesterol ratio (MHR) with the severity of white matter hyperintensities (WMHs) and its spatial distribution.Methods:Patients admitted to the Department of Neurology, Jiangning Hospital Affiliated to Nanjing Medical University due to various chronic diseases or physical examinations between January 2023 and December 2024 were included retrospectively. Past medical history, clinical and imaging data were collected. The Fazekas scale was used to assess the severity of WMHs. According to the scoring results of periventricular WMHs (PVWMHs) and deep WMHs (DWMHs), WMHs were divided into no/mild group (0-1 points) and moderate/severe group (2-3 points). Multivariate logistic regression analysis was used to determine independent correlation factors for the severity of WMHs, PVWMHs, and DWMHs. Results:A total of 357 patients were included, aged 65.42±9.95 years, with 198 males (55.5%). There were 193 patients (54.1%) in the no/mild group and 164 (45.9%) in the moderate/severe group. Univariate analysis showed that the proportion of patients with hypertension, diabetes, history of cerebral infarction and cerebral hemorrhage, carotid plaque, and age, serum creatinine, monocyte count and MHR in the moderate/severe group were significantly higher than those in the no/mild group (all P<0.05). Multivariate logistic regression analysis showed a significant positive correlation between MHR and the severity of WMHs (odds ratio 3.138, 95% confidence interval 1.042-9.451; P=0.042). Further analysis showed a significant positive correlation between MHR and PVWMHs (odds ratio 3.384, 95% confidence interval 1.111-10.305; P=0.032), but no independent correlation with DWMHs. In addition, age and hypertension, diabetes, history of cerebral infarction and cerebral hemorrhage were significantly positively correlated with the severity of WMHs, PVWMHs and DWMHs. Conclusion:MHR is correlated with the severity of WMHs, and higher MHR is significantly associated with PVWMHs, but not with DWMHs.

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 investigate the effect of resveratrol on the proliferation,apoptosis,and migration of breast cancer cells and its mechanism and correlation with immune cell infiltration.Methods The network pharmacology and bioinformatics(GEPIA and KM-PLOT databases)were used to predict the target genes of breast cancer regulated by resveratrol,and their expression levels in breast cancer and correlations with immune cell infiltration were verified.The effects of resveratrol on the proliferation,cell cycle and apopto-sis,and migration of breast cancer cells were determined by the CCK-8 assay,flow cytometry,and cell scratch test,respectively.The mRNA expression levels of related target genes were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Pearson correlation analysis was used to analyze the correlations of the expression levels of related genes with immune cell infiltration.Results The expression levels of TP53 and VEGFA genes in breast cancer tissues were significantly higher than those in normal tissues(Z=-4.181 and-8.763,P＜0.05).In the GEPIA database,the expression level of CDKN1A gene in breast cancer tis-sues was significantly higher than that in normal tissues(Z=-2.135,P＜0.05).In the KMPLOT database,the expression level of HIF1α gene in breast cancer tissues was significantly higher than that in normal tissues(Z=-2.269,P＜0.05).Pearson correlation a-nalysis showed that the expression level of TP53 gene was positively correlated with B cell infiltration(partial.cor=0.102,P＜0.01).The expression level of HIF-1α was positively correlated with the infiltration of CD8+T cells,CD4+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.39,0.159,0.284,0.325,and 0.294,P＜0.01).The expression level of VEGFA gene was positive-ly correlated with neutrophil infiltration(partial.cor=0.141,P＜0.01).The expression level of CDKN1A gene was positively correlated with the infiltration of CD8+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.081,0.209,0.11,and 0.09,P＜0.01).Resveratrol could inhibit the proliferation of breast cancer cells,and the IC50 and IC25 values of breast cancer cells were 150 μmol/L and 50 μmol/L,respectively,after 48 hours of treatment with resveratrol.In addition,resveratrol could also arrest breast cancer cells in G1 phase,induce their apoptosis,and inhibit their migration.After treating breast cancer cells with resveratrol for 24 hours,with the increase of resveratrol concentration from 50 μmol/L to 150 μmol/L,the mRNA expression levels of TP53 and HIF1α genes increased gradually,with a significant difference between the two groups(P＜0.05).After treating breast cancer cells with res-veratrol for 48 hours,the expression level of VEGFA mRNA was significantly decreased,and there was a significant difference between the two groups(P＜0.05).Conclusion TP53,HIF-1α,VEGFA,and CDKN1A genes are the action targets of resveratrol in breast cancer,which are mainly involved in the regulation of immune cell infiltration in breast cancer.Resveratrol inhibits the proliferation of breast cancer cells,induces cell cycle arrest and apoptosis,and inhibits cell migration by regulating the P53-HIF1α/CDKN1A-VEGFA signaling pathway.

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.

Objective:To define the concept of proactive health behavior.Methods:Literature related to proactive health behavior was retrieved from China National Knowledge Infrastructure, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Embase, and Ovid databases, with a retrieval time frame from database inception to March 1, 2025. Walker and Avant's concept analysis method was used to analyze the concept of proactive health behavior.Results:A total of 46 articles related to proactive health behavior were included. Proactive health behavior encompasses five key attributes: self-initiation, long-term persistence, multidimensional integration, future orientation, and overcoming barriers. Antecedents include individual factors, supportive factors, and environmental factors. Outcomes include promoting individual health and improving quality of life, enhancing personal health literacy, reducing disease burden, and fostering a proactive health atmosphere.Conclusions:The concept attributes of proactive health behavior were clarified through concept analysis. Future researchers may develop proactive health behavior assessment tools and construct intervention strategies based on their connotation.

Objective To analyze the influencing factors of health behaviors in stroke patients,and explore the chain mediating effects of self-efficacy and e-health literacy between the perception of stroke recurrence risk and health behaviors in stroke patients,providing a reference for strengthening the health behavior and reducing recurrence risk in stroke patients.Methods 249 stroke patients were selected as the research objects from March to September 2024 in a tertiary hospital in Shanghai,China.Patients were surveyed using General Information Questionnaire,Stroke Recurrence Risk Perception Scale,Stroke Health Behavior Scale(HBS-SP),Chronic Disease Self-Efficacy Scale(CDSES),and the e-health Literacy Scale(e-HEALS).Pearson correlation analysis was used to explore the correlations among various variables,and SPSS 26.0 software macro program Process Model 6 was used to conduct chain mediation model test.Results The scores of Recurrence Risk Perception,HBS-SP,CDSES and e-HEALS of stroke patients were(42.88±6.48)scores,(68.32±14.13)scores,(6.87±1.55)scores and(27.76±6.06)scores,and all the variables were positively correlated(P<0.01).The mediating effect model showed that self-efficacy and e-health literacy played a chain mediating role in the recurrence risk perception and health behavior in stroke patients,with an effect size of 0.488,accounting for 37.22%of the total effect.Conclusions The recurrence risk perception and health behavior of stroke patients are both at a moderate level.In the future,we can establish a mobile management platform to provide comprehensive health management for stroke patients.Further exploration of strategies to enhance stroke patients'self-efficacy and channels for online health education could be pursued to improve their health behaviors.

Programmed cell death is an important defense mechanism of the body, which monitors internal lesions and defends external infections to maintain the stability of the body.In the past, there were two main types of cell death: apoptosis and necrosis.With the development of scientific research, new cell death modes, such as pyroptosis and ferroptosis, have attracted much attention and are involved in the occurrence and development of diabetic retinopathy (DR).Many pathogenic factors, such as oxidative stress, hyperglycemia and inflammation, lead to the death of retinal cells in different ways, such as apoptosis, pyroptosis and ferroptosis.Apoptosis is the earliest pathological response of DR, which occurs at the initial stage of oxidative stress, and the integrity of cell membranes is maintained at the early stage of apoptosis.Apoptotic cells are cleared by phagocytes in the tissue before dissolution, which avoids unnecessary inflammation.Pyroptosis is activated by Caspase-1, then cleaves GSDMD, which can lead to pore formation and osmotic cell lysis, resulting in inflammation and immune response.Ferroptosis involves lipid peroxidation and abnormal iron homeostasis.Lipid peroxidation and glutathione depletion are the main markers of ferroptosis.The three cell death modes are independent and interrelated, and play a role in the occurrence and development of diseases together with other cell death modes.This article reviews the current status of cell apoptosis, pyroptosis and ferroptosis in DR.