Objective: To investigate the association between self-rated health status and mortality risk, and to evaluate the predictive value of self-rated health status for mortality risk among the elderly. Methods: Based on the China Health and Retirement Longitudinal Study (CHARLS) database, data of sociodemographic information, self-rated health status and mortality of the elderly aged 60 years and older were collected from 2011 to 2018. The association between self-rated health status and mortality risk among the elderly was analyzed using a multivariable Cox proportional risk regression model. Results: Totally 4 850 individuals were included, with an median age of 65 (interquartile range, 8) years. There were 2 485 males (51.24%) and 2 365 females (48.76%). There were 877 individuals (18.08%) rated their health as good, 2 078 individuals (42.85%) as general, 1 895 individuals (39.07%) as poor. A total of 28 955 person-years were followed up, with an average follow-up of 5.97 years per person. There were 855 deaths by the end of follow-up in 2018, and the median survival time was 7 (interquartile range, 3) years. Multivariable Cox proportional risk regression analysis showed that there were interactive effects of age, sex and self-rated health status on mortality, respectively (both P<0.05). The results of gender-stratified analysis showed that there was no significant association between self-rated health status and mortality risk in old women (P>0.05). The mortality risk was higher in old men with poor self-rated health than with good self-rated health (<70 years, HR=5.382, 95%CI: 3.263-8.876; 70 to 79 years, HR=3.536, 95%CI: 1.070-11.686; ≥80 years, HR=3.043, 95%CI: 1.827-5.066). Conclusion There is an association between self-rated health status and mortality risk among the elderly, the old men with poor self-rated health had a higher mortality risk.

Inhalation of crystalline silicon dioxide particles can induce silicosis, and the development of silicosis is closely related to the occurrence and development of pulmonary inflammation and pulmonary fibrosis. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome has been established as a major proinflammatory receptor for sensing environmental danger signals. Activation of NLRP3 inflammasomes after phagocytosis of silicon dioxide particles by pulmonary macrophages may be an important mechanism to induce oxidative stress and sustained inflammatory response in the lung. This article summarizes the role of NLRP3 inflammasome in the inflammatory response and pulmonary fibrosis in silicosis, and analyzes it as a potential target for silicosis treatment.

Objective To investigate the characteristics of pulmonary function changes in older children with pertussis.Methods Clinical data and pulmonary function date of older children diagnosed with pertussis in outpatient clinics from April 2021 to December 2023 were collected.The clinical data of the case group were collected.A group of healthy older children were included as the control group.Pulmonary function parameters included peak expiratory flow(PEF),forced expiratory volume in the first second(FEV1),forced vital capacity(FVC),FEV1/FVC,expiratory flow at 50%of vital capacity(FEF50),maximum mid-expiratory flow(MMEF)and expiratory flow rate with 75%vigorous exhalation(FEF75).Results Seventy children(36 boys and 34 girls)with pertussis were recruited in the case group,including 54 children with pertussis only and 16 children with pertussis and asthma together.The incidence of paroxysmal cough was 40.0%(28/70)and inspiratory croup 8.5%(6/70)in the case group.Sixty healthy children(28 boys and 32 girls)were included in the control group.There were no significant differences in gender,age,height and body weight between children with pertussis alone group and the control group(P＞0.05).The pulmonary function parameters were significantly lower in the children with pertussis alone group than those in the control group,and PEF had the most obvious decline:PEF%pred[80.5(62.6,85.9)vs.109.8(103.2,118.7)].Compared with the pertussis alone group,pulmonary function was not decrease further in the pertussis combined with asthma group.After the improvement of clinical symptoms of children in the pertussis alone group,the level of pulmonary function(PEF and FEF50)increased significantly,but they were still lower than those of the control group.Conclusion The pulmonary function declines slightly in loder children with pertussis.The decreased PEF is most significant.

By binding alpha-particle to ligands, targeted alpha-particle therapy illuminates the diseased tissue, using the radiographic energy and the range in the tissues of nuclides, and avoids damage to normal tissue to obtain the expected therapeutic effect, which is mainly used for tumor treatment. Targeted ligands are ideal drug carriers to deliver alpha-particle to the target to kill tumor cells accurately. In recent years, there have been some progresses in the research of α-radionuclide drug-based targeted ligands in nanomaterials, which have improved drug delivery and off-target effects. By summarizing the current research status, it is expected to provide reference for the development of alpha-particle drug delivery in the industry.

Inhalation of crystalline silicon dioxide particles can induce silicosis, and the development of silicosis is closely related to the occurrence and development of pulmonary inflammation and pulmonary fibrosis. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome has been established as a major proinflammatory receptor for sensing environmental danger signals. Activation of NLRP3 inflammasomes after phagocytosis of silicon dioxide particles by pulmonary macrophages may be an important mechanism to induce oxidative stress and sustained inflammatory response in the lung. This article summarizes the role of NLRP3 inflammasome in the inflammatory response and pulmonary fibrosis in silicosis, and analyzes it as a potential target for silicosis treatment.

Objective:To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity.Methods:The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity.Results:Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation ( P＜0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells ( P＜0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group ( P＜0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group ( P＜0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group ( P＜0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group ( P＜0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group ( P＜0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group ( P＜0.05). Conclusion:Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.

Background::Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-na?ve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-na?ve MM.Methods::This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-na?ve MM patients.Results::A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-na?ve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG +Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-na?ve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-na?ve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-na?ve MM patients. Conclusions::Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Objective:To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity.Methods:The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity.Results:Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation ( P＜0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells ( P＜0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group ( P＜0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group ( P＜0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group ( P＜0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group ( P＜0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group ( P＜0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group ( P＜0.05). Conclusion:Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.

Objective:To explore the current status of intrinsic capacity in elderly patients with hospitalization-associated disability (HAD) and explore its influencing factors.Methods:From November 2023 to January 2024, convenience sampling was used to select 203 elderly patients with HAD at Xuanwu Hospital of Capital Medical University as the study subjects. A survey was conducted on elderly patients using the General Information Questionnaire, Fried Frailty Phenotype, Barthel Index, Social Support Rating Scale, and Intrinsic Capacity Assessment Tool. Binomial Logistic regression was used to analyze the influencing factors of intrinsic capacity in elderly patients with HAD.Results:A total of 203 questionnaires were distributed, and 199 valid questionnaires were collected, with a valid response rate of 98.03% (199/203). The total score of intrinsic capacity in 199 elderly patients with HAD was 5.00 (4.00, 6.00), with scores for cognitive dimension, psychological dimension, motor dimension, vitality dimension, and sensory dimension being 1.00 (1.00, 2.00), 2.00 (1.00, 2.00), 0 (0, 1.00), 1.00 (1.00, 1.00) and 1.00 (1.00, 1.00), respectively. The binomial Logistic regression showed that department of medicine and surgery, self-rating health status, social support, serum albumin, and Barthel Index were the influencing factors of intrinsic capacity in elderly patients with HAD ( P<0.05) . Conclusions:The intrinsic capacity of elderly patients with HAD is at medium to low level, with the most severe impairment in the motor dimension. Medical and nursing staff should develop personalized rehabilitation measures for elderly HAD patients based on the influencing factors of their intrinsic capacity, enhance their intrinsic capacity, and reduce the burden of care on families and society.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.