Objective To investigate the effects of hypoxia on the transcriptional phenotype and ultrastructure of tumor-associated macrophages(TAMs)in glioma.Methods CD14+monocytes were isolated from healthy human peripheral blood samples collected from the Blood Bank of the First Affiliated Hospital of Army Medical University,and the cells were induced to differentiate into TAMs through co-culture with glioma cell-conditioned medium.Hypoxic TAM models were established using varying concentrations of cobalt chloride hexahydrate(CoCl2,50～400 μmol/L)or hypoxic conditions(1%,5%,10%O2)for 48 h,while normoxic TAM models(21%O2)served as controls.RT-qPCR and transcriptome sequencing were employed to analyze transcriptional changes in TAMs under normoxic and hypoxic conditions.Gene set enrichment analysis(GSEA)was applied to compare the differences in angiogenesis,glycolysis and other hypoxia-responsive pathways between the 2 conditions.Transmission electron microscopy(TEM)or immunofluorescence staining was conducted to assess the ultrastructural alterations in cytoskeleton,endoplasmic reticulum(ER),and mitochondria in normoxic and hypoxic TAMs(1%O2).Results Hypoxic TAMs exhibited up-regulated transcription of hypoxia-responsive markers(oxygen transport,glycolysis,pro-angiogenesis),with the effects correlating with hypoxia severity(P<0.05).GSEA revealed significant up-regulation of hypoxia,angiogenesis regulation,glycolysis and gluconeogenesis,and starvation stress pathways,alongside down-regulation of innate immunity,macrophage activation,cytoskeleton,and protein maturation pathways in hypoxic TAMs(P<0.05).TEM and immunofluorescence staining demonstrated obvious ultrastructure changes,including disrupted cytoskeletal organization,shortened rough ER with reduced ribosomes,mitochondrial swelling with cristae damage,and diminished ER-mitochondria contacts in hypoxic TAMs.Conclusion CoCl2 and hypoxia induce a hypoxic transcriptional phenotype in TAMs,which may potentially associated with ultrastructural remodeling of the cytoskeleton,ER,and mitochondria.

Objective:To investigate dietary patterns of individuals aged ≥50 in Shanghai and analyze their association with frailty.Methods:Using data from the third wave of the Study on Global Ageing and Adult Health in Shanghai conducted between 2018 and 2019. We collected the frequency and average intake of food by the food frequency questionnaire. Factor analysis was used to extract dietary patterns, and a frailty index was constructed using the ratio of the cumulative total score of health deficits to 35 health-related variables considered. We used an ordinal multinomial logistic regression model to analyze the association between dietary patterns and frailty.Results:A total of 3 274 participants aged (67.9±9.2) years were included in the study, including 1 971 (60.2%) men and 1 303 (39.8%) women. We extracted four dietary patterns: high-protein-nuts pattern, potato-bean-vegetable-fruit pattern, poultry-meat pattern, and high-oil-salt pattern. After adjusting for confounding factors, the logistic regression analysis showed that compared with the high-oil-salt pattern, the high-protein-nuts pattern was negatively associated with the risk of higher frailty ( OR=0.743, 95% CI: 0.580-0.951). We did not find an association between dietary patterns and frailty between the different gender groups. In the age group 50-64, the high-protein-nuts and potato-bean-vegetable-fruit patterns were negatively correlated with a higher degree of frailty than the high-oil-salt pattern. In the low-level physical activity group, the high-protein-nuts pattern was negatively correlated with a higher degree of frailty than the high-oil-salt pattern ( OR=0.509, 95% CI: 0.361-0.720). However, we found no significant effect of the high-protein nuts pattern, potato-bean-vegetable-fruit pattern, and poultry-meat pattern on the risk of higher frailty compared to the high-oil-salt pattern in the moderate to high level of physical activity group. Conclusions:Compared to the high-oil-salt pattern, dietary patterns with a higher intake of high-protein nuts, potatoes, legumes, and fruits and vegetables might be associated with a lower risk of higher frailty in residents aged 50-64 years of age than with a high oil and salt pattern. At the same time, it may have a more significant protective effect in people with lower physical activity levels. It is suggested that a diet rich in high-protein foods, nuts, potatoes, beans, vegetables, and fruits may help reduce and delay the risk of frailty.

Objective:To understand the association between vitamin D level and grip strength in people aged ≥50 years in Shanghai.Methods:Data were obtained from the WHO's Study on Global Ageing and Adult Health in Shanghai during 2018-2019. Logistic regression model was used to analyze the association between vitamin D level and grip strength, and a stratified analysis was conducted for different gender, age and dairy product intake groups. Restricted cubic spline was used to evaluate the dose-response association between vitamin D level and low grip strength.Results:A total of 4 391 participants were included in the study, including 2 054 men (46.8%), with an average age of (67.02±8.81) years. And 1 421 individuals (32.4%) had low grip strength; 1 533 individuals (34.9%) had vitamin D deficiency, and 401 individuals (9.1%) had vitamin D deficiency. After adjusted for confounding factors, the logistic regression results analysis showed that individuals with vitamin D deficiency had a higher risk for low grip strength ( OR=1.41, 95% CI: 1.09-1.83). In men, after adjusting for confounding factors, vitamin D deficiency was positively associated with the risk for low grip strength ( OR=1.67, 95% CI: 1.12-2.50), but there was no significant association between vitamin D level and grip strength in women ( OR=1.30, 95% CI: 0.97-1.74). In age group 60-69 years and ≥80 years, there was significant association between vitamin D deficiency and low grip strength after adjusting for confounding factors ( OR=1.57, 95% CI: 1.05-2.35; OR=2.40, 95% CI: 1.08-5.31). In people who had daily intake of dairy product <250 ml, there was positive association between vitamin D deficiency and low grip strength, but there was no significant association in people who had daily dairy product ≥250 ml after adjusting for confounding factors. The restrictive cubic spline demonstrated that risk of low grip strength might decreased with the increase of vitamin D levels, however, the difference was not significant ( P>0.05). Conclusions:This study demonstrated that there is association between vitamin D level and grip strength. People with vitamin D deficiency have higher risk for low grip strength.

This study was aimed to investigate the effect of hypoxia on lipopolysaccharide (LPS)-induced CXC-chemokine ligand-10 (CXCL10) expression and the underlying mechanism. C57BL/6J mice were randomly divided into control, hypoxia, LPS, and hypoxia combined with LPS groups. The LPS group was intraperitoneally injected with 0.5 mg/kg LPS, and the hypoxia group was placed in a hypobaric hypoxia chamber (simulated altitude of 6 000 m). The serum and hippocampal tissue samples were collected after 6 h of the treatment. The levels of CXCL10 in the serum and hippocampal tissue of mice were detected by ELISA. The microglia cell line BV2 and primary microglia were stimulated with hypoxia (1% O₂) and/or LPS (100 ng/mL) for 6 h. The mRNA expression level of CXCL10 and its content in culture supernatant were detected by real-time quantitative PCR and ELISA, respectively. The phosphorylation levels of nuclear factor κB (NF-κB) signaling pathway-related proteins, p65 and IκBα, were detected by Western blot. Moreover, after NF-κB signaling pathway being blocked with a small molecular compound, PDTC, CXCL10 mRNA expression level was detected in the BV2 cells. The results showed that in the LPS-induced mouse inflammatory model, hypoxia treatment could promote LPS-induced up-regulation of CXCL10 in both serum and hippocampus. Compared with the cells treated with LPS alone, the expression of CXCL10 mRNA and the content of CXCL10 in the culture supernatant of BV2 cells treated with hypoxia combined with LPS were significantly increased. The CXCL10 mRNA level of primary microglial cells treated with hypoxia combined with LPS was significantly up-regulated. Compared with the cells treated with hypoxia or LPS alone, the phosphorylation levels of p65 and IκBα in the BV2 cells treated with hypoxia combined with LPS were significantly increased. PDTC blocked the induction of CXCL10 gene expression by LPS in the BV2 cells. These results suggest that hypoxia promotes LPS-induced expression of CXCL10 in both animal and cell models, and NF-κB signaling pathway plays an important role in this process.
Animals ; Mice ; Chemokines, CXC/pharmacology* ; Hypoxia ; Ligands ; Lipopolysaccharides/pharmacology* ; Mice, Inbred C57BL ; Microglia/metabolism* ; NF-kappa B/metabolism* ; NF-KappaB Inhibitor alpha/pharmacology* ; RNA, Messenger/metabolism*

Objective: To identify distinct frailty trajectories in a cohort of nationwide community adults aged 50 years and above, and explore the relationship between frailty trajectories and their socioeconomic characteristics and behavioral factors at baseline survey. Methods: Data were from the three waves of "Global Ageing and Adult Health Research" (SAGE) by World Health Organization in China. The frailty index is generated from 32 items. Group-based trajectory modeling using a censored normal model was conducted to identify the patterns in frailty progression over time. Multinomial logistic regression model was used to examine the effect of socioeconomic status and behavioral factors on the frailty trajectories. Results: A total of 4 303 adults aged 50 years and above with complete data from all three rounds of project were included in the final analysis. Three frailty trajectories were identified: low and stable trajectory (LT) (56.8%), moderately increased trajectory (MT) (34.4%) and highly increased trajectory (HT) (8.8%). The results of the multinomial logistic regression analysis showed that the HT group was more likely to be women (OR=1.88, 95%CI:1.22-2.92) and rural residents (OR=1.87, 95%CI:1.29-2.70) compared with the LT group. In terms of household wealth per capita, there was a clear gradient in ORs, the people with lower household wealth were more likely to be classified in the HT group. Conclusion: This study identified three patterns of progression of frailty trajectories in population aged 50 years and above in China and highlighted that interventions should target those vulnerable populations with rapid progression of frailty.
Adult ; Humans ; Female ; Male ; Frailty/epidemiology* ; China/epidemiology* ; Aging ; Logistic Models ; Social Class

Objective: To evaluate the association between grip strength (GS) and cognitive function in a population-based longitudinal cohort of Chinese adults aged ≥50 years. Methods: The study population of 3 600 adults was from the baseline survey and two rounds of follow up of World Health Organization (WHO) study of global ageing and adult health (SAGE) in five districts of Shanghai (Hongkou, Huangpu, Minhang, Qingpu and Pudong) after excluding individuals with self-report stroke and depression. The effects of baseline GS on cognitive function and its changes were evaluated. Factor analysis was applied to generate an overall cognition score based on verbal recall trials, verbal fluency test, forward digit span test and backward digit span test. Linear mixed effects model was used to examine the predictive capability of baseline GS for changes in cognitive function. Results: A total of 3 600 participants aged (61.2±8.1) years at baseline survey were included in this study, including 1 668 (46.3%) men and 1 932 (53.7%) women. The average of baseline GS and total cognitive function score were (28.19±12.18) kg and (58.93±14.56) respectively. Cognitive function score declined significantly during the follow-up, however, the changes were different among different age groups, education level groups and household income groups. After adjusted for age, education level, marital status, household income, co-morbidity of chronic conditions, drinking status, smoking status, physical activity level, vegetable/fruit intakes and BMI, no relationships between the baseline GS and cognitive score at baseline survey and at 1^st follow-up were observed, however, compared with lower GS quartile group, there was a significant relationship between higher baseline GS level and better cognitive function at 2^nd follow-up. The participants with highest GS quartile had better cognitive performance over time (male: β=1.938,95%CI:0.644-3.231,P=0.003, female: β=2.192,95%CI:0.975-3.409,P<0.001 and those aged 50-64 years: β=1.652,95%CI:0.646-2.659,P=0.001) than those with the lowest quartile. Conclusions: Higher baseline GS was significantly related to better cognitive function with slow decline. Thus, it is an indicator of cognitive function in middle-aged and elderly Chinese.
Adult ; Aged ; Middle Aged ; Female ; Humans ; Male ; Prospective Studies ; China/epidemiology* ; Hand Strength ; Cognition ; Educational Status

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.
Female ; Male ; Humans ; Child ; Retrospective Studies ; Osteomyelitis/drug therapy* ; Arthralgia ; Diphosphonates ; Fever ; Graft vs Host Disease

ObjectiveTo analyze the effect of frailty status on the risk of mortality in a community-based population aged 45 years and above in Shanghai with different characteristics， and to provide further basis for population-based interventions for frailty and prevention of adverse outcomes. MethodsData were derived from baseline data from the Shanghai prospective study on AGEing and adult health （2009-2010） and cohort follow-up of causes of death up to October 30， 2021. Frailty index （FI） scores were constructed from 40 variables. Those with frailty index FI≥0.2 were judged to be in a frail state， and a multifactorial Cox regression model was used to calculate the hazard ratio （HR） to evaluate the effect of frailty status on the risk of death in different age groups by gender. Socioeconomic characteristics （age， residence， marital status， education and family economic level， etc.） and health-related behaviors （smoking， alcohol consumption， fruit and vegetable intake， social participation， etc.） were included as control variables. ResultsThe study included 7 978 subjects， 777 （9.7%） of whom were in a frail state. After （11.3±1.8） years of follow-up， 1 043 （13.1%） individuals were dead， including 214 （27.5%） who were frail. The results of the multifactorial Cox regression analysis showed that the effect of frailty on the risk of death in each subgroup was in descending order of men in the middle-aged group （45‒ years） （HR=2.92， 95%CI： 1.38-6.19）， women in the low-aged elderly group （60‒ years） （HR=1.68， 95% CI： 1.08-2.60）， and women in the old-aged elderly group （≥75 years and older） （HR=1.59， 95%CI： 1.22‒2.06）. ConclusionFrailty is associated with the risk of death， and we should focus on the frailty status of men aged 45~59 years and women aged 60 years and above. Early screening and assessment of frailty status and taking appropriate preventive interventions may reduce the occurrence of adverse outcomes and premature death.

Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome